A Non-Randomized, Open Label, Controlled, Dose-Escalation, Phase I Clinical Trial to Evaluate the Safety, Reactogenicity and Immunogenicity of One or Two Administrations of Candidate Rabies mRNA Vaccine CV7202 in Healthy Adult Subjects
Phase: PHASE1
Conditions: Rabies
Sponsor: CureVac

Clinical Trial Protocol 
CV-7202-104 
CureVac AG 
 
 
V2.0 (30 April 2020) 
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CLINICAL TRIAL PROTOCOL 
A non-randomized, open label, controlled, dose-escalation, phase I clinical trial 
to evaluate the safety, reactogenicity and immunogenicity of one or two 
administrations of candidate rabies mRNA vaccine CV7202 in healthy adult 
subjects 
Protocol Number: 
CV-7202-104 
EudraCT Number: 
2017-002856-10 
Investigational medicinal 
product: 
CV7202 
Phase: 
Phase I 
Sponsor: 
CureVac AG 
Schumannstr. 27 
D-60325 Frankfurt 
Germany 
Short Title: 
Safety, reactogenicity and immunogenicity of 
CV7202 in healthy adult subjects 
Protocol Date: 
30 April 2020 
Protocol Version: 
2.0 
Version History 
N/A 
This protocol may not be reproduced or communicated to a third party without the 
written permission of CureVac AG 

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APPROVAL SIGNATURES 
Protocol Title: 
A non-randomized, open label, controlled, dose-escalation, 
phase I clinical trial to evaluate the safety, reactogenicity and 
immunogenicity of one or two administrations of candidate 
rabies mRNA vaccine CV7202 in healthy adult subjects 
Protocol Number: 
CV-7202-104 
This trial will be conducted with the highest respect for the individual subjects in 
compliance with the requirements of this clinical trial protocol (and amendments), 
and also in compliance with the following: 
 The ethical principles that have their origin in the Declaration of Helsinki. 
 International Council for Harmonisation of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) E6 (R2) Good Clinical Practice 
(GCP): Revised and consolidated guidelines [1]. 
 All applicable laws and regulations, including, without limitation, data 
privacy laws, clinical trial disclosure laws, and regulations. 
Sponsor Signatory 
Signature 
Date  
 

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SAE Hotline 
SAE reporting to 
by fax or email within 24 hours after discovery: 
Europe 
SAE Fax-no.: 
Email: 
Address: 

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Table of contents 
1 
Synopsis .............................................................................................................. 8 
2 
Schedule of Activities ......................................................................................... 14 
3 
Introduction ........................................................................................................ 17 
3.1 
RNActive® technology ................................................................................. 17 
4 
Objectives and Endpoints .................................................................................. 19 
4.1 
Objectives .................................................................................................... 19 
4.2 
Endpoints .................................................................................................... 20 
5 
Trial Design ........................................................................................................ 23 
5.1 
Overall Design ............................................................................................. 23 
5.1.1 Dose-finding Schedule, Enrolment Plan ............................................... 23 
5.1.2 Stopping Rules ...................................................................................... 24 
5.1.3 Timing of Blood Collection for Safety and Immunogenicity Parameters 25 
5.2 
Subject and Trial Completion ...................................................................... 26 
5.3 
End of Trial Definition .................................................................................. 26 
5.4 
Trial Data Review ........................................................................................ 26 
5.5 
Data and Safety Monitoring Board .............................................................. 26 
5.6 
Scientific Rationale for Trial Design ............................................................. 26 
5.7 
Justification for Dose ................................................................................... 27 
5.8 
Benefit-Risk Assessment ............................................................................. 27 
5.8.1 Possible Risks and Adverse IMP Reactions ......................................... 27 
5.8.2 Adverse Events of Special Interest ....................................................... 28 
5.8.3 Drug and Vaccines Interactions ............................................................ 28 
5.8.4 Precautions and Warnings .................................................................... 29 
5.8.5 Recognition and Treatment of Possible Overdose and Adverse IMP 
Reactions ......................................................................................................... 29 
5.8.6 Benefit-Risk Conclusion ........................................................................ 29 
6 
Trial Population .................................................................................................. 30 
6.1 
Inclusion Criteria .......................................................................................... 30 
6.2 
Exclusion Criteria......................................................................................... 31 
6.3 
Dose Modification / Vaccine Delay Recommendations ............................... 32 
6.4 
Screen Failures ........................................................................................... 32 
7 
Discontinuation/Withdrawal Criteria ................................................................... 33 
7.1 
Discontinuation of Trial Vaccine Administration and/or Blood Sampling ...... 33 
7.2 
Withdrawal from the Trial ............................................................................. 34 
7.3 
Trial Termination.......................................................................................... 34 
7.4 
Lost to Follow-Up......................................................................................... 35 
8 
Clinical Trial Material Management .................................................................... 36 
8.1 
Trial Vaccine and Formulation ..................................................................... 36 
8.2 
Control Vaccine ........................................................................................... 36 
8.3 
Route of Administration ............................................................................... 36 
8.4 
Trial Groups ................................................................................................. 36 
8.5 
Method of Trial Vaccine Assignment ........................................................... 37 
8.6 
Blinding ........................................................................................................ 37 
8.7 
Trial Vaccine and Supplies Accountability ................................................... 37 
8.8 
Vaccine Compliance .................................................................................... 37 
8.9 
Concomitant Therapy and Vaccines ............................................................ 38 
8.10 Therapy leading to elimination ..................................................................... 38 
8.11 Treatment after the End of the Trial ............................................................. 38 

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9 
Trial Assessments and Procedures ................................................................... 39 
9.1 
Adverse Events ........................................................................................... 39 
9.2 
Safety Assessments .................................................................................... 41 
9.3 
Immunogenicity Assessments ..................................................................... 42 
9.4 
Trial Procedures .......................................................................................... 43 
9.4.1 Visit 1 (Pre-screening Visit, Days -90 to -1) .......................................... 43 
9.4.2 Visit 2 (Screening Visit, Days -30 to -1) ................................................ 43 
9.4.3 Visit 3 (Vaccination Dose 1 CV7202 or Dose 1 Rabipur®, Day 1) ......... 44 
9.4.4 Visit 4 (Day 2 or 3) ................................................................................ 44 
9.4.5 Phone call (Day 3) ................................................................................ 45 
9.4.6 Visit 5 (Vaccination Dose 2 Rabipur®, Day 8) ....................................... 45 
9.4.7 Visit 6 (Day 10) ..................................................................................... 46 
9.4.8 Visit 7 (Day 15) ..................................................................................... 46 
9.4.9 Visit 8 (Vaccination Dose 2 CV7202* or Dose 3 Rabipur®, Day 29) ...... 47 
9.4.10 Visit 9 (Day 30 or 31**) ......................................................................... 47 
9.4.11 Phone call (Day 31) .............................................................................. 48 
9.4.12 Visit 10 (Day 36) ................................................................................... 48 
9.4.13 Visit 11 (Day 43) ................................................................................... 49 
9.4.14 Visit 12 (Day 57) ................................................................................... 49 
9.4.15 Visit 13 (Day 91) ................................................................................... 49 
9.4.16 Visit 14 (Month 6: Day 181 [1-dose groups]/ Day 209 [2-dose groups and 
Group 1 (Rabipur®)] ......................................................................................... 50 
9.4.16.1 
Visit 14 .....................................................................................................50 
9.4.16.2 
Optional Visit 14A .....................................................................................50 
9.4.17 Visit 15 (Month 12: Day 365 [1-dose groups]/ Day 393 [2-dose groups 
and Group 1 (Rabipur®)]................................................................................... 50 
9.4.17.1 
Visit 15 .....................................................................................................50 
9.4.17.2 
Optional Visit 15A .....................................................................................51 
9.4.18 Visit 16 (Month 18: Day 547)................................................................. 51 
9.4.18.1 
Visit 16 .....................................................................................................51 
9.4.18.2 
Optional Visit 16A .....................................................................................51 
9.4.19 Visit 17 (Trial End) (Month 24: Day 729) ............................................... 52 
9.4.19.1 
Visit 17 .....................................................................................................52 
9.4.19.2 
Optional Visit 17A .....................................................................................52 
9.5 
Blood Draws ................................................................................................ 53 
9.5.1 Safety Lab (Visits 2 to 5, 7 to 10 and 12 to 15) ..................................... 55 
9.5.2 Thyroid-stimulating Hormone, Thyroid Antibodies, Antinuclear Antibodies 
(Pre-screening Visit) ......................................................................................... 55 
9.5.3 Immunogenicity (Visits 3 to 5, 7 to 17) .................................................. 55 
10 Statistical Considerations ................................................................................... 57 
10.1 Sample Size Determination ......................................................................... 57 
10.2 Populations for Analyses ............................................................................. 57 
10.3 Statistical Analyses...................................................................................... 58 
10.3.1 General Considerations ........................................................................ 58 
10.3.2 Demographic, Medical History, Prior Medication and other Baseline 
Characteristics ................................................................................................. 58 
10.3.3 Study vaccine........................................................................................ 58 
10.3.4 Concomitant medication and Vaccinations ........................................... 58 
10.3.5 Safety Analyses .................................................................................... 58 

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10.3.6 Immunogenicity Analyses (Secondary/Exploratory Objectives) ............ 59 
10.3.7 Missing data .......................................................................................... 59 
10.3.8 Interim analyses .................................................................................... 60 
11 References ......................................................................................................... 61 
12 Appendices ........................................................................................................ 64 
 

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List of Appendices 
Appendix 1 
Investigator Signature Page ............................................................... 65 
Appendix 2 
Responsibilities of the Investigator ..................................................... 67 
Appendix 3 
Protocol Approvers............................................................................. 69 
Appendix 4 
Emergency Procedures ...................................................................... 70 
Appendix 5 
Abbreviations and Trademarks .......................................................... 71 
Appendix 6 
Clinical Laboratory Tests .................................................................... 73 
Appendix 7 
Trial Governance Considerations ....................................................... 74 
Appendix 8 
Protocol changes ............................................................................... 76 
Appendix 9 
Disclosure .......................................................................................... 77 
Appendix 10 Adverse Events of Special Interest .................................................... 78 
Appendix 11 Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ................................................ 80 
Appendix 12 Contraceptive Guidance and Collection of Pregnancy Information .... 86 
Appendix 13 Data Management and Quality Control .............................................. 88 
Appendix 14 Protocol Deviations ............................................................................ 90 
Appendix 15 Ethics and Regulations ...................................................................... 91 
Appendix 16 Biological Samples and Record Retention ......................................... 92 
Appendix 17 Protocol Amendment History ............................................................. 93 
 
List of Tables 
Table 2.1 
Schedule of Activities ......................................................................... 14 
Table 2.2 
Staggered Enrolment and Dose Escalation for Groups 2 to 4 
(Dose 1) with Minimum Time Intervals* .............................................. 16 
Table 8.1 
Protocol CV-7202-104 Dose regimen ................................................ 37 
Table 9.1 
Intensity Grading for Solicited Local AEs (Days 1 to 8) ...................... 39 
Table 9.2 
Intensity Grading* for Solicited Systemic AEs (Days 1 to 8) .............. 40 
Table 9.3 
Timing and Maximum Volumes of Blood Draws ................................. 54 
Table 12.1 
Protocol-Required Safety Laboratory Assessments ........................... 73 
Table 12.2 
List of Names and Addresses ............................................................ 74 
 
List of Figures 
Figure 5.1 
CV-7202-104 Trial Design .................................................................. 23 
 

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1 Synopsis 
Protocol 
Title: 
A non-randomized, open label, controlled, dose-escalation, phase I clinical 
trial to evaluate the safety, reactogenicity and immunogenicity of one or two 
administrations of candidate rabies mRNA vaccine CV7202 in healthy adult 
subjects 
Short Title: 
Safety, reactogenicity and immunogenicity of CV7202 in healthy adult 
subjects 
Rationale: 
The objectives of this phase I trial are to assess the safety and 
reactogenicity of CV7202 in the context of immune responses to rabies virus 
glycoprotein (RABV-G) in order to select the optimal dose and number of 
doses. The dose range selected is intended to provide data for defining the 
optimal dosage of CV7202 to be tested in subsequent clinical trials. 
Sponsor: 
CureVac AG 
Schumannstr. 27 
D-60325 Frankfurt 
Germany 
Coordinating/ 
Principal 
Investigator: 
Trial Objectives and Endpoints: 
Objectives 
Endpoints 
Primary 
 
 
To assess the safety and reactogenicity 
profile of CV7202 administered 
intramuscularly (i.m.) to healthy adults 
(18–40 years old), as a range of doses 
(1, 2 and 5 µg) in one- or two-dose 
regimens. 
 
The percentages of subjects with, and the 
frequencies and intensities of solicited 
local adverse events (AEs) reported on 
the day of vaccination and the 7 
subsequent days (Days 1-8). 
 
