An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of the ABNCoV2 Vaccine in Severe Acute Respiratory Syndrome (SARS) Coronavirus (CoV)-2 Seronegative and Seropositive Adult Subjects
Phase: PHASE2
Conditions: COVID-19 Disease
Sponsor: Bavarian Nordic

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Clinical Trial Protocol
EudraCT # 2021-001393-31
NCT05077267
An Open Label Phase 2 Trial to Evaluate the Safety, 
Tolerability and Immunogenicity of the ABNCoV2 
Vaccine in SARS-CoV-2 Seronegative and Seropositive 
Adult Subjects
15-Oct-2021
ABNCoV2
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Table of Contents 
Table of Contents ...................................................................................................... 2 
List of Tables ............................................................................................................. 6 
List of Figures ........................................................................................................... 6 
1 
General Information ......................................................................................... 7 
1.1 Abbreviation ...................................................................................................... 7 
1.2 Definitions .......................................................................................................... 9 
1.3 Protocol Synopsis ............................................................................................ 10 
1.4 Trial Schedule .................................................................................................. 17 
1.5 Responsibilities ................................................................................................ 21 
2 
Background Information and Scientific Rationale ..................................... 23 
2.1 Introduction to SARS-CoV-2 Virus .............................................................. 23 
2.2 ABNCoV2 Vaccine .......................................................................................... 23 
2.3 Summary of Nonclinical Studies with ABNCoV2 Vaccine ......................... 25 
2.4 Clinical Trial Data with ABNCoV2 Vaccine ................................................ 25 
2.5 Rationale .......................................................................................................... 26 
2.6 Trial Population .............................................................................................. 26 
2.7 Risk/Benefit Assessment ................................................................................. 26 
2.8 Potential Risk ................................................................................................... 26 
2.9 Benefit .............................................................................................................. 27 
3 
Objectives ........................................................................................................ 27 
4 
Trial Design ..................................................................................................... 27 
4.1 Experimental Design ....................................................................................... 27 
4.2 Description of Trial Procedures ..................................................................... 28 
4.3 Screening Visit ................................................................................................. 28 
4.4 Active Trial Phase ........................................................................................... 29 

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4.5 Follow-Up Phase .............................................................................................. 29 
4.6 Unscheduled Visit ............................................................................................ 30 
4.7 Early Discontinuation ..................................................................................... 30 
4.8 Trial Duration ................................................................................................. 31 
4.9 Data Monitoring Committee .......................................................................... 31 
4.10 Trial Halting Rules .......................................................................................... 31 
5 
Selection of Subjects ....................................................................................... 32 
5.1 Recruitment Procedure .................................................................................. 32 
5.2 Inclusion Criteria ............................................................................................ 32 
5.3 Exclusion Criteria ........................................................................................... 32 
6 
Investigational Medicinal Product ................................................................ 32 
6.1 Production, Packaging and Labeling ............................................................ 32 
6.2 Shipment, Storage and Handling ................................................................... 33 
6.3 Preparation, Administration and Dosage ..................................................... 33 
6.4 Accountability and Disposal ........................................................................... 33 
7 
Assessment of Immunogenicity ..................................................................... 34 
7.1 Humoral Immune Response ........................................................................... 34 
7.2 Cellular Immune Response ............................................................................ 34 
7.3 Future Use of Lab Specimen .......................................................................... 35 
8 
Safety and Reactogenicity .............................................................................. 35 
8.1 Definitions ........................................................................................................ 35 
8.2 Medical History ............................................................................................... 35 
8.3 Adverse Events ................................................................................................ 35 
8.4 Unsolicited AEs................................................................................................ 35 
8.5 Solicited AEs .................................................................................................... 36 
8.6 SAEs and AESIs .............................................................................................. 36 

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8.7 Relevant Medical History ............................................................................... 37 
8.8 Prior and Concomitant Medication ............................................................... 38 
8.9 Prohibited Medications ................................................................................... 38 
8.10 Physical Examination ..................................................................................... 39 
8.11 Vital Signs ........................................................................................................ 39 
8.12 Unsolicited AEs ............................................................................................... 39 
8.13 Solicited AEs .................................................................................................... 41 
8.14 Solicited Local AEs ......................................................................................... 42 
8.15 Solicited General AEs ..................................................................................... 43 
8.16 Safety Laboratory Measurements ................................................................. 43 
8.17 Cardiac Assessment ........................................................................................ 45 
8.18 Pregnancy ........................................................................................................ 45 
8.19 Reporting ......................................................................................................... 45 
8.20 Reporting of SAE and AESI........................................................................... 45 
8.21 Reporting of Pregnancies ............................................................................... 48 
9 
Statistical Considerations ............................................................................... 48 
9.1 Randomization Procedure .............................................................................. 48 
9.2 Sample Size Calculation ................................................................................. 48 
9.3 Multiplicity ...................................................................................................... 49 
9.4 Variables .......................................................................................................... 49 
9.5 Analysis Population ......................................................................................... 49 
9.6 Analysis Methods ............................................................................................ 50 
9.7 Primary Estimand ........................................................................................... 50 
9.8 Population Level Summary ............................................................................ 50 
9.9 Intercurrent Events ........................................................................................ 50 
9.10 Primary Analysis ............................................................................................. 50 

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9.11 Sensitivity and Supportive Analyses.............................................................. 51 
9.12 Secondary Estimands ...................................................................................... 51 
9.13 Population Level Summary ............................................................................ 51 
9.14 Intercurrent Events ........................................................................................ 51 
9.15 Main Analyses ................................................................................................. 52 
9.16 Sensitivity and Supportive Analyses.............................................................. 52 
9.17 Exploratory Endpoints ................................................................................... 52 
9.18 Analyses of Safety............................................................................................ 53 
9.19 Timing of Analyses .......................................................................................... 53 
9.20 Primary Analysis ............................................................................................. 53 
9.21 Final Trial Analysis ......................................................................................... 53 
10 Ethical Aspects ................................................................................................ 54 
10.1 Ethical and Legal Regulations ....................................................................... 54 
10.2 Approval by IEC/IRB ..................................................................................... 54 
10.3 Confidentiality and Data Protection .............................................................. 54 
11 Informed Consent ........................................................................................... 55 
12 Electronic Case Report Forms and Retention of Records .......................... 55 
12.1 Electronic Case Report Forms ....................................................................... 55 
12.2 Retention of Records ....................................................................................... 56 
13 Monitoring of the Trial .................................................................................. 56 
13.1 Protocol Deviations ......................................................................................... 57 
14 Audits and Inspections ................................................................................... 57 
15 Responsibility of the Investigator .................................................................. 58 
16 References........................................................................................................ 60 
17 Appendices ...................................................................................................... 62 
Appendix 1: Toxicity Scale for Laboratory Values ............................................. 62 

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Appendix 2: Grading Scale for Lymphadenopathy ............................................ 63 
Appendix 3: Interpretation Support for Assessment of Screening ECGs ......... 64 
Appendix 4: Signature Page .................................................................................. 65 
Appendix 5: Summary of Changes for Amendment#1 to the Clinical Trial 
Protocol ............................................................................................................ 68 
Appendix 6: Summary of Changes for Amendment #2 to the Clinical 
Trial Protocol .................................................................................................. 73 
 
 
List of Tables 
Table 1 
Treatment Groups and Number of Subjects ....................................................... 13 
Table 2 
Grading of Local Symptoms from the Subject’s Memory Aid .......................... 42 
Table 3 
Grading of General Symptoms from the Subject’s Memory Aid ...................... 43 
Table 4 
Description .............................................................................................................. 68 
Table 5 
Description .............................................................................................................. 73 
List of Figures 
Figure 1 
Structural Elements of ABNCoV2: 
 
 ........................................................................................................... 24 
Figure 2 
Algorithm for Reporting of SAEs and AESIs ...................................................... 47 

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1 General Information 
1.1 Abbreviation 
 
 
 
ADR 
adverse drug reaction 
AE 
adverse event 
ALT 
alanine amino transferase 
AP 
alkaline phosphokinase 
ACE2 
angiotensin-converting enzyme 2 
AESI 
adverse event of special interest 
AST 
aspartate aminotransferase 
BN 
Bavarian Nordic 
ȕ-HCG 
beta-human chorionic gonadotropin 
BMI 
body mass index 
COVID-19 
coronavirus disease 2019 
 
 
CRA 
clinical research associate 
 
 
CRO 
contract research organization 
 
 
CTS 
clinical trial site 
cVLP 
capsid virus-like particle 
DMC 
data monitoring committee 
DS 
drug safety 
ECG 
electrocardiogram 
eCRF(s) 
electronic case report form(s) 
EDC 
electronic data capture 
EAP 
end of active trial phase 
ELISPOT 
enzyme-linked immuno spot technique 
ELISA 
enzyme-linked immunosorbent assay 
EU 
European Union 
EudraCT 
European Clinical Trials Database 
FU 
follow-up 
FDA 
food and drug administration 
GCP 
good clinical practice 
HBsAG 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIV 
human immunodeficiency virus 
IB 
Investigator’s Brochure 
IEC 
independent ethics committee 
ICF 
informed consent form 
IRB 
Institutional Review Board 

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ICH 
International Conference on Harmonization 
IM 
intramuscular 
IMP 
investigational medicinal product 
MedDRA 
Medical Dictionary for Regulatory Activities 
MP 
medicinal product 
NHP 
nonhuman primate 
n/N 
number 
PBMC 
peripheral blood mononuclear cells 
PBS 
Phosphate buffered saline 
PCR 
polymerase chain reaction 
PV 
pharmacovigilance 
PI 
principal investigator 
QTc 
QT interval corrected 
RBD 
receptor binding domain 
SCR 
screening visit 
SADR 
serious adverse drug reaction 
SAE 
serious adverse event 
SARS-CoV-2 
severe acute respiratory syndrome coronavirus 2 
SOP 
standard operating procedure 
V 
visit 
WBC 
white blood cells 
WOCBP 
women of childbearing potential 

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1.2 Definitions 
 
active trial phase 
The period from the first vaccination up to and including 1 month (28- 
35 days) after receiving the last trial vaccination. For Group 1 this includes 
V1-V7. For Groups 2 and 3, this includes V1-V4. 
completed 
vaccination 
regimen 
Completed vaccination regimen with an authorized SARS-CoV-2 vaccine. 
“Authorized” SARS-CoV2 vaccine refers to authorization status at SCR, 
i.e., subjects can be eligible if they previously received investigational 
vaccines that have since been authorized for emergency use or granted full 
market licensure. “Completed” includes full primary vaccination as 
described in the labeling of the initial vaccine, but also includes any 
mix/match series of 2 doses of any authorized COVID-19 vaccine, or a 
single dose of any authorized COVID-19 vaccine in subjects who 
previously had a confirmed COVID-19 infection. 
end of active 
trial phase (EAP) 
The visit at the end of active trial phase, approximately 28 to 35 days after 
the last vaccination. In the event of early withdrawal of a subject from the 
trial during the active trial period, the EAP visit will be the visit at which 
they collect the final safety endpoints for the trial. 
last vaccination 
For Group 1 (seronegative) the last vaccination is the second vaccination of 
their two-dose prime-boost regimen, scheduled to be received at V4. For 
Groups 2 and 3 (seropositive) the last vaccination is the single boost 
vaccination received at V1. 
licensed SARS- 
CoV-2 vaccine 
licensed SARS-CoV-2 vaccine refers to the license status at the time a 
subject is screened for the trial. A subject who received a SARS-CoV-2 
vaccine during a clinical trial which has since been approved is eligible for 
the trial as the vaccine is presently considered licensed. 

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1.3 Protocol Synopsis 
 
Title 
An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and 
Immunogenicity of the ABNCoV2 Vaccine in SARS-CoV-2 
Seronegative and Seropositive Adult Subjects 
Protocol Number 
ABNCoV2-01 
Clinical Phase 
Phase 2 
Sponsor 
Bavarian Nordic A/S 
Philip Heymans Alle 3 
2900 Hellerup 
Denmark 
Trial Identifier 
EudraCT # 2021-001393-31 
Number of Sites and 
Countries 
2 sites, Germany 
Vaccination Dose 
and Schedule 
Each subject will receive either 2 doses of 100 μg (Group 1), 1 dose of 
100 μg (Group 2) or 1 dose of 50 μg (Group 3) ABNCoV2 vaccine. In 
the case of the two-dose regimen, vaccines are administered 4 weeks 
apart. 
Route of 
Administration 
ABNCoV2 vaccine is administered intramuscularly (IM) into the 
deltoid muscle of the upper arm (preferably the non-dominant arm). 
Trial Duration 
Approximately 17 weeks for initially seronegative subjects receiving 
the two-dose vaccination regimen (Group 1). 
 
Up to 104 weeks for initially seropositive subjects receiving 1 
vaccination (Group 2 and Group 3). 
Sample Size 
A total of 210 healthy adult subjects will be enrolled into 3 groups: 
x 
Approx. 30 subjects determined to be seronegative for SARS- 
CoV-2 antibodies at screening (SCR) will be enrolled in Group 1. 
x 
Approx. 90 subjects determined to be seropositive for SARS-CoV- 
2 antibodies at SCR will be enrolled in Group 2 (100 μg). 
x 
Approx. 90 subjects determined to be seropositive for SARS-CoV- 
2 antibodies at SCR will be enrolled in Group 3 (50 μg). 

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Primary Objectives 
To assess SARS-CoV-2 specific humoral immune responses of the 
ABNCoV2 vaccine in initially SARS-CoV-2 seronegative and 
seropositive subjects. 
Secondary 
Objectives 
To assess the safety and tolerability of the ABNCoV2 vaccine in adult 
seropositive and seronegative subjects. 
Exploratory 
Objectives 
To assess SARS-CoV-2 specific peak humoral immune responses after 
the prime-boost regimen (Group 1) or the booster dose (Group 2 and 
Group 3) of the ABNCoV2 vaccine. 
 
To explore SARS-CoV-2 specific cellular immune responses to the 
ABNCoV2 vaccine. 
 
To assess SARS-CoV-2 specific neutralizing immune responses 
against variant strains circulating at the time of analysis. 
Primary Endpoints 
SARS-CoV-2 neutralizing antibody titers at 2 weeks after the last 
vaccination, i.e., after the second vaccination in initially seronegative 
subjects and after the single boost vaccination in initially seropositive 
subjects. 
Secondary Endpoints 
Subjects reporting any SAEs or AESIs assessed as related to trial 
vaccine within 8 days after vaccination. 
 
Subjects reporting any Grade 3 or higher AEs assessed as related to 
trial vaccine within 8 days after vaccination. 
Exploratory 
Endpoints 
Group 1 (seronegative subjects): 
SARS-CoV-2 neutralizing antibody titers at 2 and 4 weeks post-prime 
vaccination and 1, 4, and 13 weeks post-boost vaccination. 
SARS-CoV-2 total antibody titers at all serum sampling time points. 
Groups 2 and 3 (seropositive subjects): 
SARS-CoV-2 neutralizing antibody titers at 1 week, 4 weeks, 
3 months, 6 months, 1 year and 2 years after vaccination. 
 
SARS-CoV-2 total antibody titers at all serum sampling timepoints. 

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Groups 1, 2 and 3 (all subjects): 
Cellular immune response, e.g., by Interferon-J / Interleukin-4 
ELISPOT, at 1 week after the last vaccination, i.e., after the second 
vaccination in initially seronegative subjects and after the single boost 
vaccination in initially seropositive subjects. 
SARS-CoV-2 neutralizing antibody titers against variant strains 
circulating at the time of analysis at 2 weeks after last vaccination. 
Safety Endpoints 
Subjects reporting any SAE or AESI, regardless of relationship, within 
29 days after vaccination. 
 
Subjects reporting any Grade 3 or higher AEs assessed as related to 
trial vaccine within 29 days after vaccination. 
 
Subjects reporting solicited local AEs within 8 days after vaccination. 
 
Subjects reporting solicited general AEs within 8 days after 
vaccination. 
Trial Design 
A prior phase 1, dose ranging trial in healthy, seronegative adults 
evaluates safety and reactogenicity with doses up to 70μg, “First-in- 
human Trial of the Coronavirus Virus-like Particle Subunit Vaccine 
ABNCoV2 in SARS-CoV-2-naïve Adult Volunteers in Good Health” 
(COUGH-1; EudraCT no. 2020-004621-22, NCT04839146). 
 
For this Phase 2 trial ABNCoV2-01, in a run in phase 6 adults 
(comprising of 3 subjects in each Group 1 and 2) will be vaccinated at 
1 clinical trial site in a consecutive manner, with an at least 48 hours 
interval between the first and second subject of each group, then the 
second and third subject dosed on consecutive days, before opening up 
to full enrollment of the trial. Safety assessments will be based on 
solicited and unsolicited AE data (first week after first vaccination) 
evaluated by an independent Data Monitoring Committee (DMC). 
After a positive DMC recommendation, enrollment to the rest of 
Groups 1 and 2 of the trial will commence. Group 3 subjects will be 
enrolled after completion of Group 2 enrollment. 
This phase 2 trial will evaluate a homologous prime-boost regimen 
with 100 μg ABNCoV2 in initially seronegative adult subjects 
(Group 1), as determined by a qualitative test for SARS-CoV-2 
antibodies, compared to a single boost vaccination of 100 μg (Group 

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2) or 50 μg (Group 3) of ABNCoV2 in initially seropositive subjects, 
as defined by a positive qualitative test for SARS-CoV-2 antibodies 
and either a history of SARS-CoV-2 vaccination or previous COVID- 
19 disease at least 90 days prior to enrollment (Table 1). 
Table 1 
Treatment Groups and Number of Subjects 
 
 
 
 
 
 
 
 
N = number of subjects 
a n = 3 of Group 1 and Group 2 (total 6 subjects) will be enrolled in the run-in 
phase before opening the trial to full enrollment. 
 
For the seropositive subjects (Groups 2 and 3), the reason for 
seropositivity will be documented (e.g., previous COVID-19 disease, 
previous mRNA-based vaccination regimen, or previous Adenovirus- 
based vaccination regimen). 
 