 
The percentages of subjects with, and the 
frequencies, intensities and relationship to 
vaccination, of solicited systemic AEs 
reported on the day of vaccination and the 
7 subsequent days (Days 1-8). 
 
 
The duration (in days) of solicited local 
AEs, of solicited systemic AEs and of the 
individual solicited AEs. 

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 
The percentages of subjects with and 
frequencies and intensities of any 
unsolicited and related unsolicited AEs 
reported on the day of vaccination and the 
28 subsequent days (Days 1-29). 
 
 
The percentages of subjects with and 
frequencies and relationship to 
vaccination of any serious adverse events 
(SAEs) and any medically-attended AEs 
(MAAEs) up to 12 months post last dose. 
 
 
The percentages of subjects with and 
frequencies and relationship to 
vaccination of any adverse events of 
special interest (AESIs) up to 12 months 
post vaccination. 
Secondary 
 
For safety: 
 
To assess the safety profile of CV7202 
administered i.m. to healthy adults (18-40 
years old), as a range of doses (1, 2 and 
5 µg) in one- or two-dose regimens in the 
period from 12 to 24 months post last 
dose. 
 
The percentages of subjects with and 
frequencies of SAEs and MAAEs related 
to study vaccination from 12 months post 
last dose up to 24 months post last dose 
(trial end). 
 
 
The percentages of subjects with and 
frequencies and relationship to 
vaccination of any AESIs from 12 months 
post last dose up to 24 months post last 
dose (trial end). 
For the characterization of the humoral immune response: 
 
To evaluate the potential protective 
immune responses to CV7202 and 
Rabipur® in healthy adults (18–40 years 
old), by assessing the percentages of 
subjects with rabies-specific serum virus-
neutralizing antibody titers (VNTs) 
≥0.5 IU/ml. 
 
Percentages of subjects with rabies-
specific serum VNTs ≥0.5 IU/ml by trial 
group on Days 1 (pre-vaccination), 15, 43, 
and 12, 18* and 24* months post last 
dose. 
* Will be performed only in subjects with 
detectable RABV-G-specific IgG at 6 months 
after the last vaccination or Day 91 if the 
Month 6 blood sample is not available.  

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 
To evaluate the immunogenicity (VNTs) 
of CV7202 administered to healthy adults 
(18–40 years old), as a range of doses 
(1, 2 and 5 µg) in one- or two-dose 
regimens and the immunogenicity of 
Rabipur® administered in a 3-dose 
regimen. 
 
Serum geometric mean titers (GMTs) of 
virus-neutralizing antibodies by trial group 
on Days 1, 8, 15, 29, 36, 43, 57, 91, and 
6, 12, 18* and 24* months post-last dose.  
* Will be performed only in subjects with 
detectable RABV-G-specific IgG at 6 months 
after the last vaccination or Day 91 if the 
Month 6 blood sample is not available. 
Exploratory 
 
For the evaluation of the innate immune response: 
 
To evaluate the innate immune response 
to one or two doses of CV7202 compared 
with baseline. 
 
Serum cytokine concentrations*, including 
but not limited to CXCL10, CCL3, IL-6, 
TNF-α and IFN-γ, at pre-vaccination and 
4 hours post-vaccination on Day 1, and 
Days 2 or 3** and 8 after each 
vaccination.  
 
 
Transcriptome profiling* on the day of 
vaccination at pre-vaccination, and Days 
2 or 3** and 8 after each vaccination. 
* Will be performed in the first 5 subjects in 
Group 2 (** on Day 3) and all subjects in 
Groups 3 and 4 (** on Day 2). Note that Day 
3 was planned in the original protocol and 
only applies to subjects in Group 2 who were 
already enrolled and vaccinated before this 
protocol amendment was issued. Day 2 
applies to all other subjects. 
For the evaluation of antigen specific T-cell response: 
 
To evaluate the frequencies and 
functionalities of RABV-G-specific T cells 
after one or two doses of CV7202 
compared with baseline. 
 
The frequencies and functionalities of 
RABV-G-specific T cells in peripheral 
blood from the first 5 subjects in Group 2 
and all subjects in Groups 3 and 4 on 
Days 1, 8, 36, 91*, and 6* and 12* months 
post-last dose. 
* For groups that have shown a significant T-
cell response at Day 8 or 36 compared to 
baseline. 
For the evaluation and characterization of the B-cell response: 
 
To evaluate the frequencies of RABV-G-
specific B cells after one or two doses of 
CV7202 compared with baseline. 
 
The frequencies of RABV-G-specific B 
cells in peripheral blood from the first 5 
subjects in Group 2 and all subjects in 
Groups 3 and 4 on Days 1, 8, 36, 91*, and 
6* and 12* months post-last dose. 

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 
To evaluate the effect of vaccination on 
B-cell phenotype and activation after one 
or two doses of CV7202 compared with 
baseline. 
 
The frequencies and activation status of 
phenotypically distinct subsets of B cell 
populations, including but not limited to 
naïve and memory B cells, plasmablasts 
and plasma cells for the first 5 subjects in 
Group 2 and all subjects in Groups 3 and 
4 on Days 1, 8, 36, 91*, and 6* and 12* 
months post-last dose. 
 
To evaluate the effect of vaccination on 
B-cell clonality after one or two doses of 
CV7202 compared with baseline. 
 
Sequencing of B-cell receptors (BCR) of 
circulating B cells on Days 1, 8, 29, 36, 
57, 91*, and 6* and 12* months post-last 
dose. 
* For groups that have shown a significant B-
cell response at Day 8 or 36 compared to 
baseline. 
For the characterization of the humoral immune response: 
 
To evaluate RABV-G-specific antibody 
responses throughout the trial including 
the follow-up period by assessing IgM, 
IgG and IgA levels. 
 
RABV-G-specific IgM, IgG and IgA levels 
measured by ELISA on Days 1, 8, 15, 29, 
36, 43, 57, 91, and 6 and 12 months post-
last dose. 
 
RABV-G-specific IgG levels measured by 
ELISA 18* and 24* months post-last dose. 
* Will be performed only in subjects with 
detectable RABV-G-specific IgG at 6 months 
after the last vaccination or Day 91 if the 
Month 6 blood sample is not available.  
 
To characterize the nature and quality of 
the RABV-G-specific antibody response, 
by measuring the serum affinity and 
avidity after one or two doses of CV7202 
and the breadth of neutralization against 
heterologous lyssaviruses with variant 
epitopes. 
 
Identification of epitopes recognized by 
vaccine-induced antibodies on Days 1, 
15, 43, and 12 months post last dose*. 
 
Measurement of RABV-G-specific 
antibody avidity and affinity on Days 1, 15, 
43, and 12 months post last dose*. 
 
Measurement of VNTs against additional 
heterologous lyssaviruses on Days 1, 15, 
43, and 12 months post last dose*. 
* Will be performed only on selected samples 
with VNT >0.5 IU/ml. 
Overall Design: 
This is a non-randomized, open label, controlled, dose-escalation, 
phase I clinical trial to evaluate the safety, reactogenicity and 
immunogenicity of one or two i.m. administrations of candidate rabies 
mRNA vaccine CV7202 in healthy adult subjects. The subjects will be 
enrolled sequentially in up to 4 trial groups to receive either a dose of 
CV7202 containing different mRNA content or Rabipur®. In a first 
CV7202 group, 10 subjects have received a dose containing 5 µg 
mRNA. A dose of 1 or 2 µg mRNA will be administered to 2 additional 

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groups of 16 subjects each, of whom 8 in each group will be 
administered a second dose 28 days later.  
A control group of 10 subjects will receive 3 doses of the licensed 
vaccine Rabipur® according to the manufacturer’s recommendations. 
Safety and immunogenicity assessments will be made up to 2 years 
following the last dose administration. Specified safety data will be 
reviewed by an internal safety review committee (iSRC) and a data 
safety monitoring board (DSMB) on a pre-defined schedule. 
Trial Population 
Key Inclusion 
Criteria: 
1. Healthy male and female subjects aged 18 to 40 years inclusive. 
2. Expected to be compliant with protocol procedures and available for 
clinical follow-up through the last planned visit. 
3. Physical examination and laboratory results without clinically 
significant findings. 
The full list of inclusion criteria is provided in the protocol. 
Trial Population 
Key Exclusion 
Criteria: 
1. Receipt of licensed or investigational rabies vaccine prior to the 
administration of the trial vaccine. 
2. History of potential immune mediated disease. 
3. Known allergy to any component of CV7202 or Rabipur®. 
The full list of exclusion criteria is provided in the protocol. 
Number of 
Subjects: 
Approximately 52 subjects will be enrolled. 
Vaccination 
Groups and 
Duration: 
 
Trial 
Product 
Composition 
Dosing 
Day 1 
Day 8 
Day 29 
N 
N 
N 
Group 1 
Rabipur® 
N/A 
10 
10 
10 
Group 2* 
CV7202 
5 µg mRNA 
10 
NA 
N/A 
Group 3 
1 µg mRNA 
16 
8 
 Group 3a** 
Group 4 
2 µg mRNA 
16 
8 
 Group 4a** 
Total CV7202 
 
 
42 
 
16 
* Note that enrolment in Group 2 was already completed at the time this 
protocol amendment was issued. 
** ‘a’ groups are a subset consisting of 8 subjects of Groups 3 and 4 
scheduled to receive a first dose on Day 1 and a second dose on Day 29. 
Measurements and 
Assessments: 
Due to the exploratory nature of this trial only descriptive statistics will 
be used, no confirmatory statistical inference will be performed. 
Safety set: This is the subset of subjects, who have received at least 
one dose of the candidate rabies mRNA vaccine CV7202 or the active 
control Rabipur® and for whom any post-Day 1 safety data are 
available. The analysis of safety will be performed on this population. 
Full-analysis (FA) set: This is the subset of the Safety Set with 
subjects who have the baseline sample and at least one additional 
blood sample available for VNT analysis. This analysis set is the 
primary analysis set for all immunogenicity objectives. 

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Primary and secondary safety and reactogenicity will be assessed as 
follows: 
1. AEs 
(type, 
intensity, 
frequency 
and 
relationship 
to 
vaccination), i.e. incidence and severity of AEs for both 
solicited local and systemic events (reported on the day of 
vaccination and the 7 subsequent days [Days 1-8]) and 
unsolicited events (reported on the day of vaccination and the 
28 subsequent days [Days 1-29]). 
2. SAEs, MAAEs and AEs leading to trial or vaccine withdrawal up to 
12 months post last dose. After Visit 15 (Month 12), only SAEs and 
MAAEs that according to the investigator are considered to be 
related to study vaccination will be collected. 
3. Intercurrent medical conditions and AESIs throughout the trial. 
4. Local reactogenicity assessment of injection site in all subjects. 
Further safety assessments will be conducted based on vital signs 
and laboratory assessments. Results will be summarized in tables and 
supported by subject level listings. 
Secondary immunogenicity endpoints: 
1. Number and percentage of subjects having VNTs ≥0.5 IU/ml on 
Days 1, 15, 43, and 12, 18 and 24 months post last dose. 
2. Individual functional antibody titers, GMTs and range of titers in sera 
collected on Days 1, 8, 15, 29, 36, 43, 57, and 12, 18 and 24 months 
post last dose. 
Further immunogenicity assessments will be based on VNTs, RABV-
G-specific immunoglobulins (Ig) IgG, IgM and IgA serum antibodies 
and other immunogenicity-related parameters throughout the duration 
of the trial. Results will be summarized in tables, figures and 
supported by subject level listings. 
No statistically-based sample size estimation was performed. 
 