Due to the timing of the addition of Group 3, enrollment into Group 2 
will be completed prior to enrolling subjects into Group 3. Therefore, 
no randomization will be required for the seropositive subjects. 
Trial Halting Criteria 
A temporary halting or termination of the trial as a whole can be 
decided in case of: 
x 
an SAE or serious AESI with an at least reasonable possibility 
of a causal relationship to the administration of ABNCoV2 
vaccine 
x 
an unexpected Grade 3 or higher systemic reaction or lab 
toxicity with at least a reasonable possibility of a causal 
relationship to the administration of ABNCoV2 vaccine 
These parameters are not all-inclusive. Other AEs could occur that 
would trigger a DMC review. Any member of the DMC, the PI and/or 
the BN Medical Monitor could request a DMC review based on any 
observation. 
Dose 
(/0.3 mL) 
Treatment Groups 
Total 
N 
Seronegative 
Seropositive 
100 μg 
Group 1 
30 subjectsa 
Group 2 
90 subjectsa 
120 
50 μg 
 
Group 3 
90 subjects 
90 
Total 
210 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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If an event fulfilling the trial halting criteria reaches the investigator’s 
attention, the investigator has the responsibility to alert the Clinical 
Safety and Pharmacovigilance Department and Medical Monitor 
within 24 hours and provide comprehensive documentation of the 
event. 
Inclusion Criteria 
1. Subjects \HDUV of age at SCR. 
2. Seronegative (Group 1): negative qualitative test for SARS- 
CoV-2 antibodies at SCR. 
Seropositive (Group 2 and Group 3): Previous COVID-19 
disease or previously completed vaccination regimen with an 
authorized SARS-CoV-2 vaccine at least 90 days before 
planned trial vaccination, and a positive qualitative test for 
SARS-CoV-2 antibodies at SCR. “Authorized” SARS-CoV-2 
vaccine refers to authorization status at SCR, i.e., subjects can 
be eligible if they previously received investigational vaccines 
that have since been authorized for emergency use or granted 
full market licensure. Receipt of a single dose of an authorized 
COVID-19 vaccine regimen in subjects with a previous 
diagnosis of COVID-19 or a mix/match series of 2 doses of any 
authorized COVID-19 vaccine will be considered as a 
completed vaccination. 
3. General good health, without acute medical illness, physical 
exam findings, or laboratory abnormalities, as determined by 
the investigator. 
4. Prior to performance of any trial specific procedures, the 
subject has read, signed and dated an informed consent form 
(ICF), having been advised of the risks and benefits of the trial 
in a language understood by the subject. 
5. Body mass index %0, and <40. 
6. Female subjects of childbearing potential (WOCBP) must 
agree to the use of an effective method of birth control from at 
least 30 days prior to administration of the vaccine until 
30 days after the vaccination. Male subjects who are sexually 
active with a WOCBP must agree to the use of an effective 
method of birth control from the day of administration of the 
vaccine until 30 days after the vaccination. A woman is 
considered of childbearing potential unless post-menopausal 
(defined as  months without a menstrual period at SCR) or 
surgically sterilized (bilateral oophorectomy, bilateral tubal 
ligation, hysterectomy). Acceptable contraception methods are 

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restricted to abstinence (abstinence only acceptable if 
refraining from heterosexual intercourse during the entire 
period of 30 days prior to administration of the vaccine until 30 
days after the vaccination), double barrier contraceptives, 
vasectomy, intrauterine contraceptive devices or licensed 
hormonal products. 
7. WOCBP must have a negative serum pregnancy test at SCR. 
8. Negative human immunodeficiency virus antibody test 
(anti-HIV), negative hepatitis B surface antigen (HBsAG) and 
negative antibody to hepatitis C virus (HCV). 
Exclusion Criteria 
1. Group 1 only: History of COVID-19 infection or previous 
vaccination with a licensed or candidate SARS-CoV-2 vaccine, 
or positive qualitative test for SARS-CoV-2 antibodies at SCR. 
Groups 2 and 3 only: History of COVID-19 infection and 
subsequent receipt of more than one licensed or candidate 
SARS-CoV-2 vaccine. 
2. Positive test for SARS-CoV-2 infection at SCR. 
3. Pregnant or breastfeeding women. 
4. Subject has an acute or chronic medical condition that, in the 
opinion of the investigator, would render the trial procedures 
unsafe or would interfere with the evaluation of the responses. 
5. History of or active autoimmune disease. History of Guillain- 
Barré syndrome or Reye’s syndrome. Persons with vitiligo or 
thyroid disease taking thyroid replacement are not excluded. 
6. Known or suspected impairment of immunologic functions 
including, but not limited to, known immunodeficiency 
syndrome. 
7. History of malignancy other than squamous cell or basal cell 
skin cancer, unless there has been surgical excision at least 
6 months prior to SCR that is considered to have achieved cure. 
Subjects with history of skin cancer must not be vaccinated at 
the previous tumor site. 
8. Laboratory parameters (such as complete blood count, serum 
biochemistry including aspartate aminotransferase [AST], 
alanine amino transferase [ALT], alkaline phosphokinase [AP], 
bilirubin, or creatinine values), pulse rate, blood pressure, or 
electrocardiogram (ECG) outside normal range at SCR and 
deemed clinically relevant by the investigator. 
9. Clinically significant mental disorder not adequately controlled 
by medical treatment. 

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10. Active or recent history (within 6 months before SCR) of 
chronic alcohol abuse, intravenous drug abuse, or nasal drug 
abuse. 
11. History of allergic disease or reactions likely to be exacerbated 
by any component of the vaccine. 
12. History of anaphylaxis or severe allergic reaction to any 
vaccine. 
13. Having received any vaccinations or planned vaccinations with 
a live vaccine within 30 days prior to or after trial vaccination. 
14. Having received any vaccinations or planned vaccinations with 
an inactivated vaccine within 14 days prior to or after trial 
vaccination. 
15. Recent blood donation (including platelets, plasma and red 
blood cells) within 4 weeks prior to SCR, or planned blood 
donations during the active trial phase. 
16. Chronic systemic administration (defined as more than 14 days 
of >5 mg prednisone [or equivalent]/day), or any other 
immune-modifying drugs during a period starting 3 months 
prior to administration of the vaccine and ending 4 weeks after 
the last vaccination. The use of topical, inhaled, ophthalmic and 
nasal glucocorticoids is allowed. 
17. Post organ transplant subjects, whether or not receiving chronic 
immunosuppressive therapy. 
18. Administration or planned administration of immunoglobulins 
and/or any blood products during a period starting 3 months 
prior to administration of the vaccine and ending 4 weeks after 
the last vaccination. Receipt of packed red blood cells given for 
an emergency indication in an otherwise healthy person, and 
not required as ongoing treatment is not exclusionary (for 
example packed red blood cells given in emergency during an 
elective surgery). 
19. Use of any investigational or non-registered drug or vaccine 
other than the trial vaccine within 30 days preceding the 
administration of trial vaccine, or planned administration of 
such a drug or vaccine throughout the trial. 
20. Clinical trial site personnel involved in this trial. 

 
 
 
 
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1.4 Trial Schedule 
Group 1 Two-dose Vaccination Schedule (Seronegative Subjects): 
 
Visit (V) 
SCR 
V1 
V2 
V3 
V4 
V5 
V6 
V7/EAP 
FU1 
Day / Visit +… Days 
-14--1 
1 
V1 
+5-7 
V1 
+12-16 
V1 
+28-35 
V4 
+7-10 
V4 
+12-16 
V4 
+28-35 
V4 
+91-105 
Target week 
-2 
0 
1 
2 
4 
5 
6 
8 
17 
Informed consent 
X 
 
 
 
 
 
 
 
 
Check incl./excl. criteria 
X 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Complete physical exama 
(body height and weight, BMI assessment) 
X 
 
 
 
 
 
 
 
 
Evaluation of vital signsa 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Targeted physical exam incl. auscultation 
of the heart and lunga 
 
X 
X 
X 
X 
X 
X 
X 
X 
ECGa 
X 
 
 
 
 
 
 
 
 
Recording of prior and concomitant 
medication 
X 
X 
X 
X 
X 
X 
X 
X 
 
Counseling on avoidance of pregnancy for 
WOCBPb 
X 
X 
 
 
X 
 
 
 
 
AE/SAE/AESI recording 
Xi 
X 
X 
X 
X 
X 
X 
X 
Xc 
Pregnancy test for WOCBPd 
X 
X 
 
 
X 
 
 
X 
 
Obtaining blood for safety laba 
X 
 
 
X 
 
 
X 
Xe 
 
SARS-CoV-2 specific antibody test 
X 
 
 
 
 
 
 
 
 
SARS-CoV-2 infection test (PCR) 
X 
 
(X) 
(X)f 
(X)f 
(X)f 
(X)f 
(X)f 
(X)f 
Hep-B, HCV, HIV test 
X 
 
 
 
 
 
 
 
 

 
 
 
 
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Visit (V) 
SCR 
V1 
V2 
V3 
V4 
V5 
V6 
V7/EAP 
FU1 
Day / Visit +… Days 
-14--1 
1 
V1 
+5-7 
V1 
+12-16 
V1 
+28-35 
V4 
+7-10 
V4 
+12-16 
V4 
+28-35 
V4 
+91-105 
Target week 
-2 
0 
1 
2 
4 
5 
6 
8 
17 
Serum collection for antibody testingg 
 
X 
 
X 
X 
X 
X 
X 
X 
Collection of PBMCg 
 
X 
 
 
 
X 
 
 
 
Vaccine administration 
& subject observation  minutes) 
 
X 
 
 
X 
 
 
 
 
Recording of immediate AEs 
 
X 
 
 
X 
 
 
 
 
Handout of memory aid 
 
X 
 
 
X 
 
 
 
 
Collection of memory aid h 
 
 
X 
 
 
X 
 
 
 
Examination of injection site 
 
 
X 
 
 
X 
 
 
 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; BMI = body mass index; EAP = end of active phase visit; ECG = 
electrocardiogram; FU = follow-up; Hep-B = hepatitis-B; HCV = hepatitis-C virus; HIV = human immune deficiency virus; PBMC = 
peripheral blood mononuclear cells; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SCR = 
Screening; WOCBP = woman of childbearing potential; 
X: mandatory; (X): if indicated/if applicable 
a If clinically indicated, additional safety measures can be taken at any other trial visits or at unscheduled visits. In addition, auscultation of the 
heart and lungs will be performed to check specifically for signs of any heart condition or respiratory disorders 
b Review of acceptable contraceptive methods and recent menstrual history with WOCBP 
c Only SAEs/AESIs will be collected during the follow-up period (FU1) 
d At SCR, a serum test must be performed. At other visits, a urine pregnancy test will be performed 
e Only for subjects who discontinued during the trial and coming for EAP visit to obtain final safety data (Section 4.7) 
f At any time during the trial starting 2 weeks after vaccination if clinically indicated, e.g. in the presence of COVID-19 typical symptoms 
g Any serum blood or PBMC samples must be taken before vaccination 
h If symptoms persist at Day 8, daily symptoms and temperature will continue to be measured and documented each day until resolved 
i AESIs are not collected until vaccine has been received at visit 1. 

 
 
 
 
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Group 2 and Group 3 One-dose Vaccination Schedule (Seropositive Subjects): 
 
Visit (V) 
SCR 
V1 
V2 
V3 
V4/EAP 
FU1 
FU2 
FU3 
FU4 
Day / Visit +… Days 
-14--1 
1 
V1 
+7-10 
V1 
+12-16 
V1 
+28-35 
V1 
+91-105 
V1 
+181-195 
V1 
+361-375 
V1 
+722-736 
Target week 
-2 
0 
1 
2 
4 
13 
26 
52 
104 
Informed consent 
X 
 
 
 
 
 
 
 
 
Check incl./excl. criteria 
X 
X 
 
 
 
 
 
 
 
Medical History 
X 
 
 
 
 
 
 
 
 
Complete physical exama 
(body height and weight, BMI 
assessment) 
X 
 
 
 
 
 
 
 
 
Evaluation of vital signsa 
X 
X 
X 
X 
X 
X 
 
 
 
Targeted physical exam incl. 
auscultation of the heart and lunga 
 
X 
X 
X 
X 
X 
 
 
 
ECGa 
X 
 
 
 
 
 
 
 
 
Recording of prior and concomitant 
medication 
X 
X 
X 
X 
X 
X 
 
 
 
Counseling on avoidance of 
pregnancy for WOCBPb 
X 
X 
 
 
 
 
 
 
 
AE/SAE/AESI recording 
Xi 
X 
X 
X 
X 
Xc 
Xc 
Xc 
Xc 
Pregnancy test for WOCBPd 
X 
X 
 
 
X 
 
 
 
 
Obtaining blood for safety laba 
X 
 
 
X 
Xe 
 
 
 
 
SARS-CoV-2 specific antibody test 
X 
 
 
 
 
 
 
 
 
SARS-CoV-2 infection test (PCR) 
X 
 
(X) 
(X)f 
(X)f 
(X)f 
(X)f 
(X)f 
(X)f 
Hep-B, HCV, HIV test 
X 
 
 
 
 
 
 
 
 

 
 
 
 
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Visit (V) 
SCR 
V1 
V2 
V3 
V4/EAP 
FU1 
FU2 
FU3 
FU4 
Day / Visit +… Days 
-14--1 
1 
V1 
+7-10 
V1 
+12-16 
V1 
+28-35 
V1 
+91-105 
V1 
+181-195 
V1 
+361-375 
V1 
+722-736 
Target week 
-2 
0 
1 
2 
4 
13 
26 
52 
104 
Serum collection for antibody 
testingg 
 
X 
X 
X 
X 
X 
X 
X 
X 
Collection of PBMCg 
 
X 
X 
 
 
 
 
 
 
Vaccine administration 
& subject observation  minutes) 
 
X 
 
 
 
 
 
 
 
Recording of immediate AEs 
 
X 
 
 
 
 
 
 
 
Handout of memory aid 
 
X 
 
 
 
 
 
 
 
Collection of memory aid h 
 
 
X 
 
 
 
 
 
 
Examination of injection site 
 
 
X 
 
 
 
 
 
 
Abbreviations: AE = adverse event; AESI = adverse event of special interest; BMI = body mass index; EAP = end of active phase visit; ECG = 
electrocardiogram; FU = follow-up; Hep-B = hepatitis-B, HCV = hepatitis C virus; HIV = human immune deficiency virus; PBMC = 
peripheral blood mononuclear cells; SAE = serious adverse event; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SCR = 
Screening; WOCBP = woman of childbearing potential. 
X: mandatory; (X): if indicated/if applicable 
a If clinically indicated, additional safety measures can be taken at any other trial visits or at unscheduled visits In addition, auscultation of the 
heart and lungs will be performed to check specifically for signs of any heart condition or respiratory disorders 
b Review of acceptable contraceptive methods and recent menstrual history with WOCBP 
c Only SAEs/AESIs will be collected during the follow-up period (FU1-FU4) 
d At SCR, a serum test must be performed. At other visits, a urine pregnancy test will be performed 
e Only for subjects who discontinued during the trial and coming for EAP visit to obtain final safety data (Section 4.7) 
f At any time during the trial starting 2 weeks after vaccination if clinically indicated, e.g. in the presence of COVID-19 typical symptoms 
g Any serum blood or PBMC samples must be taken before vaccination 
h If symptoms persist at Day 8, daily symptoms and temperature will continue to be measured and documented each day until resolved 
i AESIs are not collected until vaccine has been received at visit 1. 

 
 
 
 
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1.5 Responsibilities 
 
Trial Number 
ABNCoV2-01 
Title 
An Open Label Phase 2 Trial to Evaluate the 
Safety, Tolerability and Immunogenicity of the 
ABNCoV2 Vaccine in SARS-CoV-2 Seronegative 
and Seropositive Adult Subjects 
EudraCT # 2021-001393-31 
Sponsor 
Bavarian Nordic A/S 
Philip Heymans Alle 3 
2900 Hellerup 
Denmark 
Phone (direct office) 
 
E-mail 
info@bavarian-nordic.com 
Project Leader 
 
 
 
 
Phone 
 
E-mail 
 
Medical Monitor 
 
 
 
 
 
Phone 
 
E-mail 
 
Trial Statistician 
 
 
 
 
Phone 
 
E-mail 
 
CRO Project Manager 
 
 
 

 
 
 
 
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Phone 
 
E-mail 
 
Laboratory 
(Immunogenicity 
testing) 
 
 
 
 
Phone 
 
E-mail 
 

 
 
 
 
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2 Background Information and Scientific Rationale 
2.1 Introduction to SARS-CoV-2 Virus 
SARS-CoV-2 infection, which causes coronavirus disease 2019 (COVID-19), is an ongoing 
worldwide public health emergency. The SARS-CoV-2 virus is not only highly infectious, but 
infections may lead to humoral immune responses with low virus neutralizing capacity (Chen et 
al., 2020, Robbiani et al., 2020, Wu et al., 2020). 
SARS-CoV-2 entry into cells occurs through interaction of the virus spike receptor binding 
domain (RBD) with the angiotensin-converting enzyme 2 (ACE2) protein on human cells. Upon 
binding, ACE2 acts as a receptor and human proteases are recruited to mediate cell entry (Shang 
et al., 2020a). 
In convalescent COVID-19 patients, despite generally low humoral responses, neutralizing 
antibodies specific to the RBD of SARS-CoV-2 are recurrently found (Robbianiet al., 2020). 
Interestingly, SARS-CoV-2 may be more effective in evading an effective immune response than 
SARS-CoV-2 (the coronavirus that causes SARS) because the SARS-CoV-2 spike more 
frequently assumes a conformational state that hides the spike RBD (Shang et al., 2020b, Walls et 
al., 2020, Wrapp et al., 2020). Therefore, displaying the spike RBD of SARS-CoV-2 in a manner 
that facilitates recognition by the immune system is likely to be protective against COVID-19. 
2.2 ABNCoV2 Vaccine 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
 
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2.3 Summary of Nonclinical Studies with ABNCoV2 Vaccine 
The immunogenicity of ABNCoV2 has been demonstrated in mice (Fougeroux et al., 2021) and 
in non-human primates (NHP). A single intramuscular (IM) administration of 100 μgABNCoV2 
induced SARS-CoV-2 neutralizing antibodies in NHP at comparable levels as found in human 
convalescent samples, while neutralizing antibody titers induced by 15 Pg ABNCoV2 remained 
below convalescent levels. A second administration of 15 or 100 Pg ABNCoV2 led to a >50-fold 
increase in titers. While 15 Pg ABNCoV2 administered 2-times to NHP resulted in significantly 
reduced lung viral load after SARS-CoV-2 challenge compared to nonvaccinated control animals, 
the higher dose of 100 Pg ABNCoV2 administered 2-times was more effective in that the 
majority of animals were completely free of virus in lung and also in nasal swabs, demonstrating 
complete protection. Therefore, the high dose administered 2-times has been chosen to be 
evaluated in seronegative subjects in the phase 2 trial (a single high dose boost regimen will be 
administered to seropositive subjects). 
The safety and good tolerability of 100 Pg ABNCoV2 (adjuvanted in a squalene in water 
emulsion) administered 2- or 3-times in rabbits was shown in a Good Laboratory Practice (GLP) 
compliant repeat dose toxicity and local tolerance study, that did not raise any safety concerns for 
human use. 
The ABNCoV2 dose administered to rabbits translates to a human equivalent dose based on body 
surface area (FDA, 2005) of 774 Pg for a 60 kg human; this provides a safety margin of >7x 
higher than the 100 Pg human dose. Even when taking into account an offset between 
laboratories using different reagents to determine the ABNCoV2 protein concentration, a 
potentially lower dose of 70 Pg instead of 100 Pg used in the toxicity study translates to a human 
equivalent dose of 542 Pg for a 60 kg human and still provides a safety margin of >5x higher 
than the 100 Pg human dose in this phase 2 trial. Further, the number of vaccine applications (3) 
was in excess of the 1-2 administrations planned in this phase 2 trial, thereby providing an 
additional safety margin. 
See further details in the current effective ABNCoV2 IB. 
2.4 Clinical Trial Data with ABNCoV2 Vaccine 
To date, no clinical trials with ABNCoV2 vaccine have been completed. A first in human trial is 
currently ongoing (COUGH-1, EudraCT no. 2020-004621-22/ NCT04839146), and has recruited 
first subjects in mid-March 2021. In a predefined dose escalation, SARS-CoV-2 naïve subjects 
will receive up to 70 μg of the ABNCoV2 vaccine in this phase 1 trial. Preliminary safety results 
in 45 subjects dosed up to 70 μg did not show any relevant safety findings. No final results from 
this trial are available yet. For further dose justification, please refer to Section 2.3. 

 
 
 
 
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2.5 Rationale 
SARS-CoV-2 infection, which causes COVID-19, is an ongoing worldwide public health 
emergency. The SARS-CoV-2 virus is not only highly infectious, but infections may lead to 
humoral immune responses with low virus neutralizing capacity (Chen et al., 2020, Robbianiet 
al., 2020, Wu et al., 2020). 
Despite the recent approval of several SARS-CoV-2 vaccines using different technologies, such 
as mRNA-based or adenovirus-vectored vaccines, there is still substantial spread of COVID-19 
disease and related disease burdens. These burdens include fatal outcomes as well as the need for 
continued lockdown or social distancing measures, causing a high economic and societal impact. 
The recent emergence of variant strains with yet unknown susceptibility to the currently available 
vaccines highlights the potential need for continuous adaptation of vaccines and the necessity to 
administer re-vaccinations (boosts) in populations considered at relevant risk. 
Based on the assumption that large parts of the population will obtain at least an initial 
SARS-CoV-2 vaccination regimen in the coming months, potential medical need is expected to 
be related to the availability of boost vaccinations for seropositive subjects in order to maintain or 
adapt immunogenicity to continuously circulating strains of SARS-CoV-2. 
This trial will, therefore, evaluate an initial two-dose vaccination regimen of ABNCoV2 in 
seronegative subjects as well as single dose boost regimens at two different strengths (50 ug and 
100 ug/dose) of ABNCoV2 in seropositive subjects. This will provide meaningful insights into 
the safety, tolerability and immunogenicity of both vaccination regimens, and will confirm 
whether a single dose boost regimen in seropositive subjects will elicit a comparably high 
immune response as expected for the two-dose regimen based on the available nonclinical data. 
2.6 Trial Population 
Women and men of any ethnicity DJHG\HDUVZKR meet all the inclusion and none of the 
exclusion criteria are eligible for enrollment into this trial. 
2.7 Risk/Benefit Assessment 
2.8 Potential Risk 
Blood drawing may cause discomfort, bruising, light-headedness or fainting. Rarely, a blood 
draw may result in infection at the site of venipuncture. 
Based on the available data obtained in the nonclinical rabbit toxicology study, the dose levels 
planned for this phase 2 trial are not expected to cause any major risks. 

 
 
 
 
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As with all vaccines, there is a risk of an allergic reaction or an anaphylactic event. Trial site staff 
will observe subjects for at least 30 minutes after each vaccination and, in the event that a severe 
allergic reaction and/or dyspnoea might occur, appropriate medical treatment and supervision 
will be readily available. 
Based on available data from COUGH-1 study, there have been no SAEs reported. 
As with all vaccines, there is a risk of temporary mild to moderate injection site reactions, such as 
injection site pain and/or tenderness, erythema, swelling, pruritus or induration. The above 
mentioned were reported most commonly in the COUGH-1 study following both doses of study 
vaccine. Also, systemic inflammatory reactions including flu-like symptoms such as fever, 
headache, nausea, muscle pain, chills or fatigue can occur. Headache, chills and fatigue were 
reported most commonly in the COUGH-1 study after first dose of study vaccine. After the 
second dose of study vaccine, myalgia was mostly commonly reported, followed by nausea, 
hyperhidrosis and a general feeling of warmth without fever. 
2.9 Benefit 
There will be no direct benefit to the trial subjects. Trial subjects will contribute significantly to 
the development of a vaccine targeting COVID-19 disease. Subjects might potentially acquire 
protection against SARS-CoV-2 virus. However, it cannot be said if the vaccine is efficacious 
against the COVID-19 disease in humans, as efficacy data available for the ABNCoV2 vaccine 
have so far been obtained in animal models only. Analysis of the samples collected will not 
directly benefit the subject. 
3 Objectives 
Please refer to Protocol Synopsis Section 1.3. 
4 Trial Design 
4.1 Experimental Design 
The trial is designed as an open label phase 2 trial to evaluate safety, tolerability and 
immunogenicity of the ABNCoV2 vaccine after IM application. The trial will evaluate a 
homologous prime-boost regimen with 100 μg ABNCoV2 in initially seronegative adult subjects 
(Group 1), as determined by a qualitative test for SARS-CoV-2 antibodies, compared to a single 
boost vaccination with either 100 μg or 50 μg dose of ABNCoV2 in initially seropositive subjects 
(Groups 2 and 3), as defined by a positive qualitative test for SARS-CoV-2 antibodies and a 
history of SARS-CoV-2 vaccination or previous COVID-19 disease at least 90 days prior to 
enrollment (Table 1). 

 
 
 
 
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In total, approximately 210 subjects will be enrolled in this trial. Recruitment will start with a 
run-in phase of 6 subjects (3 in each of Groups 1 and 2, respectively, at least 48 hours interval 
between the first and second subject in each group, the second and third subject dosed on 
consecutive days) before opening up enrollment to both treatment groups. Safety assessments 
will be based on solicited and unsolicited AE data evaluated by an independent Data Monitoring 
Committee (DMC) who will review the safety information collected at the Week 1 Visit (V2). 
After a positive DMC recommendation for each of the groups, enrollment of the rest of Groups 1 
and 2 of the trial will commence. 
Due to the timing of the addition of Group 3, enrollment into Group 2 will be completed prior to 
enrolling subjects into Group 3. Therefore, no randomization will be required for the 
seropositive subjects. 
4.2 Description of Trial Procedures 
The trial procedures will be conducted according to the trial procedure schedule (Section 1.4) and 
as described on the following pages. Visits must be scheduled within the protocol-allowed visit 
windows. 
4.3 Screening Visit 
All subjects must be thoroughly informed about all aspects of the trial (e.g., trial visit schedule, 
required evaluations and procedures, risks and benefits) as described in the informed consent 
form (ICF). Written informed consent must be obtained according to local requirements before 
any trial-related assessments may be carried out. 
After the ICF has been collected, subjects will enter a screening period of up to 14 days before 
the first vaccination. Screening procedures are listed in the trial procedure schedule in 
Section 1.4. 
If a subject has been screened and cannot be vaccinated because of a certain transient condition 
(e.g., abnormal lab value due to an acute condition or a missing lab evaluation due to mishandling 
of the sample), the respective test(s) should be repeated. The re-test must be performed within the 
14-day window started by the initial SCR visit. 
If a subject cannot be vaccinated due to other circumstances (e.g., completion of a wash-out 
period for a medication or vaccine not allowed during the trial) leading to a delay over the 14-day 
window, a complete re-screening must be performed and a new subject number will be assigned. 
The clock then re-starts at the new SCR visit within 14 days before first vaccination. A subject 
may be fully re-screened only once. 

 
 
 
 
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4.4 Active Trial Phase 
After successfully passing the screening evaluations, the eligible volunteers can enter the active 
trial phase starting with V1 and ending at either V4 (Group 2 and Group 3, single boost 
vaccination), V7 (Group 1, two-dose prime-boost vaccination schedule), or premature 
discontinuation. 
The procedure is described further in the Protocol Synopsis (Section 1.3). 
The procedures performed at V1 and all following visits are listed in the trial procedure schedule 
in Section 1.4. Collection of immunogenicity samples and all other examinations listed above the 
vaccination event in the trial schedule must always be performed prior to vaccine administration. 
At V1/Day 1 each subject in Groups 1 and 2 will receive 1 dose of 100 μg ABNCoV2 vaccine, 
and Group 3 will receive 1 dose of 50 μg ABNCoV2 vaccine administered IM into the deltoid 
muscle of the upper arm (preferably the non-dominant arm). For Group 1 only, at V4 a second 
dose of 100 μg ABNCoV2 vaccine will be administered IM into the deltoid muscle of the upper 
arm (preferably the non-dominant arm). 
Following the vaccination subjects will be kept under close observation at the clinical trial site 
(CTS) for at least 30 minutes, with appropriate medical treatment readily available in case of a 
rare anaphylactic reaction following vaccine administration. Any AEs occurring during or after 
vaccine administration and observation period will be recorded immediately. 
Solicited local and general AEs will be collected on a memory aid completed daily by the subject 
for an 8-day period, beginning with the day of vaccination. For each subject in Group 1, two 
memory aids will be collected (one for each of the two vaccinations). The memory aid will be 
returned to the clinic staff at the following visit. If symptoms persist at Day 8, daily symptoms 
and temperature will continue to be measured and documented each day until resolved (Section 
8.13). Unsolicited AEs will be assessed as described in Section 8.12. 
4.5 Follow-Up Phase 
To monitor long-term safety and immunogenicity, all subjects in Groups 1, 2 and 3 will come to 
the CTS for follow-up visits (FU1) 3 months after the last vaccination. 
For additional immunogenicity and safety readouts, the Group 2 and Group 3 (initially 
seropositive) subjects, will come to the CTS for FU visits at 3 months (FU1), 6 months (FU2), 1 
year (FU3) and 2 years (FU4) after their vaccination. 
The procedures performed at the FU Visits are listed in the trial procedure schedule in Section 1.4 

 
 
 
 
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4.6 Unscheduled Visit 
Clinically indicated additional visits may be necessary between scheduled visits. Unscheduled 
visits may be performed, e.g., to repeat laboratory testing or physical exams due to a new 
development. Examinations performed at unscheduled visits will be documented in the source 
documents as well as in the respective electronic case report form (eCRF) sections for 
unscheduled visits. 
4.7 Early Discontinuation 
Reasons for early discontinuations: 
A subject may be discontinued from the trial early for different reasons. The decision to 
discontinue early can be made by the investigator or by the subject. Reasons for early 
discontinuation of a subject may include, but are not limited to: 
x 
An AE/SAE/AESI that, in the opinion of the investigator, makes it unsafe for the subject to 
receive a vaccination 
x 
Pregnancy 
x 
An anaphylactic reaction following the administration of any vaccine(s) 
x 
Clinical need for concomitant or ancillary therapy not permitted in the trial as outlined in 
Section 8.8. 
x 
Subject’s receipt of an approved booster vaccination for SARS-CoV-2. 
x 
Subject’s request to discontinue (withdrawal of consent to participate). 
x 
Subject unwilling or unable to comply with trial requirements. 
x 
Any reason that, in the opinion of the investigator, requires or supports early 
discontinuation of a subject. 
Handling of early discontinuations: 
Each subject has the right to terminate their trial participation completely at any time for any 
reason, and the investigator may also terminate a subject’s trial participation. Subjects whose trial 
participation is terminated during the active trial phase should undergo a concluding EAP visit, 
including safety laboratory testing and pregnancy test for WOCBP. The subject has the right to 
refuse the optional EAP visit, however, the CTS should make an effort to collect any safety data 
possible for the subject. If the subject consents, the 3-month FU visit (FU1) should still be 
performed to collect any potential SAEs/AESIs which occurred after the last vaccination. 
Subjects who discontinued after receiving trial vaccine will not be replaced. 

 
 
 
 
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4.8 Trial Duration 
The total duration of subject participation in the trial will be up to 104 weeks (one-dose 
vaccination schedule) or 17 weeks (two-dose vaccinations schedule). The duration of the trial as a 
whole ultimately depends on the length of the recruitment period. 
4.9 Data Monitoring Committee 
The DMC is an independent board that oversees the safety of subjects participating in the trial. 
The members of the DMC are independent experts with experience in infectious diseases. The 
primary responsibility of the DMC is to review and evaluate the accumulated trial safety data and 
make recommendations to proceed to open enrollment for remaining subjects. 
If an event occurs which fulfills the trial halting rules (see Section 4.10 for further details), the 
DMC will review the event in a timely manner and agree on a recommendation to halt, resume or 
terminate the trial participation of the affected subject(s) and/or the trial as a whole. 
A separate charter will describe in detail the relevant operational procedures, communication 
pathways, roles and responsibilities of the DMC. 
4.10 Trial Halting Rules 
The Trial Halting Criteria are as follows: 
A temporary halting or termination for the trial as a whole can be decided in case of: 
x 
a SAE with an at least reasonable possibility of a causal relationship to the administration 
of ABNCoV2 vaccine 
x 
an unexpected Grade 3 or higher systemic reaction or lab toxicity with at least a reasonable 
possibility of a causal relationship to the administration of ABNCoV2 vaccine 
These parameters are not all-inclusive. Other AEs could occur that would trigger a DMC review. 
Any member of the DMC, the Principal Investigator (PI) and/or the Bavarian Nordic (BN) 
Medical Monitor or safety physician could request a DMC review based on any observation. 
If an event fulfilling the trial halting criteria reaches the investigator’s attention, the investigator 
has the responsibility to alert the Clinical Safety and Pharmacovigilance (PV) Department and 
Medical Monitors within 24 hours and provide comprehensive documentation of the event. 

 
 
 
 
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5 Selection of Subjects 
The investigators will keep a log of subjects screened for the trial and provide the reason in case 
of exclusion. Information about every screened subject will be documented in the eCRF. 
For subjects not fulfilling the eligibility criteria the minimum information documented in the 
eCRF is confirmation of the ICF signature, demographics and reason for screen failure. 
5.1 Recruitment Procedure 
Subjects will be recruited actively. Recruitment strategies will be evaluated by BN prior to 
IRB/IEC approval. Subjects identified as potential subjects in the trial will be provided with all 
the necessary information required to make an informed decision about their participation in the 
trial. 
5.2 Inclusion Criteria 
Please refer to Protocol Synopsis Section 1.3. 
5.3 Exclusion Criteria 
Please refer to Protocol Synopsis Section 1.3. 
6 Investigational Medicinal Product 
6.1 Production, Packaging and Labeling 
ABNCoV2 drug product is released by Bavarian Nordic A/S, DK. 
Address: 
Bavarian Nordic A/S 
 
 
 
The packages and vials of ABNCoV2 vaccine are labeled according to regulatory requirements. 
Vials contain at least 100 μg in 0.3 mL. 
For dilution buffer phosphate buffered saline (PBS) is used and released by Bavarian-Nordic A/S, 
DK. The packages and vials of dilution buffer are labeled according to regulatory requirements. 

 
 
 
 
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6.2 Shipment, Storage and Handling 
Usage of the investigational medicinal product (IMP) is only allowed upon final approval of all 
shipment relevant paperwork by BN or its authorized designee. Only subjects enrolled in the trial 
may receive IMP. 
ABNCoV2 vaccine and dilution buffer PBS (phosphate buffered saline) will be shipped 
separately and temperature controlled and monitored to the CTS. Once at the site, the package 
should be handed over to the personnel in charge of IMP preparation (e.g., the pharmacist). Site 
personnel are responsible for proper storage of IMP upon receipt. All IMP must be stored in a 
secure, environmentally controlled and monitored area in accordance with the labelled storage 
conditions with access limited to the Investigator and authorized site staff. 
ABNCoV2 vaccine is shipped at -20°C and must be stored frozen at -20°C (±5°C). 
PBS has to be shipped and stored refrigerated at +2°C to +8°C .Details on shipment, storage and 
handling of the IMP (and comparable information for the diluent to be used for Group 3) are 
provided in the pharmacy manual. 
6.3 Preparation, Administration and Dosage 
The preparation and administration of the vaccine will be performed by authorized personnel 
only. The vaccine is administered IM into the deltoid muscle of the upper arm (preferably the 
non-dominant arm). 
Trial specific details on preparation, dilution (for Group 3) and administration of the ABNCoV2 
vaccine are provided in the pharmacy manual. 
6.4 Accountability and Disposal 
Used (if allowed by institutional policy) and unused vials of all IMP need to be retained in a 
place with limited access until appropriate drug accountability has been performed. Drug 
accountability must be documented whenever the IMP is either prepared or administered. 
BN will provide a Drug Accountability Log for recording receipt, dispensation, and destruction 
of IMPs (see separate pharmacy manual). Alternative systems used to track drug accountability 
are acceptable for use in the trial provided the aforementioned items are adequately captured and 
records are available for review during scheduled monitoring visits to the site. 
After drug accountability has been performed, used and unused vials should either be returned to 
the designated drug depot, a vendor selected by BN or discarded according to local regulations. 