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2 Schedule of Activities 
Table 2.1 
Schedule of Activities 
Notes: 
M6 corresponds to Day 181 (1-dose groups) and Day 209 [2-dose groups and Group 1 (Rabipur®)]. 
M12 corresponds to Day 365 (1-dose groups) and Day 393 [2-dose groups and Group 1 (Rabipur®)]. 
M18 corresponds to Day 547 (all groups). 
M24 corresponds to Day 729 (all groups). 
Vaccinations planned at Visit 3 (Dose 1 for Groups 1 to 4), Visit 5 (Dose 2 Rabipur® for Group 1), Visit 8 (Dose 2 for Groups 3a and 4a, Dose 3 Rabipur® for Group 1). 
* The pre-screening and screening visits can be performed on the same day. 
** The Day 2 and Day 30 visits should be performed at around 24 +/- 2 hours after the vaccination. 
† Note that for subjects in Groups 1 and 2, who were already enrolled and vaccinated before Protocol Amendment 1 was issued, Visit 4 occurred on Day 3 and Visit 9 occurred on Day 31 as planned in the original protocol. 
§ Blood drawn at the pre-screening visit will be kept for retrospective measurement of TSH, thyroid antibodies and ANA following the occurrence of clinical autoimmune events (other autoantibodies might be investigated as well depending on the 
Visit Type 
 
Pre-
screening 
Screening 
Clinic visit 
Phone 
call 
Clinic visit 
Phone 
call 
Clinic visit 
Clinic visit/*** 
Trial Day 
 
-90 to -1* 
-30 to -1* 
1 
2† 
3 
8 
10 
15 
29 
30#† 
31 
36 
43 
57 
91 
M6 
M12 
M18 
M24 
Visit Window (days) 
 
N/A 
N/A 
N/A 
+/- 2** 
- 
+1 
-1/+2 
-1/+2 
+/- 2 
+/- 2** 
- 
-1/+2 
+/- 2 
+/- 2 
+/- 7 
+/- 14 
+ 15-90 
+/- 30 
+ 31-90 
+/- 30 
+ 31-90 
+/- 30 
+31-180 
Visit Number 
 
1 
2 
3 
4 
- 
5 
6 
7 
8 
9 
- 
10 
11 
12 
13 
14 
14A 
15 
15A 
16 
16A 
17 
17A 
Procedure 
References 
 
 
 
 
CV7202 
groups 
only 
 
Group 
1 only 
 
 
Group
s 1, 3a 
and 4a 
only 
CV720
2 
groups 
only 
 
 
 
 
 
 
 
 
 
 
 
 
Signed Informed Consent a 
9.4.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical History 
9.4.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/Exclusion criteria  
6.1, 6.2, 9.4.1, 9.4.2, 9.4.3 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccine delay recommendations 
6.3, 9.4.3, 9.4.6, 9.4.9 
 
 
X 
 
 
X 
 
 
X# 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
9.4.1 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy Test 
9.4.2, 9.4.3, 9.4.6, 9.4.9 
 
X b 
X c 
 
 
X c 
 
 
X# c 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination 
CV7202 
9.4.3, 9.4.9 
 
 
X 
 
 
 
 
 
X d 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rabipur® 
9.4.3, 9.4.6, 9.4.9 
 
 
X 
 
 
X 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety monitoring 
Physical Examination e 
9.4.2-9.4.11, 9.4.14, 9.4.15, 9.4.17, 0 
 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
X 
X 
 
 
X 
X 
 
 
X 
X 
12-lead Electrocardiogram 
9.4.2 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs f 
9.4.1, 9.4.3-9.4.11, 9.4.17, 0 
X 
 
X 
X 
 
X 
X 
X 
X# 
X 
 
X 
 
 
 
 
 
X 
X 
 
 
X 
X 
Post-injection vaccination site reactogenicity assessmentg 
9.4.3-9.4.7, 9.4.9-9.4.10 
 
 
X 
X 
 
X 
X 
 
X# 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary dispensed/training h 
9.4.3, 9.4.5, 9.4.9 
 
 
X 
 
 
X 
 
 
X# 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Diary review/reminder h 
9.4.4-9.4.14 
 
 
 
X 
 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Diary collection h 
9.4.5, 9.4.9, 9.4.14 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
X  
 
 
 
 
 
 
 
 
 
Assess all post-dose solicited AEs 
9.4.3-9.4.12 
 
 
X 
X 
X 
X 
X 
X 
X# 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Assess all post-dose unsolicited AEs 
9.4.3-9.4.14 
 
 
X 
X 
X 
X 
X 
X 
X# 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
Assess all SAEs  
9.4.3-9.4.17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Assess all MAAEs  
9.4.3-9.4.17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Assess AEs leading to premature withdrawal 
9.4.3-9.4.17 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Assess intercurrent medical conditions  
9.4.3-0 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess Concomitant Medications/Vaccinations 
9.4.2-0 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess AESIs  
9.4.3-0 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assess SAEs related to study vaccination  m 
9.4.3-0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
Assess MAAEs related to study vaccination m 
9.4.3-0 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
X 
X 
Safety Lab j (~9 ml) 
9.4.2-9.4.5, 9.4.8-9.4.11, 9.4.14-9.4.17 
 
X j,k 
X j,k 
X j,k 
 
X j 
 
X j 
X j 
X j,k 
 
X j 
 
X j 
X j 
X j 
X j 
X j 
X j 
 
 
Xo 
Xo 
TSH, Thyroid antibodies, ANA (~3 ml)§ 
9.5.2 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Immunogenicity 
VNTs (serum) i (~18ml) 
9.4.3, 9.4.5, 9.4.8, 9.4.9, 9.4.11-0 
 
 
X 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X n 
X n 
X n 
X n 
IgM/ IgG/ IgA ELISA (serum) i (~6 ml) 
9.4.3, 9.4.5, 9.4.8, 9.4.9, 9.4.11-0 
 
 
X 
 
 
X 
 
X 
X 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X n 
X n 
X n 
X n 
Cellular immune response and leukocyte phenotyping 
(PBMCs) i, l (~40-60 ml) 
9.4.3, 9.4.5, 9.4.11, 9.4.15-9.4.17 
 
 
X 
 
 
X 
 
 
 
 
 
X 
 
 
X 
X 
X 
X 
X 
 
 
 
 
Cytokine assessment (serum)  i, l (~6 ml) 
9.4.3-9.4.5, 9.4.9-9.4.11 
 
 
X‡ 
X 
 
X 
 
 
X#, ‡ 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Transcriptome profiling (PBMCs)  i, l  (~10ml) 
9.4.3, 9.4.4, 9.4.9, 9.4.10 
 
 
X 
X 
 
X 
 
 
X# 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Immune receptor sequencing (PAXgene DNA) i (~5ml) 
9.4.3, 9.4.5, 9.4.9, 9.4.11, 9.4.14-9.4.17 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
Maximum total blood volume (ml) 
Table 9.3 
3 
11 
120 
25 
0 
94 
0 
33 
60 
25 
0 
94 
24 
38 
78 
78 
78 
78 
78 
24 
24 
24 
24 
Trial end 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 

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clinical autoimmune event). 
# =Only for subjects receiving vaccination (Dose 2 for Groups 3a and 4a, Dose 3 Rabipur® for Group 1) 
‡ Two blood samples for cytokine assessment will be drawn on the days of vaccination, including one pre-vaccination sample and one sample at 4 hours post-vaccination (Only for CV7202 groups). 
*** The optional Visits 14A, 15A, 16A and 17A should only take place in case the respective visit could not be conducted as described in the protocol. In case Visit 14, 15, 16 or 17 cannot take place on site due to the public health emergency 
related to COVID-19, safety information should be collected via a phone call within the protocol-allowed time interval for the respective visit. However, if the investigator judges that the benefits of a site visit outweigh the risks based on clinical 
symptoms, the visit should take place on site. In this case, all procedures as indicated in this table for the respective time point should be performed, if possible. If the information was collected via a phone call, the respective Visit A should be 
scheduled on site within the protocol-allowed time interval and all indicated procedures, including blood sampling, should be performed. Also, in case the visit was conducted on site but not all procedures could be performed, the respective 
Visit A should be scheduled on site within the protocol-allowed time interval. 
Abbreviations: AE=Adverse event; AESI = Adverse event of special interest; ANA = Antinuclear antibody; ELISA = Enzyme-linked immunosorbent assay; Ig = Immunoglobulin; MAAE = Medically-attended adverse event;  
PBMC = Peripheral blood mononuclear cell: SAE = Serious adverse event; TSH = Thyroid-stimulating hormone; VNT = Virus-neutralizing antibody titers;  
a Informed consent form(s) signed prior to any procedures. 
b In women of childbearing potential, serum pregnancy test. A 3 ml blood sample will be taken. 
c In women of childbearing potential, urine pregnancy tests will be performed before each vaccination, unless the serum pregnancy test was performed less than 3 days before. 
d Second vaccination of CV7202 will be given only to 8 subjects in Groups 3 and 4 (i.e. Groups 3a and 4a). 
e Physical examination and vital signs must be performed/analyzed by a qualified healthcare professional. 
f Vital signs to be checked: body temperature, pulse, blood pressure. Vital signs will be measured pre- and post-vaccination prior to discharge. Subjects will be observed for 4 hours following each vaccination; vital signs must be within normal or 
clinically non -relevant abnormal ranges or have returned to pre-vaccination values for the subject to be discharged from the phase I Unit. 
g All vaccinated subjects will undergo vaccination site reactogenicity assessment at 1 hour post-vaccination on the day of vaccination (Day 1, Day 8 and Day 29) and 1 or 2 days after each vaccination (Day 2 or 3, Day 10 and Day 30 or 31). Note 
that Days 3 and 31 were planned in the original protocol and only apply to subjects in Groups 1 and 2 who were already enrolled and vaccinated before this protocol amendment was issued. Local reactions (injection site pain, redness, swelling 
and itching) will be assessed on an intensity scale of absent, mild, moderate and severe. 
h Solicited and unsolicited AE diaries. Solicited AEs occurring on the day of vaccination (Day 1, Day 8 and Day 29) and for the following 7 days will be recorded by the subject on the diary card. The diary card will be reviewed on Day 2 or 3, 8, 10, 
15 29, 30 or 31, 36, 43 and 57. Unsolicited AEs occurring on the day of vaccination (Day 1, Day 8 and Day 29) and for the following 28 days will be recorded by the subject on the diary card. 
i The VNT serum sample is intended as the baseline value and must be taken before vaccination on Day 1 and Day 29. 
j Hematology (complete blood count, including differential and platelets), biochemistry. 
k Coagulation (activated partial thromboplastin time [aPTT]) and prothrombin time/international normalized ratio (INR) will be performed at the following time points: Screening, Day 1, Day 2 or 3 and Day 30 or 31. 
l In the first 5 subjects in Group 2 and all subjects in Groups 3 and 4. 60 ml for the baseline (Day 1) time point, 40 ml for subsequent blood draws. 
m At each study visit/contact preceding Month 18, SAE and MAAEs considered as related to study vaccination were collected as part of all SAEs and MAAEs. 
n At Month 18 and Month 24, VNTs and IgG assessments will be performed only in subjects with detectable RABV-G-specific IgG at 6 months after the last vaccination or Day 91 if the Month 6 blood sample is not available. 
o If no blood sampling could be performed at Visit 15 and the optional Visit 15A, the end-of-trial blood sample for safety assessment may be performed at Visit 17 (Month 24). 

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Table 2.2 
Staggered Enrolment and Dose Escalation for Groups 2 to 4 (Dose 1) with Minimum Time Intervals* 
Week#* 
Group #2 
Groups #3 - #4 
Dose 1 (Day 1) 
Review 
Dose 1 (Day 1) 
Review 
1 
#1 (enrol) Day 1 
 
 
 
#2 - #3 Day 3 
 
 
 
2 
#4 - #5 Day 1 
iSRC** 
 
 
3 
#6 - #10 (enrol)  
 
 
 
7 
 
DSMB GO/NO GO (next dose level) 
 
 
8 
 
 
#1 (enrol) Day 1 
 
 
 
#2 Day 3 
 
9 
 
 
#3 - #4 Day 1 
iSRC** 
10 -11 
 
 
#5 - #16 (enrol)§ 
 
12 
 
 
 
DSMB GO/NO GO (next dose level) 
13 – 42 
 
 
Enrolment cycle for Group 4† 
DSMB (Data safety monitoring board) provides recommendation to proceed or not with dose-escalation; iSRC = Internal safety review committee; Day 1 corresponds to Monday, Day 3 corresponds to Wednesday. 
* These intervals may be prolonged at the discretion of the investigator or upon request of the sponsor or DSMB for safety or operational reasons; 
** The iSRC will take place only once the last subject in the sentinel group (first 5 subjects of Group 2, first 4 subjects in Groups 3 and 4 and subsequent 6 subjects in Groups 3 and 4) has been vaccinated and followed up for at least 2 working days. 
§ The staggered enrolment for the initial 4 subjects may be extended to the subsequent subjects in Groups 3 or 4. The number of subjects in this extended staggered enrolment may be further established by the investigator, sponsor or DSMB based on the data 
obtained in earlier enrolled subjects in these groups. 
† Enrolment in Group 4 can proceed as for Group 3 with a duration of a minimum of 7 weeks. A slower enrolment schedule can be followed in agreement with the investigator and sponsor, if needed with input from the iSRC or DSMB. 
 

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3 Introduction 
Rabies is a viral zoonosis which causes acute encephalitis in mammals including 
humans. The disease is virtually always fatal once clinical symptoms develop. There 
are an estimated 59 000 rabies-related deaths each year [2]. The virus is endemic 
worldwide, but human mortality due to rabies differs markedly from continent to 
continent [3]. Recognizing that rabies remains a neglected disease in Asia and Africa 
despite the existence of safe and effective vaccines, the World Health Organization 
(WHO) Strategic Advisory Group of Experts on Immunization (SAGE), established a 
working group on rabies vaccines and immunoglobulins (Igs) in 2016 to review 
scientific evidence, programmatic considerations and vaccine regimens of existing 
therapies, and also to evaluate the potential impact of new biologicals [4]. 
Existing rabies vaccines can be used for both pre-exposure and post-exposure 
prophylaxis. Although pre-exposure prophylaxis is primarily used by animal handlers, 
laboratory personnel, veterinarians and forestry workers in Europe and North 
America, rabies prophylaxis is also appropriate for travelers to high-risk regions [5]. 
The US Centers for Disease Control and Prevention (CDC) reported a range of 
approximately 16–200 possible exposures per 100 000 travelers [6], while a 2008 
study from Thailand assessed the risk of rabies exposure among 870 backpackers 
and found that 3.6% of them had been licked and 0.7% had been bitten by an animal 
[7]. Despite the demonstrated risk of rabies exposure to travelers in high-risk regions, 
compliance with the three injection primary vaccination series is suboptimal. Gautret 
and Parola reported that 76% of travelers for whom vaccination was recommended 
by the travel clinic physician either declined vaccination or did not have time to 
complete the primary three-dose vaccination series [8]. Similarly, in canine rabies 
infected areas, such as countries of Southeast Asia, pre-exposure prophylaxis of 
children has been proposed but not implemented. Children under the age of 15 are 
the most frequently exposed, representing 40% of human exposures [9], and would 
benefit from pre-exposure prophylaxis. A study assessing pre-exposure prophylaxis 
against rabies among school-aged children in Bangalore, India, suggests that this 
approach may be a useful tool for protecting children in highly endemic regions [10]. 
Although safe and effective, existing vaccines have limitations: they require 
refrigeration, a three-injection primary series for pre-exposure prophylaxis and virus 
inactivation steps during manufacturing which may lead to lot failure. In recognizing 
the ongoing need for an effective and convenient rabies vaccine, CureVac proposes 
to apply its proprietary messenger ribonucleic acid (mRNA) platform to develop a 
shelf-stable, polygeline-free, safe and effective vaccine which can be used for both 
pre-exposure and post-exposure prophylaxis in humans. 
3.1 RNActive® technology 
During translation mRNA serves as the template for protein synthesis and mRNA-
based vaccines offer the possibility to vaccinate against any infectious disease that is 
preventable by providing or increasing the immune response against the protein 
antigen. However, mRNA molecules are highly unstable under physiological 
conditions, limiting their therapeutic application [11]. Research into achieving 
ribonucleic acid (RNA) stability has led to the development of different RNA delivery 
systems [12], including CureVac’s mRNA technology (RNActive®). 

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The RNActive® technology employs formulated mRNA as a vaccine vector to allow 
for direct translation of target protein antigens within a recipient’s cells. RNActive® 
vaccines formulated with lipid nanoparticles (LNPs) consist of an mRNA encoding the 
antigen of interest, which is encapsulated by LNPs. The mRNA provides strong 
antigen expression. The encapsulation of mRNA in LNPs is intended to facilitate and 
enhance the uptake of mRNA by cells. As a result of mRNA translation, antigen 
presentation and immune stimulation, strong and persistent adaptive immune 
responses against the encoded antigens are induced in animal models [13, 14]. 
A phase I trial evaluating the first candidate rabies mRNA vaccine formulated with 
protamine (CV-7201-102) induced boostable virus-neutralizing antibodies after 
needle-free (intradermal [i.d.] or intramuscular [i.m.]) injection, whereas needle-based 
(i.d. and i.m.) injection was ineffective [15]. The vaccine appeared generally safe with 
an acceptable reactogenicity profile. This trial provided important guidance for 
advances in CureVac’s mRNA technology (RNActive®) particularly with respect to 
development of improved vaccine candidates formulated with lipid nanoparticles 
(LNP), which have been demonstrated to efficiently deliver mRNA in vivo to the 
cytoplasm of cells, where the encoded antigens are translated into proteins able to 
elicit antigen-specific immune responses [16]. 
The new candidate rabies mRNA vaccine, CV7202, is composed of R1803 (the 
identical active pharmaceutical ingredient [API], used in CV-7201-102), encapsulated 
in the novel LNP delivery system. mRNA-based vaccines based on this new delivery 
system have been shown to induce substantially higher and more durable virus-
neutralizing antibody titers (VNTs) compared with protamine-formulated vaccines in 
several animal models [13] and elicit comparable responses in NHPs to those seen 
with licensed vaccines [17].  
The current clinical study CV-7202-104 is ongoing with 10 subjects having received 
CV7202 up to date and being followed-up. Therefore, only preliminary clinical safety 
and immunogenicity data are available at this time. 
The proposed trial will assess the safety, reactogenicity and immunogenicity of 
different doses of CV7202 in healthy adult subjects (18–40 years of age) 
administered i.m. as one or two doses. The active control, Rabipur® will be 
administered in previously unvaccinated subjects, as the three recommended doses. 
The trial will be conducted in accordance with the protocol, the ICH-GCP Guidelines 
[1], European Medicines Agency (EMA) guidelines for first-in-human (FIH) clinical 
trials [22] and applicable regulatory requirements. 
Refer to the current Investigator’s Brochure (IB) for CV7202 for additional product 
information [17]. 

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4 Objectives and Endpoints 
The primary, secondary, and exploratory objectives and endpoints of this trial are 
listed in sections 4.1 and 4.2. 
4.1 Objectives 
Primary Objective: 
To assess the safety and reactogenicity profile of CV7202 administered i.m. to 
healthy adults (18–40 years old), as a range of doses (1, 2 and 5 µg) in one- or two-
dose regimens. 
Secondary Objectives: 
For safety 
 To assess the safety profile of CV7202 administered i.m. to healthy adults 
(18-40 years old), as a range of doses (1, 2 and 5 µg) in one- or two-dose 
regimens in the period from 12 to 24 months post last dose. 
For the characterization of the humoral immune response 
 To evaluate the potential protective immune responses to CV7202 and Rabipur® 
in healthy adults (18–40 years old), by assessing the percentages of subjects with 
rabies-specific serum VNTs ≥0.5 IU/ml. 
 To evaluate the immunogenicity (VNTs) of CV7202 administered to healthy adults 
(18–40 years old), as a range of doses (1, 2 and 5 µg) in one- or two-dose 
regimens and the immunogenicity of Rabipur® administered in a 3-dose regimen. 
Exploratory Objectives: 
For the evaluation of the innate immune response 
 To evaluate the innate immune response to one or two doses of CV7202 
compared with baseline. 
For the evaluation of antigen specific T-cell response 
 To evaluate the frequencies and functionalities of rabies virus glycoprotein 
(RABV-G)-specific T cells after one or two doses of CV7202 compared with 
baseline. 
For the evaluation and characterization of the B-cell response 
 To evaluate the frequencies of RABV-G-specific B cells after one or two doses of 
CV7202 compared with baseline. 
 To evaluate the effect of vaccination on B-cell phenotype and activation after one 
or two doses of CV7202 compared with baseline. 
 To evaluate the effect of vaccination on B-cell clonality after one or two doses of 
CV7202 compared with baseline. 
For the characterization of the humoral immune response 
 To evaluate RABV-G-specific antibody responses throughout the trial including 
the follow-up period by assessing IgM, IgG and IgA levels. 

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 To characterize the nature and quality of the RABV-G-specific antibody response, 
by measuring the serum affinity and avidity after one or two doses of CV7202 and 
the breadth of neutralization against heterologous lyssaviruses with variant 
epitopes. 
4.2 Endpoints 
Primary Endpoints: 
 The percentages of subjects with, and the frequencies and intensities of solicited 
local adverse events (AEs) reported on the day of vaccination and the 7 
subsequent days (Days 1-8). 
 The percentages of subjects with, and the frequencies, intensities and relationship 
to vaccination, of solicited systemic AEs reported on the day of vaccination and 
the 7 subsequent days (Days 1-8). 
 The duration (in days) of solicited local AE, of solicited systemic AE and of the 
individual solicited AEs. 
 The percentages of subjects with and frequencies and intensities of any 
unsolicited and related unsolicited AEs reported on the day of vaccination and the 
28 subsequent days (Days 1-29). 
 The percentages of subjects with and frequencies and relationship to vaccination, 
of any serious adverse events (SAEs) and any MAAEs up to 12 months post last 
dose. 
 The percentages of subjects with and frequencies and relationship to vaccination 
of any adverse events of special interest (AESIs) up to 12 months post 
vaccination. 
Secondary Endpoints: 
For safety 
 The percentages of subjects with and frequencies of SAEs and MAAEs related to 
study vaccination from 12 months post last dose up to 24 months post last dose 
(trial end). 
 The percentages of subjects with and frequencies and relationship to vaccination 
of any AESIs from 12 months post last dose up to 24 months post last dose (trial 
end). 
For the characterization of the humoral immune response 
 Percentages of subjects with rabies-specific serum VNTs ≥0.5 IU/ml by trial group 
on Days 1 (pre-vaccination), 15, 43, and 12, 18* and 24* months post last dose. 
 Serum geometric mean titers (GMTs) of VNTs by trial group on Days 1, 8, 15, 29, 
36, 43, 57, 91, and 6 and 12, 18* and 24* months post-last dose. 
* Will be performed only in subjects with detectable RABV-G-specific IgG at 6 months 
after the last vaccination or Day 91 if the Month 6 blood sample is not available. 

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Exploratory Endpoints: 
For the evaluation of the innate immune response: 
 Serum cytokine concentrations* including but not limited to CXCL10, CCL3, IL-6, 
TNF-α and IFN-γ, at pre-vaccination and 4 hours post-vaccination on Day 1, and 
Days 2 or 3** and 8 after each vaccination. 
 Transcriptome profiling* on the day of vaccination at pre-vaccination, and Days 2 
or 3** and 8 after each vaccination. 
* Will be performed in the first 5 subjects in Group 2 (** on Day 3) and all subjects in 
Groups 3 and 4 (** on Day 2). Note that Day 3 was planned in the original protocol 
and only applies to subjects in Groups 1 and 2 who were already enrolled and 
vaccinated before this protocol amendment was issued. Day 2 applies to all other 
subjects. 
For the evaluation of antigen specific T-cell response: 
 The frequencies and functionalities of RABV-G-specific T cells in peripheral blood 
from the first 5 subjects in Group 2 and all subjects in Groups 3 and 4 on Days 1, 
8, 36, 91*, and 6* and 12* months post-last dose. 
* For groups that have shown a significant T-cell response at Day 8 or 36 compared 
to baseline. 
For the evaluation and characterization of the B cell response 
 The frequencies of RABV-G-specific B cells in peripheral blood from the first 
5 subjects in Group 2 and all subjects in Groups 3 and 4 on Days 1, 8, 36, 91*, 
and 6* and 12* months post-last dose. 
 The frequencies and activation status of phenotypically distinct subsets of B cell 
populations, including but not limited to naïve and memory B cells, plasmablasts 
and plasma cells for the first 5 subjects in Group 2 and all subjects in Groups 3 
and 4 on Days 1, 8, 36, 91*, and 6* and 12* months post-last dose. 
 Sequencing of B-cell receptors (BCR) of circulating B cells on Days 1, 8, 29, 36, 
57, 91*, and 6* and 12* months post-last dose. 
* For groups that have shown a significant B-cell response at Day 8 or 36 compared 
to baseline. 
For the characterization of the humoral immune response: 
 RABV-G-specific IgM, IgG and IgA levels measured by ELISA on Days 1, 8, 15, 
29, 36, 43, 57, 91, and 6 and 12 months post-last dose. 
 RABV-G-specific IgG levels measured by ELISA 18* and 24* months post-last 
dose. 
 Identification of epitopes recognized by vaccine-induced antibodies on Days 1, 
15, 43, and 2, 6 and 12 months post-last dose**. 
 Measurement of RABV-G-specific antibody avidity and affinity on Days 1, 15, 43, 
and 2, 6 and 12 months post-last dose**. 

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 Measurement of VNTs against additional heterologous lyssaviruses on Days 1, 
15, 43, and 2, 6 and 12 months post-last dose**. 
* Will be performed only in subjects with detectable RABV-G-specific IgG at 6 months 
after the last vaccination or Day 91 if the Month 6 blood sample is not available. 
** Will be performed only on selected samples with VNT >0.5 IU/ml. 