 
 
 
 
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Destruction or return of IMP must be agreed upon with BN and appropriately documented. 
Documentation should be reviewed and signed off by the pharmacist and Clinical Research 
Associate (CRA) assigned to monitor the site. 
Sites are responsible for the proper destruction and disposal of used needles and syringes, which 
should be performed according to local regulations. If local disposal is not possible, used clinical 
supplies may be returned to BN or to the designated drug depot after prior consultation with BN. 
7 Assessment of Immunogenicity 
The immunogenicity of the vaccine will be assessed by measuring humoral and cellular immune 
responses on collected serum and peripheral blood mononuclear cells (PBMC) samples. 
Immunogenicity testing will be performed at 
 and 
at contracted laboratories, where applicable. Testing standard operating procedures (SOPs), 
effective at the time of testing will be filed in the electronic Trial Master File. 
The procedures for collection, preparation, storage and shipment of specimens for 
immunogenicity testing (serum and PBMC) are specified in separate study-specific instructions, 
which will be provided to the investigators/CTS personnel as well as to the processing 
laboratories before recruitment commences. Additionally, investigators and CTS staff will be 
trained in the procedures during the investigator meeting/site initiation visit. 
7.1 Humoral Immune Response 
Serum samples will be collected from subjects as outlined in the trial procedure schedule in 
Section 1.4. Samples for immunogenicity testing will be obtained at the vaccination visits will be 
drawn prior to vaccination. 
SARS-CoV-2 specific antibody responses will be assessed in trial subjects using enzyme-linked 
immunosorbent assay (ELISA; total antibodies) and neutralization tests (neutralizing antibodies). 
7.2 Cellular Immune Response 
PBMC samples will be collected as outlined in the trial procedure schedule in Section 1.4. 
Samples for immunogenicity testing obtained at the vaccination visits will be drawn prior to 
vaccination. 
SARS-CoV-2 specific cellular responses will be assessed in vaccinated subjects, e.g., using an 
Interferon-J / Interleukin-4 enzyme-linked immune spot technique (ELISPOT). 

 
 
 
 
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7.3 Future Use of Lab Specimen 
Specimens remaining after completion of immunogenicity testing as per protocol will be stored 
for possible future research and analysis supporting the licensure path of ABNCoV2 vaccines. 
Future testing will facilitate the bridging of trial results to animal immunogenicity results and/or 
to immune response data collected from subjects vaccinated with other COVID-19 vaccines. 
Further, remaining samples might be used for assay development and controls. Subjects will be 
invited to consent to storage/future use of samples and will be informed about data protection 
measures. Specimens will be stored in BN’s secured laboratory area 
, or at 
an external storage facility in a coded, pseudonymized manner to ensure data protection. Genetic 
testing will not be performed. 
8 Safety and Reactogenicity 
Safety will be monitored by collection of medical history, performing physical examinations 
including vital signs, when appropriate, electrocardiogram (ECG) and routine laboratory 
measurements (including pregnancy testing and counseling on avoidance of pregnancy for 
WOCBP) as well as by evaluating local and general solicited AEs and unsolicited AEs. AESIs 
are defined as per section 8.6 and are following the same reporting workflow as SAEs. 
8.1 Definitions 
8.2 Medical History 
Symptoms, relevant laboratory findings and ongoing medical conditions present before and/or at 
SCR will be documented as medical history. 
8.3 Adverse Events 
AEs are defined as any untoward medical occurrence in a subject after signature of the ICF and 
which does not necessarily have a causal relationship associated with the administration of an 
IMP. Any new signs, symptoms, laboratory findings or changes in health starting after ICF 
signature are documented in the subjects’ records and the AE section of the eCRF (for data 
collection requirements for screen failures see Section 5). AEs are recorded based on unsolicited 
and solicited questioning (Section 8.4 and 8.5). 
8.4 Unsolicited AEs 
Unsolicited AEs are defined as AEs which are not pre-listed on the memory aid card. Adverse 
events (e.g., feeling of ill-health, subjective symptoms and objective signs, intercurrent diseases, 
accidents, etc.) observed by the investigator and/or reported by the subject must be recorded in 
the eCRF regardless of the assessment of causality in relationship with the IMP/MP. 

 
 
 
 
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After the first vaccination, abnormal laboratory findings assessed as being clinically significant 
by the investigator are to be documented as AEs. In addition, after first vaccination abnormal 
laboratory findings fulfilling the Grade 3 or Grade 4 criteria according to the toxicity scale 
(Appendix 1) are to be documented as AEs in the eCRF, regardless of whether they are 
considered clinically relevant or not. For lab values fulfilling the Grade 3 or Grade 4 criteria, the 
decision to repeat the labs is left to the discretion of the PI. Toxicity grade and seriousness of an 
AE will be assessed separately, i.e., a Grade 3 or Grade 4 AE will not automatically be regarded 
as serious. 
The investigator should ask the subjects if they have experienced any AEs since their last visit. 
All intercurrent diseases reported by the subject need to be recorded by the investigator in the 
appropriate section of the eCRF. 
Any AEs or abnormal laboratory findings starting/reported during the screening phase, i.e., after 
informed consent is given but before the first vaccination, are considered as pre-treatment AEs. 
8.5 Solicited AEs 
In this clinical trial protocol solicited AEs are defined as all symptoms specifically listed in the 
memory aid provided to the subjects following each vaccination. After vaccination, the subjects 
are requested to monitor and record local symptoms (i.e., erythema, swelling, induration, pruritus 
and pain at the injection site) as well as general symptoms (i.e., body temperature 
increase/pyrexia, headache, chills, myalgia, nausea and fatigue) in the memory aid daily for the 
day of vaccination and the following 7 days (Days 1 to 8 following vaccination, 8-day period). If 
symptoms persist at Day 8, daily symptoms and temperature will continue to be measured and 
documented each day until resolved. 
8.6 SAEs and AESIs 
An SAE is any untoward medical occurrence that: 
x 
Results in death 
x 
Is life-threatening 
The term “life-threatening” in the definition of “serious” refers to an event in which the 
subject was at risk of death at the time of the event; it does not refer to an event which 
hypothetically might have caused death, if it were more severe. 
x 
Requires in-patient hospitalization or prolongation of existing hospitalization 
x 
Results in persistent or significant disability or incapacity 
x 
Results in a congenital anomaly or birth defect 

 
 
 
 
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x 
Is an otherwise important medical event, e.g., leads to suspicion of transmission of an 
infectious agent. 
Medical and scientific judgment should be exercised in deciding whether expedited reporting is 
appropriate in other situations, such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above. These should also 
usually be considered serious. 
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. 
Adverse Events of Special Interest (AESIs) are adopted as per the Safety Platform for 
Emergency vACcines (SPEAC) Project generated list of AESI for safety monitoring (accessible 
via https://brightoncollaboration.us/covid-19/) based on the following criteria: 
1) known association with immunization or a specific vaccine platform; 
2) theoretical association based on animal models; 
3) occurrence during wild-type disease as a result of viral replication and/or immunopathogenesis 
This list is updated on a quarterly basis and the current effective list of AESIs is applicable for 
this trial. 
All AEs are collected from signing of ICF, however should not be considered by investigator to 
be an AESI unless occurring since receipt of first vaccination. 
8.7 Relevant Medical History 
Relevant medical history will be self-reported and documented at SCR and will focus particularly 
on any important diseases and in case of infections or tumors, the pathogen involved or the 
pathological diagnosis, if available. In particular, subjects with prior COVID-19 infection need to 
include the infection and dates in the medical history section of the eCRF. Additionally, 
laboratory reports need to be documented during SCR. All ongoing conditions for which the 
subjects are taking medications, and/or which may exacerbate during the trial period should be 
considered as important. Special attention should be given to history of prior allergic reactions, 
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8.8 Prior and Concomitant Medication 
All concomitant (ongoing) medication except homeopathic substances and dietary supplements 
must be recorded in the subject’s medical record and in the eCRF including information about the 
indication, dosage regimen, and the onset and end of treatment. 
The following medications taken within 3 months prior to SCR will also be recorded in the eCRF 
and the subjects medical record: vaccines (e.g., influenza/pneumococcal), corticosteroids (via any 
route of administration), other immune-modulating drugs, immunoglobulin and/or any blood 
products, investigational drugs and depot preparations which are still active at the date of SCR. In 
addition, subjects with previous SARS-CoV-2 vaccination will include the specific vaccine 
received by dose and date in the eCRF, regardless of the time elapsed prior to SCR. 
8.9 Prohibited Medications 
Prohibited medication or medication where washout periods need to be adhered to are (see also 
eligibility criteria in Section 1.3): 
x 
Vaccination with any licensed live vaccine within 30 days prior to first or after last trial 
vaccination or any licensed inactivated vaccine within 14 days prior to first or after last trial 
vaccination. 
x 
Start of chronic systemic administration (defined as more than 14 days of > 5 mg 
prednisone [or equivalent]) per day or any other systemic use of immune-modifying drugs 
during a period starting from 3 months prior to first administration of the trial vaccine and 
ending at the last visit of the active trial phase. The use of topical, inhaled, ophthalmic and 
nasal corticoids will be permitted. 
x 
Administration of immunoglobulins and/or any blood products during a period starting 
from 3 months prior to first administration of the trial vaccine and ending at the last visit of 
the active trial phase. 
x 
Use of any investigational or non-registered drug or vaccine other than the trial vaccine 
within 30 days preceding the administration of the trial vaccine, or planned administration 
of such a drug during the trial period until the FU Visit 3 months after the last vaccination 
visit for Group 1, or 24 months after last vaccination visit for Groups 2 and 3. 
x 
In case official guidelines require booster vaccinations to maintain valid COVID-19 
vaccination certificates, approved booster vaccinations for SARS-CoV-2 are allowed for 
Groups 2 and 3 within the follow-up period, however subjects will be withdrawn from 
further follow up. 

 
 
 
 
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8.10 Physical Examination 
Complete physical examination 
A complete physical examination (excluding breast, genital, and rectal examinations) will be 
performed at SCR. The examination includes a review of major organ systems as well as body 
height and weight. The examination should be directed at finding evidence of any infections, 
tumors and lymphadenopathy (a grading scale for lymphadenopathy is included in Appendix 2). 
In addition, auscultation of the heart and lungs will be performed to check specifically for signs 
of any heart condition or respiratory disorders. 
Any clinically significant findings at the baseline physical examination will be recorded as 
medical history events. The only data captured in the eCRF for the physical examination itself 
will be the date it was performed. Any new or worsening clinically significant findings post- 
treatment will be captured as AEs. 
Targeted physical examination 
A targeted physical examination, guided by any signs or symptoms previously identified or any 
new symptoms that the subject has experienced since the last visit, is required according to the 
trial schedule (Section 1.4). In addition, auscultation of the heart and lungs will be performed to 
check specifically for signs of any heart condition. 
Clinically significant findings from the active trial phase physical examinations will be recorded 
as AEs. 
8.11 Vital Signs 
At SCR and every other trial visit as defined in the trial schedule (Section 1.4), blood pressure 
and pulse rate will be taken after the subject has been sitting upright for approximately 2 minutes. 
Body temperature will be measured orally. Height and weight will be collected at SCR. 
8.12 Unsolicited AEs 
All intercurrent diseases reported when the investigator actively inquires the subject will be 
documented and all required details (e.g., start and stop date, intensity) will be assessed. 
Unsolicited AEs will be reported in the subject’s medical record and respective section of the 
eCRF (requirements for screen failures see Section 12.1). 
Unsolicited AEs will be assessed and documented from ICF signature through EAP, and if 
ongoing at that time followed until resolution or until the subject’s last trial visit, at the latest. 
SAEs and AESIs will be collected through the end of the trial, including during the FU period. 

 
 
 
 
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SAEs and AESIs will be assessed and documented at all trial visits. (S)AEs would only be 
considered as AESIs once subject has received first vaccination. SAEs and AESIs will be 
followed-up until resolution or achievement of stable clinical conditions. 
Assessment of Intensity 
For all unsolicited AEs not represented in the Toxicity Grading Scale for Healthy Adult and 
Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA, 2007), the 
maximum intensity will be based on the following descriptions: 
 
Grade 1 
An AE which is easily tolerated by the subject, causing minimal discomfort and 
not interfering with daily activities. 
Grade 2 
An AE which is sufficiently discomforting to interfere with daily activities, but 
does not require medical intervention (non-narcotic pain reliever or other 
nonprescription medication are not considered “medical intervention” for this 
purpose). 
Grade 3 
An AE which prevents daily activities and which requires medical intervention 
(non-narcotic pain reliever or other nonprescription medication are not considered 
“medical intervention” for this purpose) 
Grade 4 
Life-threatening, or disabling. 
 
Assessment of Causality 
The relationship between the occurrence of an AE and the IMP will be assessed using the 
categories presented below. For expedited reporting and all other purposes, the categories “none” 
and “unlikely” will represent no evidence or argument to suggest a causal relationship, while 
“possible”, “probable” and “definite” will be seen to convey that there is evidence or argument to 
suggest a causal relationship. To ensure reporting, all AEs without a causality assessment from 
the investigator will preliminarily be classified as “possible”. 
In terms of binary causality assessments unlikely and not related in clinical trials is lumped to 
“not related” whereas other causality assessments as per below are lumped to “related”. 
 
Not 
related 
The time interval between administration of the IMP and the occurrence or 
worsening of the AE rules out a relationship, and/or alternative cause is established 
and there is no evidence of a (concomitant) causal connection with or worsening 
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Unlikely 
The time interval between administration of the IMP and the occurrence or 
worsening of the AE makes a causal relationship unlikely, and/or the known effects 
of the IMP or substance class provide no indication of a (concomitant) causal 
connection with or worsening caused by the IMP and there is another cause which 
serves as an adequate explanation, and/or although the known effects of the IMP or 
substance class make it possible to derive a plausible causal chain with regard to a 
(concomitant) causal connection or worsening, however, another cause is 
considerably more likely, and/or another cause of the AE has been identified and a 
(concomitant) causal connection with or worsening caused by the IMP is unlikely. 
Possible 
A plausible causal chain with regard to a (concomitant) causal connection with / 
worsening of the AE can be derived from the pharmacological properties of the IMP 
or substance class. However, other approximately equally likely causes are known, 
or although the pharmacological properties of the IMP or substance class provide no 
indication of a (concomitant) causal connection with / worsening of the AE, there is 
no other known cause which provides an adequate explanation. 
Probable 
The pharmacological properties of the IMP or substance class, and/or the course of 
the AE after discontinuation of the IMP and possible subsequent re-exposure, and/or 
specific findings (e.g., positive allergy test or antibodies against the IMP / 
metabolites) suggest a (concomitant) causal connection with / worsening of the AE 
resulting from the IMP, however another cause cannot completely be ruled out. 
Definite 
The pharmacological properties of the IMP or substance class and/or the course of 
the AE after discontinuation of the IMP and possible subsequent re-exposure, and/or 
specific findings (e.g., positive allergy test or antibodies against the IMP / 
metabolites) definitely indicate that there is a (concomitant) causal connection with / 
worsening of the AE resulting from the IMP and there are no indications of other 
causes. 
8.13 Solicited AEs 
After the vaccination, subjects receive a memory aid to record solicited local and general AEs 
most likely to occur on the day of vaccination and the following 7 days (Days 1 to 8 following 
vaccination, 8-day period). 
All solicited symptoms observed after vaccination with details concerning the intensity and the 
course of the symptom should be documented in the memory aid. The CTS will collect the 
memory aid at the following visit, review the memory aid with the subject, and transfer the 
results to the eCRF and the subject’s medical record. The investigator’s assessment of the 
symptoms will also be recorded in the eCRF including causality (for solicited general AEs), 

 
 
 
 
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seriousness, outcome, action taken with vaccine, and any intervention required. Local and general 
symptoms still ongoing after 8 days will continue to be measured and documented each day until 
resolved. 
To standardize procedures uniform rulers will be handed out to subjects for measurements of 
erythema, swelling and induration diameters, as will digital thermometers for oral measurements 
of body temperature. 
In case of severe and unexpected local and/or general reactions, the subject should be instructed 
to contact the trial physician outside of scheduled trial visits. 
8.14 Solicited Local AEs 
The solicited local symptoms erythema, swelling, induration, pruritus and pain at the injection 
site are to be documented in the memory aid by the subjects. 
Assessment of Intensity 
Injection site erythema, swelling, and induration will be assessed based on the longest diameter 
as measured by the subject in mm and recorded in the memory aid. Subjects are asked to 
document the solicited local AEs in the memory aid as described in Table 2 below. 
Table 2 
Grading of Local Symptoms from the Subject’s Memory Aid 
 
MedDRA coded Preferred Term 
Local Adverse Events 
Grade 
Severity 
Injection site erythema, Injection site 
swelling, and Injection site induration 
(longest diameter measured in mm) 
0 
0 mm 
1 
<30 mm 
2 
– <100 mm 
3 
mm 
Injection site pruritis 
0 
Absent 
1 
Mild 
2 
Moderate 
3 
Severe 
Injection site pain 
0 
Absent 
1 
Painful on touch 
2 
Painful when limb is moved 
3 
Spontaneously painful/prevents normal activity 
Assessment of Causality 
Solicited local AEs are defined as being related to the vaccine. 