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5 Trial Design 
5.1 Overall Design 
This is a non-randomized, open label, controlled, dose-escalation, phase I clinical 
trial to evaluate the safety, reactogenicity and immunogenicity of one or two i.m. 
administrations of candidate rabies mRNA vaccine CV7202 in healthy adult subjects. 
Approximately 52 subjects will be enrolled sequentially in up to 4 trial groups to 
receive either a dose of CV7202 containing different mRNA content or Rabipur®. In a 
first CV7202 group, 10 subjects have received a dose containing 5 µg mRNA. A dose 
of 1 or 2 µg mRNA will be administered to 2 additional groups of 16 subjects each, of 
whom 8 in each group will be administered a second dose 28 days later. A control 
group of 10 subjects will receive 3 doses of the licensed vaccine Rabipur® according 
to the manufacturer’s recommendations. Safety and immunogenicity assessments 
will be made up to 2 years following the last dose administration. Specified safety 
data will be reviewed by an internal safety review committee (iSRC) and a data safety 
monitoring board (DSMB) on a pre-defined schedule. 
Figure 5.1 
CV-7202-104 Trial Design 
 
5.1.1 Dose-finding Schedule, Enrolment Plan 
Enrolment will be staggered in Groups 2 to 4 to ensure the safety of the participating 
subjects (Table 2.2). Enrolment into Group 1 (1.0 ml Rabipur®) will not be staggered, 
since the clinical safety of Rabipur® is well-established. 
CV7202 Groups: In Group 2, the first 5 subjects sequentially received the first dose 
with a 2 working-day interval between subject #1 (e.g. Week 1 – Day 1 – Monday) 
and subjects #2 and #3 (e.g. Week 1- Day 3 – Wednesday) and were observed for 
2 days. Subjects #4 and #5 received their first dose one week after subject #1 (e.g. 
Week 2 – Day 1 – Monday). Once the fifth subject in the group had been vaccinated 
and followed up for at least 2 working days, safety data for the first 5 subjects were 
Dose 1
Dose 2
24 months post 
last dose
End of Trial
Day 1
Day 8
Day 29
Dose 1
Dose 3
Dose 2
Screening
from Day -30
Pre-screening
from Day -90
CV7202 Group 2 (N=10)*
CV7202 Groups 3 and 4 
(N=16 per group)**
CV7202 Groups 3a and 4a
(N=8 per group from Groups 3 and 4)
Rabipur® Group 1 (N=10)
Non-staggered enrolment
Day 1
Day 29
CV7202 Groups 2 to 4 (N=8)
† The number of subjects in this extended staggered enrollment may be further established by the investigator, sponsor or DSMB based on the data obtained 
in first 4 enrolled subjects. 
* Staggered enrolment performed for CV7202 Group 2
Subjects # 6-10
iSRC and DSMB review
Endorsement of iSRC and 
DSMB
Subjects # 1-5
Internal review and NO GO 
decision for enrolment of 
additional subjects
** Staggered enrolment to be performed for CV7202 Groups 3 and 4 (min. 3 weeks)
Subjects # 5-10†
iSRC review
DSMB review and GO/NO 
GO from Group 3 to Group 4
Subjects # 1-4
Stop enrolment
Subjects # 11-16

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reviewed by the iSRC. Following iSRC approval, the remaining 5 subjects in the 
group were enrolled and received the first dose. 
In Groups 3 and 4, the first 4 subjects will also be enrolled using a staggered 
approach. The first 4 subjects will sequentially receive the first dose with a 2 working-
day interval between subject #1 (e.g. Week 1 – Day 1 – Monday) and subject #2 (e.g. 
Week 1- Day 3 – Wednesday) and will be observed for 2 days. A phone call will be 
performed after 2 days to collect safety information. Subjects #3 and #4 will receive 
their first dose at the earliest one week after subject #1 (e.g. Week 2 – Day 1 – 
Monday). All data obtained from these sentinel subjects (at least until 2 days after the 
vaccinations) must be entered continuously into the eCRF, at the latest within 24 
hours, to allow a timely safety assessment. Once the fourth subject in the group has 
been vaccinated and followed up for at least 2 working days, safety data recorded in 
the eCRF for the first 4 subjects will be reviewed by the iSRC. Following iSRC 
approval, the remaining 12 subjects in the group will be enrolled and receive the first 
dose. In addition, the staggered enrolment may be extended to the subsequent 
subjects to be enrolled in Groups 3 and 4. The number of subjects in this extended 
staggered enrolment may be further established by the investigator, sponsor or 
DSMB based on the data obtained in earlier enrolled subjects in these groups. The 
DSMB will review safety data for an observation period of 28 days following 
administration of the first dose for all subjects in each dose group prior to enrolment 
into the next dose group (i.e. from the 1 µg dose level Group 3 to the 2 µg dose level 
Group 4). Before administration of the second dose of CV7202, the iSRC will review 
all available accumulated safety data from all subjects having already received a 
second dose. 
Enrolment in each dose group can proceed as follows for a duration of a minimum of 
7 weeks per group. A slower enrolment schedule can be followed in agreement with 
the investigator and sponsor, if needed with input from the iSRC or DSMB: 
 Week 1: Start enrolment in Group 3 (up to 2 subjects). Subject #1 on Day 1, 
subject #2 on Day 3. 
 Week 2: Enrol subjects #3 and 4 on Day 1 and prepare iSRC review of AEs and 
available safety data following 2 days’ observation.  
 From Week 3: Enrol the remainder of the subjects (i.e. 12 subjects for Groups 3 
and 4). Extended staggered enrolment (e.g. for subjects #5 to 10 or beyond) can 
be implemented as needed. 
 From Week 7: Collect solicited AEs, unsolicited AEs, SAEs and safety laboratory 
data, and prepare DSMB review. 
 Favorable DSMB decision: Start the enrolment cycle for the next dose level 
group. 
The staggered approach to dose administration does not apply to Dose 2. 
5.1.2 Stopping Rules 
For dose escalation (group) 
At each planned safety review, safety data will be reviewed and a GO/NO GO 
decision made accordingly for enrolment of further subjects and administration of 
subsequent doses. 

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Enrolment or administration at the given dose level will be temporally halted 
and only continued after DSMB approval and approval by the competent 
authority following the occurrence of: 
 Any related SAE in the opinion of the principal investigator (PI), the DSMB and/or 
the iSRC. 
 Related severe AEs of the same kind in ≥ 20% of the subjects in one group with 
the following exceptions: 
 Transient grade 3 chills, fatigue, headache, fever, myalgia or arthralgia 
resolving within 24 hours to grade ≤2. 
 Transient grade 3 local AEs reducing to grade ≤2 within 48 hours. 
Based on the review of the data, the DSMB will decide about temporary or 
permanent stopping of dosing in the given and eventually also lower dose groups 
(pertaining to the 2nd dose administration). After a temporary halt further measures 
for safety monitoring (i.e. additional safety visits including safety blood sampling at 
additional time points) may also be introduced based on DSMB recommendation. 
For further CV7202 dose administration (subject) 
Subjects must not receive a second dose of CV7202 in the event of: 
 Occurrence of an allergic/anaphylactic reaction after the first dose. 
 Any related SAE in the opinion of the PI, the DSMB and/or the iSRC. 
 Any related severe (grade 3) AEs with the following exceptions: 
 Transient grade 3 chills, fatigue, headache, fever, myalgia or arthralgia 
resolving within 24 hours to grade ≤2. 
 Transient grade 3 local reactions resolving to grade ≤2 within 48 hours. 
If these reactions occur, the subject must not receive additional vaccinations but is 
encouraged to continue in trial participation for safety reasons, including collection of 
safety blood samples. Immunogenicity assessments may be performed at the 
investigator’s discretion and if the subject agrees. 
5.1.3 Timing of Blood Collection for Safety and Immunogenicity 
Parameters 
Blood samples will be drawn as follows: 
 Safety assessments: Pre-screening, screening, Days 1, 2 or 3**, 8, 15, 29, 30 or 
31**, 36, 57, Day 91, Month 6* (Day 181 [1-dose groups] and Day 209 [2-dose 
groups and Group 1 (Rabipur®)]) and Month 12* (Day 365 [1-dose groups] and 
Day 393 [2-dose groups and Group 1 (Rabipur®)]). 
* In case a site visit is not possible due to the public health emergency related to 
COVID-19, the blood sample for safety assessment at Month 6 and Month 12 
should be collected at Visit 14A and Visit 15A, respectively, only in case 
restrictive measures related to COVID-19 no longer prevent site visits (refer to 
Section 9.4.16 and 9.4.17 for details). If no blood sampling could be performed at 
Visit 15 and 15A (Month 12), the end-of-trial blood sample for safety assessment 
may be performed at Visit 17 (Month 24). 

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 Immunogenicity assessments: Days 1, 2 or 3**, 8, 15, 29, 30 or 31**, 36, 43, 57, 
Day 91, Month 6* (Day 181 [1-dose groups] and Day 209 [2-dose groups and Group 
1 (Rabipur®)]), Month 12* (Day 365 [1-dose groups] and Day 393 [2-dose groups 
and Group 1 (Rabipur®)]), Month 18* (Day 547) and Month 24* (Day 729). 
* In case a site visit is not possible due to the public health emergency related to 
COVID-19, the blood sample for immunogenicity assessments should be collected 
at Visits A, only in case restrictive measures related to COVID-19 no longer prevent 
site visits (refer to Sections 9.4.16 to 9.4.19 for details). 
** Days 3 and 31 were planned in the original protocol and only apply to subjects in 
Groups 1 and 2 who were already enrolled and vaccinated before this protocol 
amendment was issued. Days 2 and 30 apply to all other subjects.  
Refer to the schedule of activities in Table 2.1 and Section 9.5. 
5.2 Subject and Trial Completion 
Subjects will be enrolled at pre-screening (Day -90 to -1) to receive either CV7202 
starting Day 1 as 1 dose or 2 doses (at least 28 days apart), or 3 doses of control 
vaccine (Rabipur®). Follow-up for safety and immunogenicity is planned up to 
24 months after the last dose, therefore the expected duration of participation for 
each subject is approximately 24 months after the last dose. 
5.3 End of Trial Definition 
Trial end is defined as the point at which the last subject has completed the last visit. 
5.4 Trial Data Review 
An iSRC will evaluate all AEs on a pre-defined schedule in consultation with the PI. 
The roles and responsibilities of the iSRC will be described in the corresponding 
charter. 
5.5 Data and Safety Monitoring Board 
An independent DSMB (consisting of external independent vaccine experts) will 
review safety data (solicited and unsolicited AEs, SAEs and safety lab) on a regular 
basis and make recommendations about sequential enrolment of subjects into dose 
escalation groups. 
The DSMB will monitor safety during the trial and can meet ad hoc to review 
potentially related SAEs, AESIs, other unexpected related severe AEs or safety 
signals identified by the sponsor or designee. Trial dose administration will be 
temporally halted for the given dose level and resume after DSMB and competent 
authority approval. 
The roles and responsibilities of the DSMB will be described in the DSMB charter. 
5.6 Scientific Rationale for Trial Design 
The multi-cohort dose escalation trial design of CV-7202-104 is considered 
appropriate to investigate safety and immunogenicity of CV7202 in a FIH trial. The 
dose range, route of administration and regimen were initially selected based on non-
clinical studies which are further described in the IB [17]. A licensed vaccine, 

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Rabipur® was selected as an active control for safety, reactogenicity and 
immunogenicity. 
5.7 Justification for Dose 
The clinical dose range of 5-200 µg was justified based on data from two repeat dose 
toxicity studies (in rat and rabbit) and local reactogenicity and immunogenicity data 
from a pharmacology study in cynomolgus monkeys. 
The no observed adverse effect level (NOAEL) of CV7202 was calculated for both rat 
and rabbit. Rabbit was the most sensitive species. Doses intended for the phase 1 
study were evaluated using two different approaches based on the NOAEL in rabbit. 
Normalization of dose based on a direct mg/kg conversion of the NOAEL provided a 
human equivalent dose of 800 µg which is approximately 4-fold greater than the 
highest anticipated clinical dose of 200 µg. Allometric scaling provided a conservative 
maximum recommended starting dose of 26 µg which is approximately 5-fold the 
starting dose of 5 µg. Furthermore, toxicology studies evaluated animals which were 
administered 4 injections at weekly intervals while human subjects will receive a 
single injection or two injections at least 28 days apart. Doses up to 210 µg in 
cynomolgus monkeys were associated with only minimal to mild reactogenicity at the 
injection sites. 
Pharmacology data from a study of cynomolgus monkeys support the clinical dose 
range. After a single i.m. injection in cynomologus monkeys of 1 µg CV7202, VNTs 
above the threshold of protection were observed as early as Day 28 and were still 
detected six months later. By extrapolation, a dose of 1 µg in a monkey (0.3 µg/kg) 
would represent an equivalent dose of 5-15 µg in a human. Thus, it is possible that 
CV7202 will elicit an immune response in human subjects from the initially defined 
clinical starting dose of 5 µg. 
Based on the reactogenicity and immunogenicity results from the first 10 subjects 
vaccinated with CV7202 at the 5 µg dose level in the current trial, the dose ranges to 
be tested in the other groups have been lowered to 1 and 2 µg.  
5.8 Benefit-Risk Assessment 
5.8.1 Possible Risks and Adverse IMP Reactions 
No final clinical data for CV7202 are available to date. 
Evidence from non-clinical studies shows that CV7202 is well-tolerated in relevant 
animal species and no safety risks have been identified. 
The LNP-formulated RNActive® rabies vaccine (CV7202) for i.m. administration is 
being tested for the first time in humans. As with every vaccination and based on 
previous clinical experience with other RNActive® vaccines as well as preliminary 
data after administration of CV7202 to the first 10 subjects vaccinated with 5 µg of 
CV7202 in the current trial, local reactions, i.e. pain, redness, itching and swelling at 
the injection site, and systemic AEs, i.e. chills, fatigue, headache, fever, myalgia, 
arthralgia, nausea/vomiting and diarrhea, are expected side effects that typically 
resolve within 24 hours after the vaccination with or without corrective treatment with 
antipyretics [18, 19, 20, 21]. 

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As for every vaccine, the occurrence of allergic/anaphylactic reactions cannot be 
excluded and emergency equipment for the treatment of such reactions must be 
available at the trial site. These events are unexpected and constitute a potential 
important medical risk. So far, no allergic/anaphylactic reactions have been observed 
in the completed and ongoing clinical trials after repeated administration of 
protamine-formulated RNActive® vaccines, nor after administration of CV7202 to the 
first 10 subjects vaccinated with 5 µg of CV7202 in the current trial. 
During the very early stages of manufacture of CV7202, ampicillin is used. Although 
there is no evidence of residual ampicillin in the final investigational medicinal product 
(IMP), subjects with a previous class I allergic reaction to beta-lactam antibiotics 
should be excluded from vaccination with CV7202 as a measure of precaution. 
Developmental toxicity studies have not been performed for CV7202. No 
histopathological alterations in the reproductive organs were identified in the local 
tolerance or repeat-dose toxicology studies in rat or rabbit, and toxicologically 
relevant levels of RNA were not detected in reproductive organs in the biodistribution 
study. Therefore, the teratogenicity risk is deemed low. However, given that human 
data on pregnancies is not available, the teratogenic risk associated with CV7202 
administration cannot be ruled out at this moment. For this reason, inclusion of 
female subjects of childbearing potential requires use of a highly effective 
contraceptive measure from 2 weeks before the first administration of the test 
vaccine until 3 months following the last administration. 
5.8.2 Adverse Events of Special Interest 
Due to the theoretical possibility of non-specific immune stimulating properties of 
CV7202, it cannot be excluded that pre-existing potential immune mediated diseases 
(pIMDs) may be aggravated, become clinically apparent for the first time or triggered 
after vaccination with CV7202. Such reactions have been very rarely described after 
administration of other vaccines but the causal relationship between vaccination and 
the induction or aggravation of pIMDs is uncertain and is therefore a theoretical risk. 
These events are considered unexpected for CV7202. 
If suspected potential immune-mediated reactions should occur in a subject who 
received CV7202, a diagnostic workup should be performed by a specialist 
depending on the type of suspected reaction (e.g. endocrinologist for suspected 
autoimmune thyroiditis) and these conditions will be monitored and documented 
throughout the trial. AEs with a suspected pIMD etiology will be considered AESI. 
A list of AESIs will be closely followed throughout the trial (please see Appendix 10). 
5.8.3 Drug and Vaccines Interactions 
CV7202 has not been investigated in combination with other drugs or vaccines. 
Given the mechanism of action which relies on building up a protective immune 
response, it is expected that immunosuppressive drugs like steroids may inhibit the 
desired pharmacological effect of the induction of a specific immune response 
against the rabies virus G protein. Similarly, drugs that enhance the immune 
response like certain cytokines (interferon-α, interleukin 2) may increase the 
response to the vaccines which could theoretically result in increased efficacy but 
also in an increased risk of toxicity. 

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5.8.4 Precautions and Warnings 
CV7202 is an IMP. It should only be administered to subjects who have given written 
consent (see Appendix 2, Appendix 13, Appendix 15 and Appendix 16) to participate 
in a clinical trial for which a protocol has been approved by the sponsor, investigator, 
and any relevant authorities and ethics committees. 
CV7202 is intended strictly for i.m. injection by needle-syringe in the deltoid area 
(preferably in the non-dominant arm) and must not be injected subcutaneously, 
intradermally or intravenously. The instruction for injection described in the trial-
specific handling manual must be followed. An intravascular injection is highly 
unlikely at this site due the lack of larger blood vessels. However, a blood aspiration 
test should be performed prior to i.m. needle injection of CV7202 as a measure of 
precaution. 
Since there is a theoretical risk of anaphylactic reactions, the vaccine must only be 
administered if emergency equipment for the treatment of anaphylactic reactions 
(intravenous fluids, corticosteroids, H1 and H2 blocking agents, epinephrine, 
equipment for cardiopulmonary resuscitation) is readily available and subjects must 
remain under direct supervision of personnel trained in the treatment of these 
reactions for 4 hours following administration of the trial IMP. 
If anaphylaxis or severe hypersensitivity reactions occur following IMP administration, 
no further doses should be given. 
5.8.5 Recognition and Treatment of Possible Overdose and Adverse 
IMP Reactions 
No toxic effects are expected from current clinical and pre-clinical experience. 
Possible local reactions (pain) or systemic AEs (e.g. fever, headache, chills) can be 
treated symptomatically with physical measures, paracetamol or non-steroidal anti-
inflammatory drugs, at the investigator’s discretion. 
5.8.6 Benefit-Risk Conclusion 
In conclusion, CV7202 is expected to be safe at doses considered for the clinical trial. 
The expected adverse effects do not usually constitute important medical risks.  
Potential important medical risks associated with CV7202 have been identified based 
on the mechanism of action, and can be managed in a phase I setting should they 
occur. 

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6 Trial Population 
6.1 Inclusion Criteria 
Subjects must satisfy the following criteria at trial entry: 
1. Healthy male and female subjects aged 18 to 40 years inclusive. 
Healthy Subject is defined as an individual who is in good general health, not 
having any mental or physical disorder requiring regular or frequent medication. 
2. Expected to be compliant with protocol procedures and available for clinical 
follow-up through the last planned visit. 
3. Physical examination and laboratory results without clinically significant findings. 
4. Body Mass Index (BMI) ≥18.0 and ≤32.0 kg/m2. 
5. Females: At the time of screening, negative human chorionic gonadotropin (hCG) 
pregnancy test (serum) for women presumed to be of childbearing potential on 
the day of enrolment. On Day 1 (pre-vaccination): negative urine pregnancy test 
(hCG), (only required if the screening visit serum pregnancy test was performed 
more than 3 days before). 
6. Females of childbearing potential must use acceptable methods of birth control 
from 2 weeks before the first administration of the test vaccine until 3 months 
following the last administration. The following methods of birth control are 
acceptable when used consistently and correctly:  
 combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal or transdermal); 
 progestogen-only hormonal contraception associated with inhibition of 
ovulation (oral, injectable or implantable); 
 intrauterine devices (IUDs); 
 intrauterine hormone-releasing systems (IUSs); 
 bilateral tubal occlusion; 
 vasectomized partner; 
 sexual abstinence (periodic abstinence [e.g., calendar, ovulation, 
symptothermal and post-ovulation methods] and withdrawal are not 
acceptable). 
Refer to the Clinical Trial Facilitation Group (CTFG) recommendations on 
contraception and pregnancy testing for further details [23]. 
7. Males must use reliable forms of contraception (condom) from the moment of the 
first administration of the test vaccine until 3 months following the last administration 
and must refrain from sperm donation from the moment of the first administration 
of the test vaccine until 3 months after the last administration. 

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6.2 Exclusion Criteria 
Any trial subject who meets any of the following criteria will not qualify for entry into 
the trial: 
1. Use of any investigational or non-registered product (drug or vaccine) other than 
the trial vaccine within 4 weeks preceding the administration of the trial vaccine, 
or planned use during the trial period. 
2. Receipt of any other vaccines within 14 days (for inactivated vaccines) or 28 days 
(for live vaccines) prior to enrolment in this trial or planned receipt of any vaccine 
within 28 days of any trial vaccine administration. 
3. Receipt of any licensed or investigational rabies vaccine prior to the 
administration of the trial vaccine. 
4. Planning to travel to regions/countries for which rabies vaccinations are 
recommended or where high risk of infection exists according to travel 
recommendations by the German Society of Tropical Medicine and International 
Health during the trial and up to the end of the trial. 
5. Any treatment with immunosuppressants or other immune-modifying drugs within 
6 months prior to the administration of the trial vaccine or planned use during the 
trial, with the exception of inhaled and nasal steroids, or topically-applied steroids. 
6. Any medically diagnosed or suspected immunosuppressive or immunodeficient 
condition based on medical history and physical examination, including human 
immunodeficiency virus (HIV) infection, hepatitis B virus (HBV) infection and 
hepatitis C virus (HCV) infection. 
7. History of a potential immune mediated disease. 
8. Administration of immunoglobulins (Igs) and/or any blood products within the 
3 months preceding the administration of any dose of the trial vaccine. 
9.  Presence or evidence of significant acute or chronic, uncontrolled medical or 
psychiatric illness. 
10. Known allergy to any component of CV7202 such as type I allergy to beta-lactam 
antibiotics or Rabipur®. 
11. Evidence of current alcohol or drug abuse. 
12. History of any neurological disorders or seizures including Guillain-Barré 
syndrome (GBS), with the exception of febrile seizures during childhood. 
13. Foreseeable non-compliance with protocol as judged by the investigator. 
14. For females: Pregnancy or lactation. 
15. History of any life-threatening anaphylactic reactions. 
16. Subjects with impaired coagulation or any bleeding disorder in whom an i.m. 
injection or a blood draw is contraindicated. 
17. Known relatives of site research staff working on this trial. 

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6.3 Dose Modification / Vaccine Delay Recommendations 
After enrolment, subjects may encounter clinical circumstances that warrant a delay 
of trial dose administration. These situations are listed below: 
 Subjects with a clinically significant (≥ grade 2) active infection or other acute 
disease (as assessed by the investigator) or temperature >38.0°C (>100.4°F), 
within 3 days of intended trial vaccination. Further dose administration should be 
delayed until the active infection or other acute disease has recovered to ≤ grade 
1 or the subject is without temperature >38.0°C (>100.4°F) for at least 3 days. 
In the event that a subject meets a criterion for delay of vaccination, the subject may 
receive the trial dose once the window for delay has passed (Table 2.1) if clinically 
appropriate to vaccinate in the judgment of the investigator and the time windows of 
the protocol can be respected. 
There are also circumstances under which receipt of further vaccines is a 
contraindication in this trial (see section 5.1.2). If these reactions occur, the subject(s) 
must not receive additional vaccinations but is/are encouraged to continue in trial 
participation for safety reasons, including collection of safety blood samples. 
Immunogenicity assessments may be performed also, at the investigator’s discretion 
and if the subject agrees. 
6.4 Screen Failures 
The investigator must account for all subjects who sign an informed consent. If the 
subject is found to be not eligible at the screening visit (i.e. did not meet all inclusion 
criteria or did meet one or more exclusion criteria), the investigator should document 
this in the subject’s source data only. Re-screening is allowed if the reason for 
ineligibility is a transient event. 

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7 Discontinuation/Withdrawal Criteria 
Participation in the trial is strictly voluntary. A subject has the right to withdraw from 
the trial at any time and for any reason. The investigator has the right to withdraw a 
subject from further trial vaccine administration and/or the trial if this is considered in 
the subject’s best interest or is as a result of a protocol deviation.  
For discontinuations due to an AE, every effort should be made to document the 
outcome of the event. 
7.1 Discontinuation of Trial Vaccine Administration and/or Blood 
Sampling 
The primary reason for discontinuation of further administrations of CV7202 will be 
recorded in the subject’s electronic case report form (eCRF) according to the 
following categories: 
 The subject withdraws consent. The subject wishes to withdraw from the trial. The 
reason for withdrawal, if provided, should be recorded in the eCRF. 
Note: All attempts should be made to determine the underlying reason for the 
withdrawal and, where possible, the primary underlying reason should be recorded 
(i.e. withdrawal due to an AE should not be recorded in the “voluntary withdrawal” 
category). 
 AE (including known side effects of the test product). If discontinuation is due to 
an AE possibly related to CV7202, Rabipur® or the trial procedures, the subject 
must be followed-up by additional examinations according to the medical 
judgment of the investigator until the condition is resolved or the investigator 
deems further observations or examinations to be no longer medically indicated. 
 Change in the subject’s overall medical status prohibiting further participation. 
 Pregnancy (Appendix 12). Any subject who, despite the requirement for adequate 
contraception, becomes pregnant during the trial will not receive further trial 
vaccines. The site should maintain contact with the pregnant subject and 
complete a “Clinical Trial Pregnancy Form” as soon as possible. In addition, the 
subject should be followed-up until the birth of the child, or spontaneous or 
voluntary termination. When pregnancy outcome information becomes available, 
the information should be captured using the same form. The subject should be 
reported as an IMP discontinuation and the reason (e.g. pregnancy) should be 
given. 
 Trial terminated by the sponsor (in which case the minimum safety follow-up of 
one year would be performed). 
 Major protocol deviation. 
 Other. 
Note: The specific reasons should be recorded in the “specify” field of the eCRF. 
Subjects who will not receive further doses of CV7202 will be encouraged to continue 
participation until the end of the trial for safety assessments. Immunogenicity 
assessments may be performed at the investigator’s discretion, if the subject agrees. 