 
 
 
 
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8.15 Solicited General AEs 
The solicited general symptoms body temperature, headache, myalgia, nausea, chills and fatigue 
are to be documented in the memory aid by the subjects. 
Assessment of Intensity 
Subjects are asked to document the solicited general AEs in the memory aid as described in Table 
3 below. In the subject’s memory aid, the grading of symptom intensity is described in basic, 
easily understood language based on the following descriptions: 
Table 3 
Grading of General Symptoms from the Subject’s Memory Aid 
 
MedDRA coded Preferred Term 
General Adverse Events 
Grade 
Severity 
Body temperature (oral) * 
0 
<37.5°C (<99.5°F) 
1 
 – <38.0°C – <100.4°F) 
2 
 – <39.0°C – <102.2°F) 
3 
 – <40.0°C – <104.0°F) 
4 
& ) 
Headache, Myalgia, Nausea, Chills and 
Fatigue 
0 
None 
1 
Mild: easily tolerated, minimal discomfort 
and no interference with daily activity 
2 
Moderate: Some interference with daily 
activity 
3 
Severe: Prevents daily activity 
*Pyrexia is defined as oral WHPSHUDWXUH& ) 
 
Assessment of Causality 
Causal relationship between solicited general AEs and the vaccine will be assessed by the 
investigator using the same categories as for unsolicited AEs (see Section 8.12). 
8.16 Safety Laboratory Measurements 
The intensity of laboratory/systemic toxicities measured quantitatively will be graded according 
to the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials (FDA, 2007). The laboratory values provided in this toxicity 
grading scale serve as guidelines and are dependent upon institutional parameters. Institutional 
specific toxicity gradings will be included in site specific manuals as needed. 

 
 
 
 
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Safety laboratory is determined at SCR and V3 (one-dose vaccination schedule) or at SCR, V3 
and V6 (two-dose vaccination schedule) and at any other visit(s) if clinically indicated. If the 
safety laboratory measurements are performed at a local laboratory, the laboratory normal ranges 
are provided by the safety laboratory and are filed in the Investigator File. Safety laboratory 
parameters to be evaluated are: 
Hematology: 
Red blood cell count, hemoglobin, total and differential White Blood Cell count (WBC), platelet 
count, Hematocrit, mean corpuscular/cell volume (MCV), mean corpuscular/cellular hemoglobin 
(MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell distribution 
width (RDW) are routinely performed as part of the complete blood cell count and will be 
included in the laboratory report. 
Serum chemistry: 
Total bilirubin, Alkaline Phosphatase (AP), Aspartate Aminotransferase (AST), Alanine 
Aminotransferase (ALT), serum creatinine, sodium, potassium, calcium, CRP. 
Pregnancy test: 
$ȕ-KXPDQFKRULRJRQDGRWURSLQȕ-HCG) pregnancy test will be conducted for all WOCBP at 
SCR and prior to each vaccination V1 (one-dose vaccination schedule) or V1 and V4 (two-dose 
YDFFLQDWLRQVFKHGXOH$W6&5DVHUXPȕ-HCG pregnancy test will be performed; all other 
SUHJQDQF\WHVWVZLOOEHFRQGXFWHGDVXULQHȕ-HCG tests. 
Virology: 
The following parameters will only be evaluated during the screening period for assessment of 
inclusion/exclusion criteria: 
Human immunodeficiency virus antibody test (anti-HIV) 
HBsAG 
HCV 
Severe Acute Respiratory Syndrome Coronavirus 2 Testing: 
SARS-CoV-2 specific antibody test (at SCR only) 
SARS-CoV-2 infection test (according to trial schedule) 

 
 
 
 
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8.17 Cardiac Assessment 
Electrocardiogram (ECG): 
A standard 12-lead ECG will be taken at the SCR. At any other visit an ECG is only performed if 
clinically indicated. For unclear ECGs the investigator can obtain ECG over-read by a local 
cardiologist. 
The investigator will assess the clinical significance for abnormal ECGs. Interpretation support 
for SCR ECGs is provided in Appendix 3: Interpretation Support for Assessment of SCR ECGs. 
8.18 Pregnancy 
As per inclusion criteria, WOCBP must have a negative serum pregnancy test at SCR and a 
negative urine pregnancy test within 24 hours prior to each vaccination. In addition, they must 
have used an acceptable method of contraception for 30 days prior to the first vaccination, must 
agree to use an acceptable method of contraception during the trial, and must avoid becoming 
pregnant for at least 30 days after the last vaccination. Nevertheless, IMP exposed pregnancies 
cannot be excluded with certainty. Subjects who become pregnant prior to the first vaccination 
will be excluded from the trial and are regarded as SCR failure. Subjects who become pregnant 
during the active trial phase (up to and including 1 month [minimum 28 days] after receiving a 
dose of vaccine) must not receive additional doses of vaccine but may continue other trial 
procedures at the discretion of the investigator (see Section 4.7). All reports, where the embryo or 
fetus may have been exposed to the IMP (through maternal exposure) will be followed-up until 
delivery to collect information on the outcome of the pregnancy (see Section 8.21). 
Subjects will be instructed to notify the investigator if it is determined (also after completion of 
the trial) that they became pregnant either during the trial or within 1 month (minimum 28 days) 
after receiving the last vaccine dose. 
8.19 Reporting 
8.20 Reporting of SAE and AESI 
All SAEs (collection starts at signing of ICF) and AESIs (collection starts upon receiving first 
vaccination) occurring throughout the entire course of the trial have to be entered in the eCRF 
within 24 hours of awareness by the investigators, which triggers an autogenerated output to the 
Drug Safety (DS)/PV Department of the contract research organization (CRO). 
In case the eCRF is unavailable, the SAE and AESI report form is sent via email to the DS/PV 
Department of the CRO within 24 hours of becoming aware of the SAE or AESI. 

 
 
 
 
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Serious adverse events and AESIs should be sent to: 
 
Cc: 
 
The investigator should not delay reporting because of missing information. Nonetheless, the 
report should be as complete as possible. This initial notification should include, as a minimum, 
sufficient information to permit identification of the following: 
• the reporter (investigator’s name and contact information) 
• the subject 
• involved trial medication 
• AE(s) 
• seriousness criterion 
• date of onset 
BN/CRO is responsible for expedited as well as periodic reporting to the involved regulatory 
authorities according to applicable laws and guidelines, and for forwarding final safety reports to 
the clinical CRO. 
Regulatory authorities will be notified as soon as possible but no later than 7 days after first 
knowledge of fatal or life-threatening unexpected SAE with an at least possible relationship to 
the IMP (serious adverse drug reaction [SADR]) and no later than 15 days after knowledge of 
any other unexpected SADR. The same process applies for AESIs. The clinical CRO is 
responsible for reporting to the Ethics Committees or IRBs and HRPO. Figure 2 outlines the 
reporting process and timelines for SAEs and AESIs. 

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yes
No
Is the AE serious?
Investigator reports SAE 
and AESI to eCRF/DS 
within 24 h
Record Event in the 
AE section of the eCRF
AE
yes
Expedited reporting
necessary?
no
SAE and AESI entered 
into safety database
SAE and AESI entered 
into safety database and 
safety reports created
Figure 2 
Algorithm for Reporting of SAEs and AESIs
BN CSPV releases safety reports within
max. 15d/7d to RA (final) and to clinical CRO; for
SUSARs health authority reporting will be by BN RA
Clinical CRO forwards final 
safety reports within max. 
15d/7d to concerned IRBs, 
IECs, MCS-HRPO and
investigators

 
 
 
 
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8.21 Reporting of Pregnancies 
If a subject becomes pregnant during the active trial phase (up to and including 1 month 
[minimum 28 days] after receiving the trial vaccination) this must be recorded on the Pregnancy 
eCRF (or Pregnancy Notification Report Form if EDC unavailable) within 24 hours of the 
investigator becoming aware of the event (Section 8.20). 
A pregnancy will be followed to term, any premature terminations reported, and the health status 
of the mother and child including date of delivery and the child’s sex and weight will be reported 
by the investigator to the CRO DS and BN as soon as possible after delivery by recording 
outcome on the pregnancy eCRF (or Pregnancy Outcome Report Form if EDC unavailable). 
Any event during pregnancy fulfilling the criteria for an SAE or AESI will be reported to the 
CRO DS/PV department (see Section 8.20). However, hospitalization for delivery is a 
prospectively planned hospitalization and is not considered a SAE, per se. 
9 Statistical Considerations 
9.1 Randomization Procedure 
No randomization procedure will be used for this trial. Recruitment will be performed with a run- 
in period including enrollment of 6 subjects into Group 1 and 2 (3 subjects in each). Subjects will 
be vaccinated in a consecutive manner as described in Section 4.1. After completion of V2 and 
positive review of safety data by the DMC, the DMC will allow for the enrollment of all 
remaining subjects. Assignment into Group 1 versus Group 2 and 3 will be based on the subjects’ 
baseline SARS-CoV-2 antibody status. For seropositive subjects the reason for seropositivity will 
be documented: previous COVID-19 infection, mRNA vaccinated, adenovirus-vaccinated, or a 
mix of those. 
Due to the timing of the addition of Group 3, enrollment into Group 2 will be completed prior to 
enrolling subjects into Group 3. Therefore, no randomization will be required for the 
seropositive subjects. 
9.2 Sample Size Calculation 
Group 1: Up to 30 subjects determined to be seronegative for SARS-CoV-2 antibodies at SCR 
will be enrolled in Group 1. 
Group 2: approximately 90 subjects determined to be seropositive for SARS-CoV-2 antibodies at 
SCR will be enrolled in Group 2. 

 
 
 
 
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Group 3: approximately 90 subjects determined to be seropositive for SARS-CoV-2 antibodies at 
SCR will be enrolled in Group 3. 
The primary objective of Group 1 is to estimate the level of neutralizing antibodies 2 weeks after 
the second vaccination. This will be measured by the geometric mean of the neutralizing antibody 
titers and its 95% confidence interval. Based on published data on the peak neutralizing antibody 
titers following vaccination with licensed SARS-CoV-2 vaccines, we assume the standard 
deviation in logarithm 10 (log10) scale will be approximately 0.5. When the sample size is 30, a 
two-sided 95% confidence interval will extend 0.179 from the observed mean in log10 scale. The 
corresponding 95% confidence interval for the geometric mean will be between 132 and 302 if 
the point estimate is 200; it will be between 166 and 377 if the point estimate is 250. The lower 
bound of 132 to 166 is in the similar range of licensed SARS-CoV-2 vaccines (Jin et al., 2021). 
The primary objective for Groups 2 and 3 is to estimate the geometric mean of the ratio of 
neutralizing antibody titers 2 weeks after the single booster vaccination with ABNCoV2 versus 
the pre-booster level. We assume the same standard deviation of 0.5 in log10 scale in both pre- 
booster and post-booster titers; the correlation coefficient between the pre-booster and post- 
booster titers is 0.3; and the distribution of the ratio is log-normal. When the sample size is 90, a 
two-sided 95% confidence interval will extend 0.122 from the observed mean in log10 difference. 
If the observed geometric mean of the ratio is 4 (i.e., a 4-fold increase after booster), the 95% 
confidence interval will be (3.0, 5.3). When stratified by baseline titer subgroups (<median or 
PHGLDQ the lower bound of the 95% confidence interval will be at least 2.7 when the observed 
ratio is 4 with a subgroup size of 45. 
9.3 Multiplicity 
Since there is no hypothesis test in this phase 2 trial, multiplicity is not applicable. 
9.4 Variables 
Please refer to endpoints in Protocol Synopsis Section 1.3. 
9.5 Analysis Population 
The analysis population includes subjects who meet all of the inclusion and none of the exclusion 
criteria as defined separately for the three groups in Section 1.3, e.g., subjects assigned to 
Group 1 must be confirmed seronegative; subjects assigned to Groups 2 and 3 must be confirmed 
seropositive. 
The Safety Analysis Set for all safety variables and population level summaries includes all 
subjects who received at least 1 dose of the ABNCoV2 vaccine. 

 
 
 
 
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The Immunogenicity Analysis Set for immunogenicity variables and population level summaries 
includes all subjects who are in the Safety Analysis Set and have at least 1 post-vaccination 
neutralizing antibody titer result. A data review meeting will determine if any protocol violations 
will affect the immunogenicity outcomes and these subjects will be removed from the analysis 
set. 
9.6 Analysis Methods 
9.7 Primary Estimand 
9.8 Population Level Summary 
Group 1: Geometric mean of SARS-CoV-2 neutralizing antibody titers at 2 weeks after the boost 
vaccination. 
Groups 2 and 3: Geometric mean of the fold-increases, defined as the ratio of SARS-CoV-2 
neutralizing antibody titer at 2 weeks divided by the neutralizing antibody titer at baseline (last 
measurement prior to ABNCoV2 vaccination). 
9.9 Intercurrent Events 
The following are considered intercurrent events: 1) development of COVID-19 symptoms prior 
to 2 weeks after the last vaccination (Week 6 in Group 1 and Week 2 in Groups 2 and 3) and 
having a positive test for SARS-CoV-2 infection, and 2) discontinuation due to AEs from either 
the second vaccination (Group 1) or the trial. For the primary estimand, the second intercurrent 
event is not considered as having an impact on the SARS-CoV-2 neutralizing antibody levels and 
therefore the “treatment policy” strategy will be used. Subjects who come in contact with the 
virus can have significant interference with the SARS-CoV-2 neutralizing antibody levels and 
thus will be excluded from the primary analysis. This is equivalent to the “while on treatment” 
strategy. 
9.10 Primary Analysis 
The geometric mean of SARS-CoV-2 neutralizing antibody titers (Group 1) and fold increases 
(Groups 2 and 3) 2 weeks after the last vaccination will be summarized along with their 95% 
confidence intervals. The arithmetic means and the corresponding 95% confidence intervals on 
the log10 scale will be calculated using the normal approximation approach. The geometric means 
and the 95% confidence intervals will be obtained by exponentiating the log10 means and 
confidence limits. For Groups 2 and 3, analyses of fold-increases will be performed by baseline 
WLWHUFDWHWRULHVPHGLDQRUPHGLDQWRDFFRXQWIRUWKHH[SHFWHGYDULDWLRQLQWKHEDVHOLQH
neutralizing titer due to the different reasons for seropositivity (i.e., previous mRNA vaccination, 
previous Adenovirus-based vaccination, or previous COVID-19 infection). As the Groups 2 and 

 
 
 
 
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3 baseline titer distributions are assumed to be the same, the median baseline neutralizing titer 
category will be derived from the median of both groups. This will allow for comparability 
between the geometric fold-increases by dose level (i.e., 100 μg vs. 50 μg). 
9.11 Sensitivity and Supportive Analyses 
The primary analysis will be supported by descriptive summaries (geometric means, 95% 
confidence intervals of the geometric means and median) for each time point (pre- and post- 
vaccination). Response rates, with response being defined as SARS-CoV-2 neutralizing antibody 
titers above the limit of quantification in Group 1, or having an at least 2-fold or 4-fold increase 
from baseline in Groups 2 and 3, respectively, will also be summarized and corresponding 95% 
confidence intervals will be calculated using the Clopper-Pearson method. For these analyses, 
both the median categories will be used as defined for the primary analysis as well as quartile 
categories from the pooled Group 2 and 3 baseline neutralizing titer data. 
Because the window between vaccination and the primary endpoint measurement is short, the 
number of subjects with missing data due to the intercurrent event is expected to be small. If 
there are any, missing data will be imputed using the multiple imputation method as a sensitivity 
analysis. 
The primary analyses will also be performed by age groups as supportive analyses: 18 to 
<50 years, 50 to <65 years, 65 to <75 years, and  years. 
9.12 Secondary Estimands 
9.13 Population Level Summary 
Percent of subjects reporting any SAE or AESI assessed as related to trial vaccine within 8 days 
after vaccination, and percent of subjects reporting any Grade 3 or higher AE assessed as related 
to trial vaccine within 8 days after vaccination. 
9.14 Intercurrent Events 
The second intercurrent event is relevant for this estimand. If it is confirmed by the investigator 
that the subject discontinues the trial within 8 days after vaccination due to AEs, the subject is 
considered having a related SAE/AESI/Grade 3 or higher AE regardless of the seriousness, 
severity, or causality of the AE for which the subject discontinued. This is consistent with the 
“composite” strategy. 

 
 
 
 
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9.15 Main Analyses 
Percent of subjects reporting any SAE or AESI and percent of subjects reporting any Grade 3 or 
higher AE assessed as related to trial vaccine within 8 days after any vaccination will be 
summarized by group and the 95% confidence interval will be calculated using the Clopper- 
Pearson method. 
9.16 Sensitivity and Supportive Analyses 
If any subject discontinues the trial within 8 days after vaccination due to AEs, a sensitivity 
analysis will be performed using the “treatment policy” strategy to handle the intercurrent event, 
where the subject will not be considered having a related SAE/AESI/Grade 3 or higher AE 
assessed as related to trial vaccine. 
9.17 Exploratory Endpoints 
Besides the primary and secondary estimands, the SARS-CoV-2 neutralizing antibody titers will 
also be assessed at 2 weeks and 4 weeks after prime vaccination, and at 1 week, 4 weeks and 
3 months after boost vaccination for Group 1. For Groups 2 and 3, the neutralizing antibody titers 
will also be assessed at 1 week, 4 weeks, 3 months, 6 months, 1 year and 2 years after 
vaccination. These data will be summarized descriptively by geometric means and 95% 
confidence intervals for each time point within each of the three groups. For Groups 2 and 3, 
analyses will be performed by the baseline neutralizing titer category (<median or PHGLDQ7KH
data will also be presented by age subgroups. 
SARS-CoV-2 neutralizing antibody titers against various variant strains circulating at the time of 
analysis at 2 weeks after last vaccination for all groups will be summarized similarly. 
Total antibody titers measured by ELISA and cellular immune responses measured by ELISPOT 
will also be summarized by geometric means and their 95% confidence intervals similar to the 
summaries performed for the neutralizing antibody titers. 
The geometric means and 95% confidence intervals will also be plotted as a function of time by 
group for each of the three groups. 
Response rates, with response being defined as SARS-CoV-2 neutralizing antibody titers or total 
antibody titers above the limit of quantification or having an at least 2-fold increase or 4-fold 
increase from baseline in Groups 2 and 3, respectively, will also be summarized by time points 
and groups, and the 95% confidence intervals will be calculated using the Clopper-Pearson 
method. 