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7.2 Withdrawal from the Trial 
Withdrawal from the trial is recorded according to the following criteria: 
 Where continued participation jeopardizes the subject’s health, safety or rights. 
 The subject has experienced an AE that requires early termination because 
continued participation imposes an unacceptable risk to the subject’s health or the 
subject is unwilling to continue because of the AE. The reasons for not performing 
further safety or immunogenicity assessments should be documented. 
 The subject did not return to the trial site and multiple attempts (at least 3) to 
contact the subject were unsuccessful (lost to follow-up). 
 The subject wishes to withdraw from the trial. The reason for withdrawal, if 
provided, should be recorded. 
Note: All attempts should be made to determine the underlying reason for the 
withdrawal and, where possible, the primary underlying reason should be recorded 
(i.e. withdrawal due to an AE should not be recorded in the “voluntary withdrawal” 
category). 
Any subject who prematurely terminates participation and who has received at least 
one vaccination will undergo the same procedures as for the final visit, unless such 
procedures are considered to pose unacceptable risk to the subject. 
Discontinued or withdrawn subjects will not be replaced, except in the case of 
dropouts occurring before Visit 4 for the first 4 subjects from Groups 3 or 4, unless 
the affected subjects have experienced any AE fulfilling the stopping criteria and the 
DSMB does not approve the replacement (section 5.1.2). 
7.3 Trial Termination 
The sponsor reserves the right to terminate the trial at any time. Possible reasons for 
trial termination are: 
 Safety reasons: the incidence of AEs in this or any other trial using a related IMP 
indicating a potential health risk for the subjects. 
 New scientific knowledge becomes known that makes the objectives of the trial no 
longer feasible/valid. 
 The trial site is unlikely to be able to recruit sufficient subjects within the agreed 
time frame. 
 The trial site does not respond to trial management requests. 
 Repeated protocol deviations. 
 Unsafe or unethical practices. 
 Administrative decision. 
Following a trial termination decision, the investigator must contact all subjects within 
a time period set by the sponsor. All trial materials must be collected and relevant 
documentation completed to the greatest extent possible. 

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7.4 Lost to Follow-Up 
A minimum of 3 attempts to contact subjects who have not returned for the final visit 
or discontinuation visit should be made and documented. If a subject is lost to follow-
up before resolution of related SAEs or AEs indicating potential immune mediated 
disease, the sponsor may consider further attempts to contact the subject in order to 
collect follow-up safety information. 

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8 Clinical Trial Material Management 
The following sections describe the procedures for clinical trial material management 
for protocol CV-7202-104. Refer to the protocol CV-7202-104 Handling Manual for 
further information on CV7202 and to the product information leaflet [24] for 
additional information concerning Rabipur®. 
8.1 Trial Vaccine and Formulation 
The IMP is composed of the API, CV7202: RABV-G encoding mRNA, and 
The IMP is provided as a sterile solution in a 2 ml 
glass vial with rubber stopper closure. 
Mixing of CV7202 and 0.9 % sodium chloride (NaCl) to produce dosing solutions for 
i.m. injection will occur at the local pharmacy according to the handling protocol 
provided by CureVac. The volume to be administered is 0.5 ml for Group 2, 0.1 ml for 
Group 3 and 0.2 ml for Group 4, corresponding to dose levels of 5 µg, 1 µg and 2 µg 
mRNA, respectively. 
8.2 Control Vaccine 
Rabipur® (GSK Vaccines GmbH, Marburg, Germany) is a licensed rabies vaccine* 
(inactivated, strain Flury LEP) ≥2.5 IU / 1.0 ml reconstituted dose. 
This vaccine contains residues of polygeline, chicken proteins (e.g., ovalbumin), 
human serum albumin, and may contain traces of neomycin, chlortetracycline and 
amphotericin B. 
* Produced on purified chick embryo cells (PCEC). 
8.3 Route of Administration 
Injections will be performed i.m. by needle in the deltoid area (non-dominant arm), in 
all groups. 
8.4 Trial Groups 
The subjects will be distributed among the different groups to receive CV7202 or 
Rabipur® (Table 8.1). 

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Table 8.1 
Protocol CV-7202-104 Dose regimen 
 
Trial Product 
Composition 
Dosing 
Day 1 
Day 8 
Day 29 
N 
N 
N 
Group 1 
Rabipur® 
N/A 
10 
10 
10 
Group 2* 
CV7202 
5 µg mRNA 
10 
N/A 
N/A 
Group 3 
1 µg mRNA 
16 
8 
 
Group 3a** 
Group 4 
2 µg mRNA 
16 
8 
 
Group 4a** 
Total CV7202 
 
 
42 
 
16 
* Note that enrolment in Group 2 was already completed at the time this protocol amendment was 
issued. 
** ‘a’ groups are a subset consisting of 8 subjects of Groups 3 and 4 scheduled to receive a first dose 
on Day 1 and a second dose on Day 29.  
8.5 Method of Trial Vaccine Assignment 
This trial is non-randomized. Eight vaccinated subjects in Groups 3 and 4 will receive 
two doses of CV7202 and the remaining 8 subjects in these groups will receive one 
dose of CV7202. 
8.6 Blinding 
This trial is open label. 
8.7 Trial Vaccine and Supplies Accountability 
It is the responsibility of the investigator to ensure that current and accurate records 
of trial supplies received, stored and dispensed at the site are maintained using 
appropriate forms according to applicable regulations and guidelines. The trial 
supplies must be stored under the recommended storage conditions, locked with 
restricted access (refer to the Handling Manual). Authorized personnel must dispense 
the vaccine at the trial site and in accordance with the protocol and applicable 
regulations and guidelines. 
A dispensing log for CV7202 must be kept up-to-date at the trial site with the 
following information: 
 Dates and quantities of CV7202 received from CureVac. 
 Unique subject identifier. 
 Date and quantity of trial vaccine dispensed to each subject. 
 Initials of the person preparing the dose. 
 Initials of the person administering the vaccine. 
These accountability forms must be readily available for inspections and are open to 
regulatory inspection at any time. 
8.8 Vaccine Compliance 
The investigator will record all injections of trial vaccine (CV7202 and Rabipur®) given 
to the subject in the electronic eCRF. 

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8.9 Concomitant Therapy and Vaccines 
Concomitant medication and vaccines must be recorded in the subject’s eCRF. 
If post-exposure vaccination for rabies is needed, the subject should be discontinued 
from receiving a further trial dose, but followed-up for safety assessments. 
For additional information, refer to section 6.2. 
8.10 Therapy leading to elimination 
If a trial subject requires therapy listed as an exclusion criterion in section 6.2 and 
which cannot be delayed, discontinuation would be considered to ensure integrity of 
the trial data, following individual case review. Medications taken for prophylaxis (i.e. 
intended to prevent the onset of symptoms following vaccination) are not allowed. 
8.11 Treatment after the End of the Trial 
No post-trial care will be provided. 

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9 Trial Assessments and Procedures 
The following sections describe the trial procedures and data to be collected. 
Additional trial-related information is provided in section 12, Appendix 1 to Appendix 
17. 
9.1 Adverse Events 
Definitions and procedures for recording, evaluating, follow-up, and reporting of AEs 
are provided in Appendix 11. The intensity of AEs will be graded in the following 
manner: 
Absent: 
 Grade 0 
 No AE 
Mild: 
 Grade 1 
 An event that is easily tolerated by the subject, 
causing minimal discomfort and not interfering with 
everyday activities. 
Moderate: 
 Grade 2 
 An event that causes sufficient discomfort to interfere 
with normal everyday activities. 
Severe: 
 Grade 3 
 An event that prevents normal everyday activities. An 
AE that is assessed as severe should not be confused 
with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be 
assessed as severe. 
Solicited AEs will be collected on the day of vaccination and the 7 subsequent days 
(Days 1-8) and the intensity grading will be applied (Table 9.1 and Table 9.2). By 
definition, all local solicited symptoms are considered related to vaccination. 
Unsolicited AEs will be collected on the day of vaccination and the 28 subsequent 
days (Days 1-29). 
Table 9.1 
Intensity Grading for Solicited Local AEs (Days 1 to 8) 
AE 
Grade 
Definition 
Pain at 
injection 
site* 
0 
Absent 
1 
Does not interfere with activity 
2 
Interferes with activity and/or repeated use of non-narcotic pain 
reliever >24 hours 
3 
Prevents daily activity and/or repeated use of narcotic pain reliever 
Redness* 
0 
≤2.5 cm 
1 
2.5 – 5 cm 
2 
5.1 – 10 cm 
3 
>10 cm 
Swelling* 
0 
≤2.5 cm 
1 
2.5 – 5 cm and does not interfere with activity 
2 
5.1 – 10 cm or interferes with activity 
3 
>10 cm or prevents daily activity 
Itching 
0 
Absent 
1 
Mild, no interference with normal activity  
2 
Moderate, some interference with normal activity 
3 
Significant, prevents normal activity 
*FDA toxicity grading scale [25]. 

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Table 9.2 
Intensity Grading* for Solicited Systemic AEs (Days 1 to 8) 
AE 
Grade 
Definition 
Fever 
0 
<38°C 
1 
≥38 – 38.4°C 
2 
≥38.5 – 38.9°C 
3 
≥39°C 
Headache 
0 
Absent 
1 
Mild, no interference with normal activity 
2 
Moderate, some interference with normal activity and/or 
repeated use of non-narcotic pain reliever >24 hours 
3 
Significant; any use of narcotic pain reliever and/or prevents 
daily activity 
Fatigue 
0 
Absent 
1 
Mild, no interference with normal activity  
2 
Moderate, some interference with normal activity 
3 
Significant, prevents normal activity 
Chills  
0 
Absent 
1 
Mild, no interference with normal activity 
2 
Moderate, some interference with normal activity 
3 
Severe, prevents normal activity 
Myalgia 
0 
Absent  
1 
Mild, no interference with normal activity  
2 
Moderate, some interference with normal activity 
3 
Significant, prevents normal activity 
Arthralgia 
0 
Absent  
1 
Mild, no interference with normal activity  
2 
Moderate, some interference with normal activity 
3 
Significant, prevents normal activity 
Nausea/ 
Vomiting 
0 
Absent  
1 
Mild, no interference with activity and/or 1 – 2 episodes/ 24 
hours 
2 
Moderate, some interference with activity and/or >2 episodes/ 
24 hours 
3 
Severe, prevents daily activity, requires outpatient i.v. hydration 
Diarrhea 
0 
Absent 
1 
2 – 3 loose stools or <400 g/24 hours 
2 
4 – 5 stools or 400 – 800 g/24 hours 
3 
6 or more watery stools or >800 g/24 hours or requires 
outpatient IV hydration 
*FDA toxicity grading scale [25]; i.v. = Intravenous. 
Laboratory data will be graded according with the FDA toxicity grading scale [25] and 
the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0 [26]. 
These guidelines however are dependent upon institutional normal parameters. 
Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate. 
AEs with a suspected immune mediated disease etiology will be considered AESIs. 
The list of AESI is provided in (Appendix 10). 

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Definitions and Procedures for Recording, Evaluating, Follow-up, and Reporting of 
AEs are provided in Appendix 11. 
9.2 Safety Assessments 
The following safety assessments apply to all subjects in Groups 1 to 4: 
All vaccinations will be administered on an outpatient basis. All subjects will be 
monitored for 4 hours following administration of the trial IMP. Vital signs must be 
within normal ranges or have returned to pre-vaccination levels (pre-vaccination 
values ± 15% or no clinically relevant deviation from pre-vaccination values) for the 
subject to be discharged. 
All subjects will undergo a vaccination site reactogenicity assessment (injection site 
pain, redness, swelling and itching) at 1 hour post vaccination on the day of 
vaccination (Day 1, Day 8 [Rabipur® Dose 2] and Day 29 [Rabipur® and Groups 3a 
and 4a]) and 1 or 2 days after each vaccination (Day 2 or 3, Day 10 [Rabipur® 
Dose 2] and Day 30 or 31 [Rabipur® and Groups 3a and 4a]). Note that Days 3 and 
31 were planned in the original protocol and only apply to subjects in Groups 1 and 2 
who were already enrolled and vaccinated before this protocol amendment was 
issued. Days 2 and 30 apply to all other subjects. For those subjects, a phone call will 
be performed to collect safety information 2 days after each vaccination. 
Local reactions at 1 hour post-vaccination will be assessed on an intensity scale of 
absent, mild, moderate and severe. The trial personnel will record these in the eCRF. 
Diary cards will be distributed to all subjects and used to collect solicited local 
(injection site pain, redness, swelling and itching) and systemic (fever, 
nausea/vomiting, diarrhea, headache, fatigue, myalgia and arthralgia) AEs on the 
day of vaccination and the 7 subsequent days (Days 1 to 8, Day 8 to 15 [Rabipur® 
Dose 2] and Days 29 to 36). Local reactions and systemic events will be assessed on 
an intensity scale of absent, mild, moderate and severe. The diary card will be 
reviewed on Day 2 or 3, 8, 10, 15, 29, 30 or 31, 36, 43 and 57. In case of related 
grade 3 solicited or unsolicited AEs reported for more than 1 day on the diary card, 
the subject will be interrogated to establish the total duration of the AE and this 
information will be recorded in the medical file. Unsolicited AEs occurring on the day 
of vaccination (Day 1, Day 8 and Day 29) and for the following 28 days will be 
recorded by the subject on the diary card. 
The occurrence of AEs (serious and non-serious) will be assessed by non-directive 
questioning of the subject at each visit. AEs volunteered by the subject during or 
between visits as subject diary card entries or detected through observation, physical 
examination, laboratory test, or other assessments during the entire trial, will be 
documented. Subjects will be instructed that they must immediately report any AEs 
with serious symptoms, subjective complaints or objective changes in their well-being 
to the investigator or the clinic personnel, regardless of the perceived relationship 
between the event and the test vaccine. 
SAEs, MAAEs and AEs leading to trial or vaccine withdrawal will be collected up to 
12 months after the last dose administration. After Visit 15 (Month 12), only SAEs 
and MAAEs that according to the investigator are considered to be related to study 
vaccination will be collected. 
Intercurrent medical conditions and AESIs will be collected throughout the trial. 