 
 
 
 
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9.18 Analyses of Safety 
Other safety data will be summarized descriptively. AE data will be coded using the Medical 
Dictionary for Regulatory Activities (MedDRA). Solicited and unsolicited AEs will be 
summarized by system organ class, preferred term, and group. Solicited and unsolicited AEs that 
PHHWFHUWDLQFULWHULDHJ*UDGH*UDGHVHULRXVUHODWHGWRYDFFLQDWLRQZLWKLQRU
days after the first or the second vaccination will be summarized similarly. 
The proportion of subjects testing positive for COVID-19 infection by timepoint and at any time 
post vaccination will be summarized by group. 
Vital signs and safety laboratory data will focus on subject level changes, thus shifts from 
baseline will be summarized by group, and graphical presentations may be used. 
9.19 Timing of Analyses 
9.20 Primary Analysis 
In order to inform the phase 3 trial, a primary analysis of immunogenicity and safety will be 
performed once all subjects have completed the visit for the primary immunogenicity endpoint (2 
weeks after the second vaccination for Group 1 or 2 weeks after the single booster vaccination for 
Groups 2 and 3) or withdrawn early from the trial, and at least the neutralizing antibody testing 
results are available. Trial data will be cleaned through the primary immunogenicity analysis 
timepoint, and a data review meeting will be conducted to review the key trial data for the 
primary analysis and determine the subjects to be excluded from the Immunogenicity Analysis 
Set. 
Reporting will include the analysis of the primary and secondary endpoints (as available), as well 
as total antibody data and neutralizing antibody titers against various variant strains at 2 weeks 
after last vaccination. Additionally, demographics and disposition data through the time of 
analysis will be summarized to describe the population included in the primary analysis. The 
results of the primary analyses from the primary and secondary endpoints are not expected to 
change for later reporting. Further details of the summaries to be included in the primary analysis 
will be included in the SAP. 
9.21 Final Trial Analysis 
The final analysis for the trial will occur once all subjects have completed the follow up visits or 
withdrawn early for the trial, and the database has been locked. Analyses of all endpoints will be 
included at this time for the full clinical study report. Results from the primary analysis is not 
expected to change, but rather the remaining immunogenicity, safety, and disposition results will 

 
 
 
 
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be added to the primary analysis results. Any changes in the data or planned analyses from the 
primary analysis will be fully documented. 
10 Ethical Aspects 
10.1 Ethical and Legal Regulations 
The PI is to ensure that this clinical trial is conducted in complete accordance with the provisions 
of the 2013 version of the Declaration of Helsinki, the national laws and other guidelines for the 
conduct of clinical trials like the ICH GCP to guarantee the greatest possible subject protection. 
10.2 Approval by IEC/IRB 
The clinical trial protocol must be reviewed by the competent IEC/IRB according to the national 
laws of the respective CTS before the first subject is included in this trial. 
If one of the investigators is a member of one of these committees, he/she may not vote on any 
aspect of the review of this protocol. 
The Sponsor will assure that the IEC/IRB is informed of any amendment to the protocol and any 
unanticipated problems involving risks to human subjects included in the trial. Such information 
will be provided to the IEC/IRB at intervals appropriate to the degree of subject risk involved, but 
not less than once a year. Copies of all correspondence between the investigator and the IEC/IRB 
must be forwarded immediately to the Sponsor. In case of withdrawal of IEC/IRB approval of the 
trial, the Sponsor has to be contacted immediately by facsimile, e-mail or telephone. 
10.3 Confidentiality and Data Protection 
The PI of the respective CTS is obliged to ensure pseudonymity of the subject. He/she has to 
make sure that all documents including eCRFs provided to third parties (e.g., in the course of a 
marketing authorization procedure) contain no subject names. 
Only a subject and site number may identify subjects. Their name or clinic and subject’s medical 
record number may not be used. The PI keeps separate confidential subject logs for trial 
recruitment which allows subject numbers to be matched with names and addresses of subjects at 
any time. Documents not meant to be passed on to third parties have to be stored securely by the 
PI. 
Information collected in the course of the trial may be made available to persons directly 
involved in this trial (PI and his staff members, monitors, statisticians) or to persons authorized 
by the Sponsor or to authorities. The Sponsor of the trial will only receive pseudonymized data 
for analysis. 

 
 
 
 
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11 Informed Consent 
The ICF and process must comply with ICH GCP guidelines, as well as specific national 
regulations and/or local laws in the countries where the trial is conducted and must be approved 
by the appropriate IEC/IRB. 
The ICF will document the trial-specific information the Investigator or his/her designee 
(designee must be listed on the Delegation of Authority log) provides to the subject and the 
subject’s agreement to participate. The Investigator, or designee, must explain in terms 
understandable to the subject the purpose and nature of the trial, trial procedures, anticipated 
benefits, potential risks, possible adverse effects, and any discomfort participation in the trial may 
entail. 
Subjects must be informed unequivocally that they may refuse participation in the trial and that 
they may withdraw from the trial at any time and for whatever reason and that withdrawal of 
consent will not affect their subsequent medical treatment or relationship with the treating 
physician. 
Subjects also consent to authorize the monitor, quality assurance personnel and regulatory 
authorities to inspect source documents for data verification and quality assurance purposes. Such 
verifications will always be conducted at the CTS and under the ethical supervision of the 
investigator. All aspects of the confidentiality of the subject’s data will be guaranteed. 
This ICF process must be documented in the subject’s source record. Each subject must provide a 
signed and dated informed consent before any trial-related (nonstandard of care) activities are 
performed (such as SCR). The initial and any amended signed and dated consent forms must 
remain in each subject’s trial file at the CTS and be available for verification by trial monitor, 
Sponsor/CRO auditor or competent regulatory authorities at any time. A copy of each signed 
consent form must be given to the subject at the time that it is signed by the subject. 
12 Electronic Case Report Forms and Retention of Records 
12.1 Electronic Case Report Forms 
Electronic case report forms (eCRFs) will be used to collect the clinical trial data. 
All eCRFs are to be filled out completely by authorized CTS personnel. It is the Investigator’s 
responsibility to ensure that all subject data entered in the eCRF (including discontinuations or 
changes in trial vaccine or other medications) are accurate, complete, legible and supported by 
the subject’s medical records. The Investigator attests to this by providing electronic signature 
within the EDC system. 

 
 
 
 
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The eCRFs for any subject leaving the trial should be completed at the time of the final visit or 
shortly thereafter. For subjects not fulfilling the eligibility criteria the minimum information 
documented in the eCRF is the ICF information, demographics, and reason for screen failure. 
The eCRFs exists within an electronic data capture (EDC) system with controlled access 
managed by BN or its authorized representative for this trial. Trial staff will be appropriately 
trained in the use of eCRFs and application of electronic signatures before the start of the trial 
and before being given access to the EDC system. Original data and any changes of data will be 
recorded using the EDC system, with all changes tracked by the system and recorded in an 
electronic audit trail. After database lock, the Investigator will receive a copy of the subject data 
(e.g., paper, CD-ROM or other appropriate media) for archiving at the CTS. 
12.2 Retention of Records 
The Investigator/trial staff must maintain adequate and accurate records to enable the conduct of 
the trial to be fully documented and the trial data to be subsequently verified. All essential 
documents, as listed in ICH GCP guidelines, will be retained by the Investigator for at least 
2 years after the date the last marketing application is approved for the drug in the indication 
being investigated and until there are no pending or contemplated marketing applications; or, if 
no application is to be filed or if the application is not approved for such indication, until 2 years 
after formal discontinuation of clinical development of the drug. 
The Investigator must notify and obtain written approval from BN before destroying any clinical 
trial documents or images (e.g., scan, radiograph, ECG tracing) at any time. The Sponsor will 
inform the Investigator of the date that the trial records may be destroyed or returned to BN. 
Should an Investigator wish to assign trial records to another party, advance written notice must 
be given to the Sponsor. Bavarian Nordic must also be notified in advance and provide express 
written approval of any change in the maintenance of clinical trial documents, should the 
Investigator choose to move trial records to another location. 
If the Investigator cannot guarantee the aforementioned archiving requirements at the CTS for all 
such documents, special arrangements must be made between the Investigator and BN to store 
these documents in secure sealed containers away from the CTS. These documents must be able 
to be returned in their secure sealed containers to the CTS for auditing purposes. 
13 Monitoring of the Trial 
Contract research organization (contact information to be found in the “Responsibilities” section 
in the beginning of this protocol) will be contracted to perform monitoring services according to 
ICH GCP. Monitoring will be conducted according to the monitoring plan which must be 
approved by BN. The monitoring plan will outline the monitoring strategy (including rationale) 

 
 
 
 
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and will specify in detail the items for source data verification and other tasks, to be performed 
by the CRA. 
Monitoring will be conducted through onsite visits with the Investigator and site staff, remote 
monitoring, as well as any appropriate communications by mail, fax, email, or telephone. The 
purpose of monitoring is to ensure that the trial is conducted in compliance with the protocol, 
SOPs, and other written instructions and regulatory guidelines, and to ensure the quality and 
integrity of the data. 
To assure the accuracy of data collected in the eCRFs, it is mandatory that the monitor have 
direct access to all original source documents, including all electronic medical records at 
reasonable times and upon reasonable notice. During the review of source documents, every 
effort will be made to maintain the privacy and confidentiality of all subjects during this clinical 
trial. 
The site needs to maintain records to identify the nature and location of all source documents as 
well as essential documents. 
13.1 Protocol Deviations 
A protocol deviation is any noncompliance with the clinical trial protocol. The noncompliance 
may be either on the part of the participant, the investigator, or the trial site staff. As a result of 
deviations, corrective actions are to be developed by the site and implemented promptly. 
The PI or designee will be responsible for identifying and recording all deviations which are 
defined as isolated occurrences involving a procedure that did not follow the protocol or a 
protocol-specific procedure. All deviations from the protocol and actions taken will be recorded 
in the source data and placed in the trial specific regulatory file. Protocol deviations must be sent 
to the local IEC/IRB per their guidelines. The site PI/trial staff is responsible for knowing and 
adhering to their IEC/IRB requirements. Further details about the handling of protocol deviations 
will be included in a trial specific procedure. 
14 Audits and Inspections 
Site audits may be carried out by the BN quality assurance department or designee at any time 
during or after completion of this trial. All documents pertinent to the trial must be made 
available to the designated auditor. Subject 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 designee. 
In addition, representatives from local, state, or federal regulatory authorities may choose to 
inspect a trial site at any time before, during, or after completion of the clinical trial. The 

 
 
 
 
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Investigator should immediately notify the Sponsor if they have been contacted by a regulatory 
agency concerning an upcoming inspection. In the event of such an inspection, BN will be 
available to assist in the preparation. All pertinent trial data should be made available as 
requested by the Regulatory Authority for verification, audit, or inspection purposes. 
15 Responsibility of the Investigator 
The Investigator should be qualified by education, training, and experience to assume 
responsibility for the proper conduct of the trial, 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 PI agrees to carry out the trial in accordance with the guidelines and procedures outlined in 
this clinical trial protocol. The PI especially consents to strictly adhere to the ethical aspects of 
this protocol (see Section 10). 
Changes to the protocol require written “Amendments to the protocol” and written approval by 
the IEC/IRB and the PI. Changes are allowed only if the trial value is not reduced and if they are 
ethically justifiable. If warranted, the subject information has to be changed accordingly. 
It is within the responsibility of the investigator that the eCRF is completed in a timely manner 
after each subject visit and electronically signed after the subject has completed the trial for each 
subject participating in the trial. 
At the conclusion of the trial, the investigator will return all partially used, unused and empty 
drug containers to the assigned warehouse, a vendor selected by BN or the drug containers will 
be destroyed at the CTS according to local legal requirements. 
The investigator may ask to terminate participation in the trial due to administrative or other 
reasons. If this should be the case, appropriate measures which safeguard the interests of the 
participating subjects must be taken after verification and consultation with the PI. 
The investigator will maintain appropriate medical and research records for this trial, in 
compliance with the ICH E6 Guideline for GCP and regulatory and institutional requirements for 
the protection of confidentiality of subjects. He/she will permit authorized representatives of the 
Sponsor and regulatory authorities to review (and, when required by applicable law, to copy) 
clinical records for the purposes of quality reviews, audits/inspections, and evaluation of the trial 
safety and progress. 
The PI agrees to follow the detailed publication policy included in the clinical trial agreement. 

 
 
 
 
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By signing this protocol, the PI confirms that he/she has read the entire clinical trial protocol, 
agrees to its procedures, and will comply strictly with the formulated guidelines. 

 
 
 
 
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16 References 
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THRANE, S., JANITZEK, C. M., MATONDO, S., RESENDE, M., GUSTAVSSON, T., DE 
JONGH, W. A., CLEMMENSEN, S., ROEFFEN, W., VAN DE VEGTE-BOLMER, M., 
VAN GEMERT, G. J., SAUERWEIN, R., SCHILLER, J. T., NIELSEN, M. A., 
THEANDER, T. G., SALANTI, A. & SANDER, A. F. 2016. Bacterial superglue enables 
easy development of efficient virus-like particle based vaccines. J Nanobiotechnology, 14, 
30. 
TISSOT, A. C., RENHOFA, R., SCHMITZ, N., CIELENS, I., MEIJERINK, E., OSE, V., 
JENNINGS, G. T., SAUDAN, P., PUMPENS, P. & BACHMANN, M. F. 2010. Versatile 
virus-like particle carrier for epitope based vaccines. PLoS One, 5, e9809. 
WALLS, A. C., PARK, Y. J., TORTORICI, M. A., WALL, A., MCGUIRE, A. T. & VEESLER, 
D. 2020. Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein. 
Cell, 181, 281-292.e6. 
WRAPP, D., WANG, N., CORBETT, K. S., GOLDSMITH, J. A., HSIEH, C. L., ABIONA, O., 
GRAHAM, B. S. & MCLELLAN, J. S. 2020. Cryo-EM structure of the 2019-nCoV spike 
in the prefusion conformation. Science, 367, 1260-1263. 
WU, F., WANG, A., LIU, M., WANG, Q., CHEN, J., XIA, S., LING, Y., ZHANG, Y., 
XUN, J., LU, L., JIANG, S., LU, H., WEN, Y. & HUANG, J. 2020. Neutralizing 
antibody responses to SARS-CoV-2 in a COVID-19 recovered patient cohort and their 
implications. medRxiv, 2020.03.30.20047365 

 
 
 
 
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17 Appendices 
Appendix 1: Toxicity Scale for Laboratory Values 
Grade 1 or Grade 2 toxicity is only graded according to “Toxicity Grading Scale for Healthy 
Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA, 2007)” if 
the value is outside of the institutional normal range applicable for this trial. 
Estimating severity grade 
For abnormalities NOT found elsewhere in the Toxicity Tables use the scale below to estimate 
grade of severity: 
 
 
 
Grade 1 
An AE which is easily tolerated by the subject, causing minimal discomfort and 
not interfering with daily activities. 
 
Grade 2 
 
An AE which is sufficiently discomforting to interfere with daily activities, but 
does not require medical intervention (non-narcotic pain reliever or other 
nonprescription medication are not considered “medical intervention” for this 
purpose). 
 
Grade 3 
 
An AE which prevents daily activities and which requires medical intervention 
(non-narcotic pain reliever or other nonprescription medication are not considered 
“medical intervention” for this purpose). 
 
Grade 4 
 
Life-threatening or disabling 
 
Serious or life-threatening AEs 
ANY clinical event deemed by the clinician to be serious or life-threatening should be considered 
a Grade 4 event. Clinical events considered to be serious or life-threatening include, but are not 
limited to: Seizures, coma, tetany, diabetic ketoacidosis, disseminated intravascular coagulation, 
diffuse petechiae, paralysis, acute psychosis, severe depression. 

 
 
 
 
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Appendix 2: Grading Scale for Lymphadenopathy 
A grading scale for lymphadenopathy would apply as follows: 
 
Grade 0 (normal finding): 
No palpable lymph nodes or lymph nodes up to a diameter of 
1 cm, soft, non-tender 
Grade 1 (mild): 
Slightly palpable lymph nodes or lymph nodes up to a diameter 
of 1 cm, bilaterally enlarged lymph nodes, signs of tenderness 
 
Grade 2 (moderate): 
 
Markedly palpable lymph nodes or lymph node diameter 
exceeds 1 cm, bilaterally enlarged lymph nodes, pain, skin 
redness, warmth, limiting instrumental daily life activities 
Grade 3 (severe): 
Markedly palpable lymph nodes or lymph node diameter 
exceeds 2 cm, generalized enlargement of lymph nodes, severe 
pain, general symptoms like fever and sweating limiting self- 
care daily activities 

 
 
 
 
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Appendix 3: Interpretation Support for Assessment of Screening ECGs 
For a clearer and mutual understanding of inclusion criterion #8, the following provides 
clarifying explanations and examples pertaining to eligibility for enrollment. 
Examples of subjects eligible for enrollment: 
x 
Non-specific ST and T wave changes are not considered clinically significant and subject 
can be enrolled. 
x 
Sinus bradycardia which does not require clinical intervention is not considered clinically 
significant and subject can be enrolled. 
x 
Subjects who present with atrial disease which do not require clinical intervention, e.g., a 
pacemaker or drug treatment are allowed to be enrolled, as these can be considered not 
clinically significant. Examples are premature atrial contractions or ectopic atrial beats. 
x 
Occasional premature ventricular contractions which do not require clinical intervention are 
not considered clinically significant and subject can be enrolled. 
x 
First degree AV block or PR interval prolongations are also acceptable as long as they do 
not require clinical intervention, i.e., do not represent an indication for a pacemaker, and 
therefore the condition can be classified as not clinically significant. 
x 
Right or left axis deviation which does not require clinical intervention is not considered 
clinically significant and subject can be enrolled. 
x 
QTc prolongations <500 ms which do not require clinical intervention are not considered 
clinically significant and subject can be enrolled. QTc SURORQJDWLRQV ms which do not 
require clinical intervention should be discussed with the Medical Monitor before 
enrollment. 
Examples of subjects NOT eligible for enrollment: 
x 
Second or third degree atrioventricular block could represent significant heart disease and 
subject should not be enrolled. 
x 
Incomplete left bundle branch blocks could represent significant heart disease and subject 
should not be enrolled. 
x 
Significant ventricular disease represented by complete intraventricular conduction defects 
(complete left or right bundle branch block) must be considered clinically significant and 
subjects presenting with any such condition should not be enrolled. Left anterior or 
posterior intraventricular fascicular blocks or hemiblock could represent ventricular disease 
and subject should not be enrolled. 
x 
ST elevation consistent with ischemia, subject should not be enrolled. 
x 
Two premature ventricular contractions in a row, subject should not be enrolled. 

 
 
 
 
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Appendix 4: Signature Page 
Investigator Signature Page 
Herewith I agree that I have read and fully understand this protocol: 
An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of 
the ABNCoV2 Vaccine in SARS-CoV-2 Seronegative and Seropositive Adult Subjects 
This protocol describes necessary information to conduct the trial. I agree that I will conduct the 
trial according to the instructions given within this protocol. Furthermore, I agree that I will 
conduct this trial according to International Conference of Harmonization of Technical 
Requirements for Registration of Pharmaceuticals for Human Use (ICH) Good Clinical Practice 
(GCP), the 2013 version of the Declaration of Helsinki, as well as applicable local legal and 
regulatory requirements in the respective countries. Additionally, I will follow all applicable 
national regulations requirements (e.g., German Arzneimittelgesetz). I agree that all information 
revealed in this protocol is handled strictly confidentially. 
Additionally, I will permit trial related monitoring, audits, Institutional Review Board (IRB) / 
Independent Ethics Committee (IEC) review and regulatory inspections, providing direct access 
to source data/documents. 
 
 
 
 
 
 
 
 
 
 
 
 
 
(Date) 
 
(Signature) Name, MD 
 
Principal Investigator (PI) 
Address 

 
 
 
 
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Coordinating Investigator Signature Page 
 
 
An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of 
the ABNCoV2 Vaccine in SARS-CoV-2 Seronegative and Seropositive Adult Subjects 
I agree that the protocol was written according to international ethical and scientific quality 
standards (ICH-GCP), in compliance with the 2013 version of the Declaration of Helsinki and 
local legal and regulatory requirements applicable in the respective country. 
 
 
 
 
 
 
 
 
 
 
 
 
 
17-Oct-2021 | 10:03 CEST 
 
 
 
 
(Date) 
 
(Signature) 
 
 
Principal Investigator (PI) 
 
 
 

 
 
 
 
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By signing the protocol: 
Sponsor Signature Page 
An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of 
the ABNCoV2 Vaccine in SARS-CoV-2 Seronegative and Seropositive Adult Subjects 
the undersigned parties agree that the protocol was written according to international ethical and 
scientific quality standards (ICH-GCP), in compliance with the 2013 version of the Declaration 
of Helsinki and local legal and regulatory requirements applicable in the respective country. 
 
 
 
 
 
 
 
 
15-Oct-2021 | 15:53 CEST 
 
Coordinating Author 
and Medical Monitor 
 
 
(Date) 
 
(Signature) 
 
 
Bavarian Nordic GmbH 
15-Oct-2021 | 15:29 CEST 
 
 
 
 
Biostatistician 
 
 
(Date) 
 
(Signature) 
 
 
Bavarian Nordic Inc. 

 
 
 
 
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Appendix 5: Summary of Changes for Amendment#1 to the Clinical Trial 
Protocol 
 
 
An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of 
the ABNCoV2 Vaccine in SARS-CoV-2 Seronegative and Seropositive Adult Subjects 
Date of Edition 2.0: 1-Jul-2021 
 
 
Rationale 
The protocol Edition 2.0 has been created to implement and incorporate revisions requested by 
the Paul Ehrlich Institute (PEI) on 22-Jun-2021. 
Changes 
Changes/ added terms are highlighted in bold letters in the text (table below), deleted terms are 
marked using strikethrough. 
Table 4 
Description 
 
Clinical Trial Protocol Edition 1.0, 
dated 29-Apr-2021 
Previously written: 
Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Changed to: 
1.2 Definitions, page 8 
1.2 Definitions, page 8 
 
Completed vaccination regimen with an 
authorized SARS-COV2 vaccine. “Authorized” 
SARS-CoV2 vaccine refers to authorization status 
at SCR, i.e., subjects can be eligible if they 
previously received investigational vaccines that 
have since been authorized for emergency use or 
granted full market licensure. “Completed” means 
administration of all vaccinations as described in 
the respective label. 
Added to explain definition used in inclusion 
criteria 
1.3 Protocol Synopsis 
1.3 Protocol Synopsis 

 
 
 
 
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Clinical Trial Protocol Edition 1.0, 
dated 29-Apr-2021 
Previously written: 
Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Changed to: 
Exploratory Objectives page 11 
To assess SARS-CoV-2 specific peak 
humoral immune responses after the prime- 
boost regimen (Group 1) or the booster dose 
(Group 2) of the ABNCoV2 vaccine and 
compare these peak immune responses to 
those of subjects who had a previous SARS- 
CO-V-2 vaccination less than 3 months before 
SCR:. 
Exploratory Objectives page 11 
To assess SARS-CoV-2 specific peak 
humoral immune responses after the prime- 
boost regimen (Group 1) or the booster dose 
(Group 2) of the ABNCoV2 vaccine and 
compare these peak immune responses to 
those of subjects who had a previous SARS- 
CO-V-2 vaccination less than 3 months before 
SCR:. 
Exploratory objective adapted 
Trial Design page 12 
… In a run in phase 6 adults (comprising of 3 
subjects in each Group 1 and 2) will be 
vaccinated at 1 clinical trial site in a 
consecutive manner before opening up to full 
enrollment in Group 1 and 2. … 
 
The trial will begin with a run-in phase. This 
phase will include 6 adults (3 subjects in each 
of Groups 1 and 2, respectively) who will be 
vaccinated at 1 clinical trial site in a 
consecutive manner before opening the trial 
to full enrollment. 
Trial Design page 12 
…In a run in phase 6 adults (comprising of 3 
subjects in each Group 1 and 2) will be 
vaccinated at 1 clinical trial site in a 
consecutive manner, with an at least 48 
hours interval between the first and second 
subject of each group, then the second and 
third subject dosed on consecutive days, 
before opening up to full enrollment in 
Group 1 and 2… 
The trial will begin with a run-in phase. This 
phase will include 6 adults (3 subjects in each 
of Groups 1 and 2, respectively) who will be 
vaccinated at 1 clinical trial site in a 
consecutive manner (at least 48 hours 
between first and second subject in each 
group, and 1 subject per 1 day for second 
to third subject in each group) before 
opening the trial to full enrollment. 
Specified to address comments from PEI 

 
 
 
 
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Clinical Trial Protocol Edition 1.0, 
dated 29-Apr-2021 
Previously written: 
Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Changed to: 
Inclusion Criteria Page 13 
2. Seropositive (Group 2): Previous COVID-19 
disease or previous vaccination with an authorized 
SARS-CoV-2 vaccine at least 3 months before 
SCR, and a positive qualitative test for SARS- 
CoV-2 antibodies at SCR. 
6. Female subjects of childbearing potential 
(WOCBP) and male subjects who are sexually 
active with a WOCBP must agree to the use of an 
effective method of birth control from at least 
30 days prior to administration of the vaccine until 
30 days after the vaccination. 
 
 
 
 
 
15. Recent blood donation (including 
platelets, plasma and red blood cells) within 4 
weeks prior to SCR, or planned blood 
donations at any time during the trial. 
Inclusion Criteria Page 13 
2. Seropositive (Group 2): Previous COVID-19 
disease or previously completed vaccination 
regimen with an authorized SARS-CoV-2 vaccine 
at least 3 months before SCR, and a positive 
qualitative test for SARS-CoV-2 antibodies at 
SCR. 
6. Female subjects of childbearing potential 
(WOCBP) and male subjects who are sexually 
active with a WOCBP must agree to the use of an 
effective method of birth control from at least 
30 days prior to administration of the vaccine until 
30 days after the vaccination. Male subjects who 
are sexually active with a WOCBP must agree 
to the use of an effective method of birth 
control from the day of administration of the 
vaccine until 30 days after the vaccination. 
15. Recent blood donation (including 
platelets, plasma and red blood cells) within 4 
weeks prior to SCR, or planned blood 
donations at any time during the active trial 
phase. 
Adapted to address comments from PEI 
1.5 Responsibilities Page 
1.5 Responsibilities Page 
 
 
 
 
Office number replaced by mobile number 
4.1 Experimental Design 
4.1 Experimental Design 
 

 
 
 
 
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Clinical Trial Protocol Edition 1.0, 
dated 29-Apr-2021 
Previously written: 
Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Changed to: 
4.2.2 Active Trial Phase Page 28 
In total, 210 subjects will be enrolled in this trial. 
Recruitment will start with a run-in phase of 
6 subjects (3 in each of Groups 1 and 2, 
respectively, dosed on consecutive days) before 
opening up enrollment to both treatment groups. 
… 
 
 
 
After a positive DMC recommendation, 
enrollment of the rest of Groups 1 and 2 of the 
trial will commence. 
4.2.2 Active Trial Phase Page 28 
In total, 210 subjects will be enrolled in this trial. 
Recruitment will start with a run-in phase of 
6 subjects (3 in each of Groups 1 and 2, 
respectively, at least 48 hours interval between 
the first and second subject in each group, the 
second and third subject dosed on consecutive 
days) before opening up enrollment to both 
treatment groups. 
… 
After a positive DMC recommendation for each 
of the groups, enrollment of the rest of Groups 1 
and 2 of the trial will commence. 
Addressing PEI comments on dosing of 
consecutive days 
… The first 6 subjects (3 subjects each in Group 1 
and Group 2) will be vaccinated consecutively, at 
a maximum 1 per day. 
… The first 6 subjects (3 subjects each in Group 1 
and Group 2) will be vaccinated consecutively, at 
a maximum 1 per day. 
Deleted as specified in sections before 
4.4 Data Monitoring Committee 
4.4 Data Monitoring Committee 
The primary responsibility of the DMC is to 
review and evaluate the accumulated trial 
safety data after the run in phase and make 
recommendations to proceed to open 
enrollment for remaining subjects. If an event 
occurs which fulfills the trial halting rules (see 
Section 4.10 for further details) after the run 
in phase, the DMC will… 
The primary responsibility of the DMC is to 
review and evaluate the accumulated trial 
safety data after the run in phase and make 
recommendations to proceed to open 
enrollment for remaining subjects. If an event 
occurs which fulfills the trial halting rules (see 
Section 4.10 for further details) after the run 
in phase, the DMC will… 
Addressing PEI comments on dosing of 
consecutive days and DMC involvement 
9.1 Randomization Procedure 
9.1 Randomization Procedure 

 
 
 
 
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Clinical Trial Protocol Edition 1.0, 
dated 29-Apr-2021 
Previously written: 
Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Changed to: 
Subjects will be vaccinated in a consecutive 
manner (max 1 subject/day). 
Subjects will be vaccinated in a consecutive 
manner (max 1 subject/day) as described in 
Section 4.1 
Addressing PEI comments on dosing of 
consecutive days 
9.5 Analysis Population Page 50 
9.5 Analysis Population Page 50 
A blinded data review meeting will determine if 
any protocol violations will affect the 
immunogenicity outcomes and these subjects will 
be removed from the analysis set. 
A blinded data review meeting will determine if 
any protocol violations will affect the 
immunogenicity outcomes and these subjects will 
be removed from the analysis set. 
Typo removed 
 
9.7 Timing of Analysis page 
9.7.1 Primary Analysis 
9.7.2 Final Trial Analysis 
Chapter added to specify procedure of analysis 
e.g. addition of interim analysis 

 
 
 
 
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Appendix 6: Summary of Changes for Amendment #2 to the Clinical Trial 
Protocol 
 
 
An Open Label Phase 2 Trial to Evaluate the Safety, Tolerability and Immunogenicity of 
the ABNCoV2 Vaccine in SARS-CoV-2 Seronegative and Seropositive Adult Subjects 
Date of Edition 3.0: 15-Oct-2021 
 
 
Rationale 
The protocol Edition 3.0 has been created to implement the addition of a further treatment group 
of seropositive subjects (Group 3) receiving a dose of 50μg of IMP as well as adapting sample 
sizes of Group1 and 2. 
In addition, clarification of the inclusion and exclusion criteria were implemented, reflecting the 
current real-world experience in Germany, where many subjects have either mix&match 
regimens or a previous COVI-19 disease plus a single vaccine administration as reason for 
seropositivity. Due to the variety of reasons for seropositivity, stratification will therefore be now 
done based on baseline neutralizing antibody titer, instead of initial regimen. 
The new 50 μg dose group was selected based on preliminary results from the ongoing Phase 1 
first-in-human trial, indicating a dose saturation between 25μg and 70 μg dose groups, in terms of 
neutralizing antibody responses. For further details on Phase 1 data, please refer to the updated 
Investigator’s Brochure, Section 5. 
Changes 
Changes/ added terms are highlighted in bold letters in the text (table below), deleted terms are 
marked using strikethrough. 
Table 5 
Description 
 
Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Previously written: 
Clinical Trial Protocol Edition 3.0, 
dated 15-Oct-2021 
Changed to: 
1.1 Abbreviation 
1.1 Abbreviation 

 
 
 
 
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Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Previously written: 
Clinical Trial Protocol Edition 3.0, 
dated 15-Oct-2021 
Changed to: 
 
cVLP capsid virus-like particle 
added 
PBS 
Phosphate buffered saline 
1.2 Definitions 
1.2 Definitions 
Active Trial Phase: The period from the first 
vaccination up to and including 1 month (28- 
35 days) after receiving the last trial 
vaccination. For Group 1 this includes V1-V7. 
For Groups 2, this includes V1-V4. 
Active Trial Phase: The period from the first 
vaccination up to and including 1 month (28- 
35 days) after receiving the last trial 
vaccination. For Group 1 this includes V1- 
V7. For Groups 2 and 3, this includes V1- 
V4. 
Completed vaccination regimen …… 
“Completed” means administration of all 
vaccinations as described in the respective 
label. 
Completed vaccination regimen … 
“Completed” means administration of all 
vaccinations as described in the respective 
label includes full primary vaccination as 
described in the labeling of the initial 
vaccine, but also includes any mix/match 
series of 2 doses any authorized COVID-19 
vaccine. 
Last Vaccination: 
For Group 1 (seronegative) the last vaccination 
is the second vaccination of their two-dose 
prime-boost regimen, scheduled to be received 
at V4. For Groups 2 (seropositive) the last 
vaccination is the single boost vaccination 
received at V1. 
Last Vaccination: 
For Group 1 (seronegative) the last 
vaccination is the second vaccination of their 
two-dose prime-boost regimen, scheduled to 
be received at V4. For Groups 2 and 3 
(seropositive) the last vaccination is the 
single boost vaccination received at V1. 
1.3 Protocol Synopsis 
1.3 Protocol Synopsis 

 
 
 
 
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Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Previously written: 
Clinical Trial Protocol Edition 3.0, 
dated 15-Oct-2021 
Changed to: 
No of sites and countries 
1 to 3 sites, Germany and/or Netherlands 
 
Vaccination Dose and Schedule 
Each subject will receive either 2 doses of 100 
μg (Group 1), 1 dose of 100 μg (Group 2) 
ABNCoV2 vaccine. 
 
 
Trial Duration 
Approximately 104 weeks for initially 
seropositive subjects receiving 1 vaccination 
(Group 2). 
Sample Size 
A total of 210 healthy adult subjects will be 
enrolled into 2 groups: 
60 subjects determined to be seronegative for 
SARS-CoV-2 antibodies at screening (SCR) 
will be enrolled in Group 1. 
150 subjects determined to be seropositive for 
SARS-CoV-2 antibodies at SCR will be 
enrolled in Group 2. Enrollment will be 
stratified by reason for seropositivity, i.e., 
previous COVID-19 disease or type of 
previous vaccination received (mRNA vs. 
Adenovirus-based vaccination) such that at 
least 40 subjects and up to 70 subjects are 
enrolled in each stratification group (previous 
COVID-19 disease, previous mRNA 
vaccination or previous Adenovirus-based 
vaccination). 
No of sites and countries 
1 to 3 2 sites, Germany and/or Netherlands 
 
Vaccination Dose and Schedule 
Each subject will receive either 2 doses of 
100 μg (Group 1), 1 dose of 100 μg 
(Group 2) or 1 dose of 50 μg (Group 3) 
ABNCoV2 vaccine. 
 
Trial Duration 
Up tp 104 weeks for initially seropositive 
subjects receiving 1 vaccination (Group 2 and 
Group 3). 
Sample Size 
A total of 210 healthy adult subjects will be 
enrolled into 2 groups: 
Up to 30 subjects determined to be 
seronegative for SARS-CoV-2 antibodies at 
screening (SCR) will be enrolled in Group 1. 
Approx. 90 Up To 150 subjects determined to 
be seropositive for SARS-CoV-2 antibodies 
at SCR will be enrolled in Group 2 (100 μg). 
Enrollment will be stratified by reason for 
seropositivity, i.e., previous COVID-19 
disease or type of previous vaccination 
received (mRNA vs. Adenovirus-based 
vaccination) such that at least 40 subjects and 
up to 70 subjects are enrolled in each 
stratification group (previous COVID-19 
disease, previous mRNA vaccination or 
previous Adenovirus-based vaccination). 
Approx. 90 subjects determined to be 
seropositive for SARS-CoV-2 antibodies at 
SCR will be enrolled in Group 3 (50 μg). 

 
 
 
 
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Clinical Trial Protocol Edition 2.0, 
dated 1-Jul-2021 
Previously written: 
Clinical Trial Protocol Edition 3.0, 
dated 15-Oct-2021 
Changed to: 
Exploratory Endpoints 
Groups 2 (seropositive subjects): 
SARS-CoV-2 neutralizing antibody titers at 1 
week, 4 weeks, 3 months, 6 months, 1 year and 
2 years after vaccination. 
… 
Endpoints for each group will be analyzed 
separately. 
 
Groups 1 and 2 (all subjects): 
Cellular immune response, e.g., by Interferon-J
/ Interleukin-4 ELISPOT, at 1 week after the 
last vaccination, i.e., after the second 
vaccination in initially seronegative subjects 
and after the single boost vaccination in 
initially seropositive subjects. 
Exploratory Endpoints 
Groups 2 and 3 (seropositive subjects): 
SARS-CoV-2 neutralizing antibody titers at 1 
week, 4 weeks, 3 months, 6 months, 1 year 
and 2 years after vaccination. 
… 
Endpoints for each group will be analyzed 
separately. 
 
Groups 1, 2 and 3 (all subjects): 
Cellular immune response, e.g., by 
Interferon-J / Interleukin-4 ELISPOT, at 1 
week after the last vaccination, i.e., after the 
second vaccination in initially seronegative 
subjects and after the single boost vaccination 
in initially seropositive subjects. 
Trial Design 
Trial Design 

 
 
 
 
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A phase 1, dose ranging trial in healthy, 
seronegative adults is currently ongoing to 
evaluate safety and reactogenicity with doses 
up to 70μg 
 
In a run in phase 6 adults (comprising of 3 
subjects in each Group 1 and 2) … 
 
 
 
 
This phase 2 trial … compared to a single 
boost vaccination with 100 μg ABNCoV2 in 
initially seropositive subjects, …vaccination or 
previous COVID-19 disease (Group 2) at least 
3 months prior to enrollment (Table 1). 
 
 
Table 1 Treatment Groups and Number of 
Subjects 
Dose 
(/0.3 mL 
) 
Treatment Groups 
Tota 
l 
N 
Group 1 
Seronegativ 
e 
Group 2 
Seropositiv 
e 
100 μg 
60 subjectsa 
150 
subjectsa 
210 
N    = number of subjects 
a 
n = 3 of Group 1 and Group 2 (total 6 
subjects) will be enrolled in the run-in phase 
before opening the trial to full enrollment. 
 
 
 
For the seropositive subjects (Group 2), 
enrollment will be stratified by reason for 
seropositivity: previous COVID-19 disease, 
previous mRNA-based vaccination regimen, or 
previous Adenovirus-based vaccination 
regimen. Enrollment will occur in such a way 
A prior phase 1, dose ranging trial in healthy, 
seronegative adults is currently ongoing to 
evaluates safety and reactogenicity with 
doses up to 70μg 
 
For this Phase 2 trial, in a run in phase 6 
adults (comprising of 3 subjects in each 
Group 1 and 2) ......... Group 3 subjects will 
be enrolled after completion of Group 2 
enrollment. 
This phase 2 trial … compared to a single 
boost vaccination of 100 μg (Group 2) or 50 
μg (Group 3) of ABNCoV2 in initially 
seropositive subjects, … vaccination or 
previous COVID-19 disease at least 3 months 
90 days prior to enrollment (Table 1). 
 
Table 1 Treatment Groups and Number of 
Subjects 
Dose 
(/0.3 mL 
) 
Treatment 
Groups 
Total 
N 
Seronegativ 
e 
Seropositiv 
e 
 
100 μg 
Group 1 
30 
subjectsa 
Group 2 
90 
subjectsa 
12 
0 
50 μg 
 
Group 3 
90 subjects 
90 
Total 
210 
N    = number of subjects 
a 
n = 3 of Group 1 and Group 2 (total 6 
subjects) will be enrolled in the run-in phase 
before opening the trial to full enrollment. 
For the seropositive subjects (Groups 2 and 
3), enrollment will be stratified by reason for 
the reason for seropositivity will be 
documented (previous COVID-19 disease, 
previous mRNA-based vaccination regimen, 

 
 
 
 
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that at least 40 and up to 70 subjects will be 
included in each stratification group. 
 
 
 
 
 
 
The trial will begin with a run-in phase. … 
… After a positive DMC recommendation, 
enrollment of the rest of Groups 1 and 2 of the 
trial will commence. 
or previous Adenovirus-based vaccination 
regimen). 
Enrollment will occur in such a way that at 
least 40 and up to 70 subjects will be 
included in each stratification group. 
Due to the timing of the addition of Group 
3, enrollment into Group 2 will be 
completed prior to enrolling subjects into 
Group 3. Therefore, no randomization 
will be required for the seropositive 
subjects. 
The trial will begin with a run-in phase. … 
After a positive DMC recommendation, 
enrollment of the rest of Groups 1 and 2 of 
the trial will commence. 
Inclusion Criteria 
Inclusion Criteria 
#2 …Seropositive (Group 2): Previous 
COVID-19 disease or previously completed 
vaccination regimen with an authorized SARS- 
CoV-2 vaccine at least 3 months before SCR, 
and a positive qualitative test for SARS-CoV-2 
antibodies at SCR. … 
#2: …Seropositive (Group 2 and Group 3): 
Previous COVID-19 disease or previously 
completed vaccination regimen with an 
authorized SARS-CoV-2 vaccine at least 90 
days before SCR planned trial vaccination, 
and a positive qualitative test for SARS-CoV- 
2 antibodies at SCR. 
…Receipt of a single dose of an authorized 
COVID-19 vaccine regimen in subjects 
with a previous diagnosis of COVID-19 or 
a mix/match series of 2 doses of any 
authorized COVID-19 vaccine will be 
considered as a completed vaccination. 
Exclusion Criteria 
Exclusion Criteria 
 
#1 Groups 2 and 3 only: History of 
COVID-19 infection and subsequent 
receipt of more than one licensed or 
candidate SARS-CoV-2 vaccine. 
1.5 Responsibilities 
1.5 Responsibilities 

 
 
 
 
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Trial Schedule 
Trial Schedule 
AE/SAE/AESI recording 
AE/SAE/AESI recording starting at 
screening visit 
AESIs are not collected until vaccine has 
been received at visit 1. 
2.4 Clinical Trial Data with ABNCoV2 
Vaccine 
2.4 Clinical Trial Data with ABNCoV2 
Vaccine 
Preliminary safety results in 18 subjects dosed 
up to 25 μg did not show any relevant safety 
findings. No final results from this trial are 
available yet. For further dose justification, 
please refer to Section 2.3 
Preliminary safety results in 45 subjects 
dosed up to 70 μg did not show any relevant 
safety findings. No final results from this trial 
are available yet. For further dose 
justification, please refer to Section 2.3 
2.5 Rationale 
2.5 Rationale 
This trial will, therefore, evaluate both an 
initial two-dose vaccination regimen of 
ABNCoV2 in seronegative subjects as well as 
a single dose boost regimens of ABNCoV2 in 
seropositive subjects. 
This trial will, therefore, evaluate both an 
initial two-dose vaccination regimen of 
ABNCoV2 in seronegative subjects as well 
as a two single dose boost regimens of 
ABNCoV2 in seropositive subjects. 
2.7.1 Potential Risk 
2.7.1 Potential Risk 

 
 
 
 
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As with all vaccines, … site pain, erythema, 
swelling, pruritus or induration, as well as 
systemic inflammatory reactions including 
unspecific flu-like symptoms such as fever, 
headache, nausea, muscle pain, chills or 
fatigue. 
Based on available data from COUGH-1 
study, there have been no SAEs reported. 
As with all vaccines, …site pain and/or 
tenderness, erythema, swelling, pruritus or 
induration. The above mentioned were 
reported most commonly in the COUGH-1 
study following both doses of study 
vaccine. Also, systemic inflammatory 
reactions including flu-like symptoms such as 
fever, headache, nausea, muscle pain, chills 
or fatigue can occur. Headache, chills and 
fatigue were reported most commonly in 
the COUGH-1 study after first dose of 
study vaccine. After the second dose of 
study vaccine, myalgia was mostly 
commonly reported, followed by nausea, 
hyperhidrosis and a general feeling of 
warmth without fever. 
4.1 Experimental Design 
4.1 Experimental Design 
The trial will evaluate a homologous prime- 
boost regimen with 100 μg ABNCoV2 in … 
single boost vaccination with 100 μg 
ABNCoV2 in initially seropositive subjects 
(Group 2), as defined by a positive qualitative 
test for SARS-CoV-2 antibodies and a history 
of SARS-CoV-2 vaccination or previous 
COVID-19 disease at least 3 months prior to 
enrollment (Table 1). 
The trial will evaluate a homologous prime- 
boost regimen with 100 μg ABNCoV2 in … 
single boost vaccination with either 100 μg 
or 50 μg dose of ABNCoV2 in initially 
seropositive subjects (Groups 2 and 3), as 
defined by a positive qualitative test for 
SARS-CoV-2 antibodies and a history of 
SARS-CoV-2 vaccination or previous 
COVID-19 disease at least 90 days prior to 
enrollment (Table 1). 
… 
Due to the timing of the addition of Group 
3, enrollment into Group 2 will be 
completed prior to enrolling subjects into 
Group 3. Therefore, no randomization 
will be required for the seropositive 
subjects. 

 
 
 
 
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2.7.1 Potential Risk 
2.7.1 Potential Risk 
 
 
As with all vaccines, there is a risk of an 
allergic reaction or an anaphylactic event. Trial 
site staff will observe subjects for at least 
30 minutes after each vaccination and, in the 
event that a severe allergic reaction and/or 
dyspnoea might occur, appropriate medical 
treatment and supervision will be readily 
available. 
As with all vaccines, there is also a risk of 
temporary mild to moderate injection site 
reactions, such as injection site pain, erythema, 
swelling, pruritus or induration, as well as 
systemic inflammatory reactions including 
unspecific flu-like symptoms such as fever, 
headache, nausea, muscle pain, chills or 
fatigue 
Based on available data from COUGH-1 
study, there have been no SAEs reported. 
As with all vaccines, there is a risk of 
temporary mild to moderate injection site 
reactions, such as injection site pain and/or 
tenderness, erythema, swelling, pruritus or 
induration. The above mentioned were 
reported most commonly in the COUGH-1 
study following both doses of study 
vaccine. Also, systemic inflammatory 
reactions including flu-like symptoms such as 
fever, headache, nausea, muscle pain, chills 
or fatigue can occur. 
Headache, chills and fatigue were reported 
most commonly in the COUGH-1 study after 
first dose of study vaccine. After the second 
dose of study vaccine, myalgia was mostly 
commonly reported, followed by nausea, 
hyperhidrosis and a general feeling of 
warmth without fever 
4.1 Experimental Design 
4.1 Experimental Design 

 
 
 
 
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…with 100 μg ABNCoV2 in initially 
seropositive subjects (Group 2), as defined by 
a positive qualitative test for SARS-CoV-2 
antibodies and a history of SARS-CoV-2 
vaccination or previous COVID-19 disease at 
least 3 months prior to enrollment 
…In total, 210 subjects will be enrolled in this 
trial. 
… with either 100 μg or 50 μg dose of 
ABNCoV2 in initially seropositive subjects 
(Groups 2 and 3), as defined by a positive 
qualitative test for SARS-CoV-2 antibodies 
and a history of SARS-CoV-2 vaccination or 
previous COVID-19 disease at least 3 months 
90 days prior to enrollment 
…In total, approximately 210 subjects will 
be enrolled in this trial. 
Due to the timing of the addition of Group 
3, enrollment into Group 2 will be 
completed prior to enrolling subjects into 
Group 3. Therefore, no randomization will 
be required for the seropositive subjects. 
4.2.2 Active Trial Phase 
4.2.2 Active Trial Phase 
At V1/Day 1 each subject in Groups 1 and 2 
will receive 1 dose of 100 μg ABNCoV2 
vaccine administered IM into the deltoid 
muscle of the upper arm (preferably the non- 
dominant arm). 
… 
For Group 1, the memory aid will be collected 
for the 8-day period for both vaccinations. 
At V1/Day 1 each subject in Groups 1 and 2 
will receive 1 dose of 100 μg ABNCoV2 
vaccine, and Group 3 will receive 1 dose of 
50 μg ABNCoV2 vaccine administered IM 
into the deltoid muscle of the upper arm 
(preferably the non-dominant arm). 
… 
For each subject in Group 1, two memory 
aids will be collected for the 8-day period 
(one for each of the two vaccinations). 
4.2.5 Early Discontinuation 
4.2.5 Early Discontinuation 
 
Subject’s receipt of an approved booster 
vaccination for SARS-CoV-2. 

 
 
 
 
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6.1 Production, Packaging and Labelling 
6.1 Production, Packaging and Labelling 
 
For dilution buffer phosphate buffered 
saline (PBS) is used and released by 
Bavarian-Nordic A/S, DK. The packages 
and vials of dilution buffer are labeled 
according to regulatory requirements. 
6.2. Shipment, Storage and Handling 
6.2. Shipment, Storage and Handling 
Details on shipment, storage and handling of 
the IMP are provided in the pharmacy manual. 
Details on shipment, storage and handling of 
the IMP (and comparable information for 
the diluent to be used for Group 3) are 
provided in the pharmacy manual. 
7.3 Future Use of Lab Specimen 
7.3 Future Use of Lab Specimen 
… data collected from subjects vaccinated 
with competitor vaccines. Further, remaining 
samples might be used for assay development 
and controls. Subjects will be asked to consent 
to storage/future use of samples and will be 
informed about data protection measures. 
data collected from subjects vaccinated with 
competitor other COVID-19 vaccines. 
Further, remaining samples might be used for 
assay development and controls. Subjects 
will be invited to consent to storage/future 
use of samples and will be informed about 
data protection measures. 
8.1.2.3 AEs and SAEs 
8.1.2.3 AEs and SAEs 
AESIs are reportable by the clinical 
investigators as per SAE protocol provisions. 
AESIs are reportable by the clinical 
investigators as per SAE protocol provisions. 
All AEs are collected from signing of ICF, 
however should not be considered by 
investigator to be an AESI unless 
occurring since receipt of first vaccination. 

 
 
 
 
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8.1.3 Relevant Medical History 
8.1.3 Relevant Medical History 
 
In particular, subjects with prior COVID- 
19 infection need to include the infection 
and dates in the medical history section of 
the eCRF. 
8.1.4 Prior and Concomitant Medication 
8.1.4 Prior and Concomitant Medication 
 
In addition, subjects with previous SARS- 
CoV-2 vaccination will include the specific 
vaccine received by dose and date in the 
eCRF, regardless of the time elapsed prior to 
SCR. 
8.1.5 Prohibited Medication 
8.1.5 Prohibited Medication 
 
In case official guidelines require booster 
vaccinations to maintain valid COVID-19 
vaccination certificates, approved booster 
vaccinations for SARS-CoV-2 are allowed 
for Groups 2 and 3 within the follow-up 
period, however subjects will be 
withdrawn from further follow up. 
8.1.11 Cardiac Assessment 
8.1.11 Cardiac Assessment 

 
 
 
 
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A standard 12-lead ECG will be taken at the 
SCR. At any other visit an ECG is only 
performed if clinically indicated. For unclear 
ECGs the investigator can obtain ECG over- 
read by a local cardiologist. All further 
clinically indicated ECGs will be rated by a 
cardiologist who would also receive the 
baseline ECG for review. The workflow 
communication will be provided in a separate 
manual. 
8.2.1 Reporting of SAE and AESIs 
8.2.1 Reporting of SAE and AESIs 
All SAEs and AESIs occurring throughout the 
entire course of the trial … 
All SAEs (collection starts at signing of 
ICF) and AESIs (collection starts upon 
receiving first vaccination) occurring 
throughout the entire course of the trial … 
8.2.2 Reporting of Pregnancies 
8.2.2 Reporting of Pregnancies 
… must be on the Pregnancy Notification 
Report Form within 24 hours ... 
A pregnancy will be followed to term, ...on a 
Pregnancy Outcome Report Form. 
... must be recorded on the Pregnancy 
eCRF (or Pregnancy Notification Report 
Form if EDC unavailable) within 24 hours 
... 
A pregnancy will be followed to term, ...by 
recording outcome on the pregnancy eCRF 
(or Pregnancy Outcome Report Form if 
EDC unavailable). 
9.1 Randomization Procedure 
9.1 Randomization Procedure 

 
 
 
 
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After completion of V2 and positive review of 
safety data by the DMC, the DMC will allow 
for the enrollment of all remaining subjects in 
both treatment groups. Assignment into 
Group 1 versus Group 2 will be based on the 
subjects’ baseline SARS-CoV-2 antibody 
status. Group 2 will be stratified by 
seropositive category: previous COVID-19 
infection, mRNA vaccinated, or adenovirus- 
vaccinated. 
After completion of V2 and positive review 
of safety data by the DMC, the DMC will 
allow for the enrollment of all remaining 
subjects in both treatment groups. 
Assignment into Group 1 versus Group 2 and 
3 will be based on the subjects’ baseline 
SARS-CoV-2 antibody status. For 
seropositive subjects the reason for 
seropositivity will be documented: previous 
COVID-19 infection, mRNA vaccinated, 
adenovirus-vaccinated, or a mix of those. 
Due to the timing of the addition of Group 
3, enrollment into Group 2 will be 
completed prior to enrolling subjects into 
Group 3. Therefore, no randomization 
will be required for the seropositive 
subjects. 
9.2 Sample Size Calculation 
9.2 Sample Size Calculation 
 
Whole chapter was adapted to reflect 
addition of Group 3 and adapting size of 
different treatment groups 
9.6.1.3 Primary Analysis 
9.6.1.3 Primary Analysis 

 
 
 
 
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For Groups 2 and 3, analyses of fold- 
increases will be performed by baseline 
titer catetories (median or median) to 
account for the expected variation in the 
baseline neutralizing titer due to the 
different reasons for seropositivity (i.e., 
previous mRNA vaccination, previous 
Adenovirus-based vaccination, or previous 
COVID-19 infection). As the Groups 2 
and 3 baseline titer distributions are 
assumed to be the same, the median 
baseline neutralizing titer category will be 
derived from the median of both groups. 
This will allow for comparability between 
the geometric fold-increases by dose level 
(i.e., 100 μg vs. 50 μg). 
9.6.3 Exploratory Endpoints 
9.6.3 Exploratory Endpoints 
These data will be summarized descriptively 
by geometric means and 95% confidence 
intervals for each time point and each group 
(Group 1 and Group 2). 
 
 
Response rates, ... having an at least 2-fold 
increase or 4-fold increase from baseline in 
Groups 2 and 3, respectively, will also be 
summarized by time points and groups, … 
These data will be summarized descriptively 
by geometric means and 95% confidence 
intervals for each time point within each of 
the three groups. For Groups 2 and 3, 
analyses will be performed by the baseline 
neutralizing titer category (<median or 
median). 
Response rates, ... having an at least 2-fold 
increase or 4-fold increase from baseline in 
Groups 2 and 3, respectively, will also be 
summarized by time points and groups...