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Clinical laboratory testing for safety evaluations are provided in Appendix 6. 
Definitions and procedures for recording, evaluating, follow-up and reporting of AEs 
are provided in Appendix 11. 
9.3 Immunogenicity Assessments 
The following immunogenicity assessments will be made: 
Rabies-specific serum VNTs will be measured using the WHO-recommended rapid 
fluorescent foci inhibition test (RFFIT) before and after vaccination on Days 1, 8, 15, 
29, 36, 43, 57, 91, and 6, 12, 18 and 24 months post-last dose. 
The percentages of vaccine recipients with VNTs ≥0.5 IU/ml (WHO-recommended 
threshold correlating with protective immune responses) will be determined for each 
trial group. An antibody titer of 0.5 IU/ml serum is viewed as a surrogate of protection 
and defines seroconversion [26]. GMTs by treatment group will be calculated based 
on the VNTs on Days 1, 8, 15, 29, 36, 43, 57, 91, and 6, 12, 18 and 24 months post-
last dose. VNTs assessments will be performed in a GCP-compliant laboratory. 
Note that VNTs assessments at 18 and 24 months after the last vaccination will only 
be performed in subjects with detectable RABV-G-specific IgG at 6 months after the 
last vaccination or Day 91 if the Month 6 blood sample is not available. 
RABV-G-specific IgM, IgG and IgA serum antibody levels will be measured by 
enzyme-linked immunosorbent assay (ELISA) on Days 1, 8, 15, 29, 36, 43, 57, 91, 
and 6 and 12 months post-last dose. In addition, RABV-G-specific IgG serum 
antibody levels will be measured at 18 and 24 months after the last vaccination in 
subjects with detectable RABV-G-specific IgG at 6 months after the last vaccination 
or Day 91 if the Month 6 blood sample is not available. 
Additional immune-related effects will be assessed by exploratory analyses in 
peripheral blood samples, including measurements of serum cytokines, chemokines, 
and other soluble factors. These analytes include but are not limited to chemokine 
(C-X-C motif) ligand (CXCL)10, chemokine (CC motif) ligand (CCL)3, interleukin-6 
(IL-6), tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) on Days 1 (at pre-
vaccination and 4 hours post-vaccination), 2 or 3 and 8 after each vaccination. Gene 
expression changes in peripheral blood will be determined by transcriptome profiling 
on Days 1 (at pre-vaccination), 2 or 3 and 8 after each vaccination. Cytokine 
assessments and transcriptome profiling will only be performed in the first 5 subjects 
in Group 2 (on Day 3) and all subjects in Groups 3 and 4 (on Day 2). Note that Day 3 
post-vaccination was planned in the original protocol and only applies to subjects in 
Group 2 who were already enrolled and vaccinated before this protocol amendment 
was issued. Day 2 post-vaccination applies to all other subjects.  
RABV-G-specific CD4+ and CD8+ T-cell responses will be determined by intracellular 
cytokine staining after 6-hour incubation of PBMCs in the presence of overlapping 
peptides covering the open reading frame of RABV-G on Days 1, 8, and 36. The 
groups will be tested in their entirety at Day 91 and 6 and 12 months post-last dose if 
there is a significant increase in T-cell response at Day 8 or 36 compared to baseline. 
RABV-G-specific circulating B cells will be determined in PBMC samples by enzyme-
linked immunospot (ELISpot) assay after short-term cell culture on Days 1, 8 and 36. 
The groups will be tested in their entirety at Day 91 and 6 and 12 months post-last 
dose if there is a significant increase in B-cell response at Day 8 or 36 compared to 

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baseline. Lymphocyte phenotyping will be performed by conventional flow cytometry 
or cytometry by time of flight (CyTOF). 
The humoral immune response against RABV-G will be further characterized by 
immune receptor sequencing of peripheral B cells, on Days 1, 8, 29, 36, 57, 91, and 
6 and 12 months post-last dose in a subset of subjects; and measurement of 
antibody affinity and avidity, measurement of VNTs against additional heterologous 
lyssavirus strains and identification of epitopes recognized by RABV-G-specific 
antibodies, on Days 1, 15, 43, and 12 months post last dose, on selected samples 
with VNT >0.5 IU/ml. 
Additional exploratory testing, not defined in the objectives/endpoints, may be 
performed to further characterize the vaccine or immune response, including the 
development or improvement of tests related to the disease or the trial vaccines that 
will allow more reliable measurement of the response to the trial vaccines. 
9.4 Trial Procedures 
For each procedure, subjects are to be assessed by the same investigator or site 
personnel whenever possible. Refer to the Schedule of Activities (Table 2.1). 
9.4.1 Visit 1 (Pre-screening Visit, Days -90 to -1) 
Pre-screening visit activities can occur between 90 and 1 days prior to vaccination. 
 Signed informed consent must be obtained prior to the subject entering into the 
trial, and before any protocol-directed procedures are performed. 
The following procedures will be performed during the pre-screening visit: 
 Collection of demographic information. 
 Vital signs check (body temperature, pulse, blood pressure). 
 Record medical history, including details of treatments for re-occurring conditions. 
 Review of eligibility criteria. See sections 6.1 and 6.2 
 Safety assessments (SAEs, intercurrent medical conditions, AEs leading to trial 
withdrawal, AESIs and MAAEs). 
 Blood draw (section 9.5) for: 
 Thyroid-stimulating hormone (TSH), thyroid antibodies, antinuclear antibody 
(ANA) (~3 ml). Blood drawn at the pre-screening visit will be kept for 
retrospective measurement of TSH, thyroid antibodies and ANA following the 
occurrence of clinical autoimmune events (other autoantibodies might be 
investigated as well depending on the clinical autoimmune event).  
9.4.2 Visit 2 (Screening Visit, Days -30 to -1) 
Screening visit activities can occur between 30 and 1 day prior to vaccination and 
may be performed on the same day as the Pre-Screening visit. The following 
procedures will be performed during the screening visit: 
 Review of eligibility criteria. See sections 6.1 and 6.2. 
 Serum pregnancy test (hCG) (~2 ml) for female subjects of childbearing potential. 

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 Physical examination (including weight, height, and general condition). 
 12-lead electrocardiogram (ECG). 
 Assessment of concomitant medications/vaccinations. 
 Safety assessments (SAEs, intercurrent medical conditions, AEs leading to trial 
withdrawal, AESIs and MAAEs). 
 Blood draw (section 9.5) for safety laboratory (~9 ml). 
9.4.3 Visit 3 (Vaccination Dose 1 CV7202 or Dose 1 Rabipur®, Day 1) 
The following procedures will be performed during Visit 3: 
 Review of eligibility criteria (sections 6.1 and 6.2). 
 Review of criteria for vaccine delay (section 6.3). 
 Urine pregnancy test for female subjects of childbearing potential, unless the 
serum pregnancy test was performed less than 3 days before. 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), PBMCs* for CMI 
(~60 ml), cytokine assessment (~6 ml at pre-vaccination and ~6 ml at 4 hours 
post-vaccination [CV7202 groups only]), transcriptome profiling (~10 ml at pre-
vaccination [CV7202 groups only]), immune receptor sequencing (~5 ml). 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 3 and 4. 
 Vaccination (Dose 1 CV7202 or Dose 1 Rabipur®). 
 Post-injection vaccination site reactogenicity assessment after 1 hour for all 
subjects. Note that all subjects need to remain at the site for 4 hours after 
vaccination for safety monitoring. Vital signs will be then re-checked and have to 
be within normal ranges or have returned to pre-vaccination levels for the subject 
to be discharged. 
 Subjects will be issued with diary cards to record solicited AEs occurring on the 
day of vaccination and the following 7 days. Unsolicited AEs occurring on the day 
of vaccination and for the following 28 days will also be recorded by the subject 
on the diary card. Subjects will be instructed on how to complete the diaries. 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
9.4.4 Visit 4 (Day 2 or 3) 
The following procedures will be performed during Visit 4: 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 

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 Post-injection vaccination site reactogenicity assessment. 
 Diary card review and reminder. 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity* – cytokine assessment (~6 ml), transcriptome profiling 
(~10 ml) only for CV7202 groups. 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 
It should be noted that for subjects enrolled in the trial before Protocol Amendment 1 
became effective, Visit 4 occurred on Day 3 as planned in the original protocol 
9.4.5 Phone call (Day 3) 
A phone call should be performed on Day 3 for the CV7202 groups only to collect 
the following safety information: 
 Any solicited AEs (including duration in case of grade 3 AEs), unsolicited AEs 
(including duration in case of grade 3 AEs), SAEs, intercurrent medical conditions, 
AEs leading to trial or vaccine withdrawal, AESIs and MAAEs experienced by the 
subject or any concomitant medications and vaccinations taken by the subject. 
9.4.6 Visit 5 (Vaccination Dose 2 Rabipur®, Day 8) 
The following procedures will be performed during Visit 5: 
Group 1 only: Vaccination (Dose 2 Rabipur®): 
 Review of criteria for vaccine delay (section 6.3). 
 Urine pregnancy test for female subjects of childbearing potential. 
 Vaccination (Dose 2 Rabipur®). 
 Post-injection vaccination site reactogenicity assessment after 1 hour and then 
subjects will be discharged if the vital signs are within normal ranges or have 
returned to pre-vaccination levels. 
 Diary collection for solicited AEs occurring up to Day 8 (Dose 1 Rabipur®). 
 Subjects will be issued with diary cards to record solicited AEs occurring on the 
day of vaccination (Dose 2 Rabipur®) and the following 7 days. Unsolicited AEs 
occurring on the day of vaccination up to Day 29 will also be recorded by the 
subject on the diary card. Subjects will be instructed on how to complete the 
diaries. 
Groups 2-4 only: 
 Diary review for solicited AEs occurring up to Day 8 (Dose 1 CV7202). 
 Diary card returned to the subjects for collection of unsolicited AEs up to Day 29 
(Dose 1 CV7202). 

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All subjects: 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), PBMCs* for CMI (~40 
ml), cytokine assessment (~6 ml [CV7202 groups only]), transcriptome 
profiling (~10 ml [CV7202 groups only]), immune receptor sequencing (~5 ml). 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
9.4.7 Visit 6 (Day 10) 
The following procedures will be performed during Visit 6 for Group 1 only: 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Post-injection vaccination site reactogenicity assessment after 2 days in subjects 
having received Rabipur®dose 2. 
 Diary card review and reminder. 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
9.4.8 Visit 7 (Day 15) 
The following procedures will be performed during Visit 7: 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Diary card reminder/review for unsolicited AEs occurring up to Day 29 (Dose 1 
CV7202). 
 Group 1 only: Diary review for solicited AEs occurring up to Day 15 (Dose 2 
Rabipur®). 
 Group 1 only: Diary card returned to the subjects for collection of unsolicited AEs 
up to Day 36 (Dose 2 Rabipur®). 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml). 

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 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml). 
9.4.9 Visit 8 (Vaccination Dose 2 CV7202* or Dose 3 Rabipur®, 
Day 29) 
The following procedures will be performed during Visit 8: 
 Review of criteria for vaccine delay (for Groups 1, 3a and 4a section 6.3). 
 Urine pregnancy test for female subjects of childbearing potential. 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml) and immune receptor 
sequencing (~5 ml) in all subjects; cytokine assessment (~6 ml at pre-
vaccination and ~6 ml at 4 hours post-vaccination [CV7202 groups only]) and 
transcriptome profiling (~10 ml at pre-vaccination [CV7202 groups only]) in 
subjects from Groups 3a and 4a who received a second dose of CV7202. 
* The second dose will be administered to 8 subjects of each group (Groups 3a to 
4a). 
 Vaccination (Dose 2 CV7202 or Dose 3 Rabipur®). 
 Post-injection vaccination site reactogenicity assessment after 1 hour for all 
subjects who received a vaccine. Note that all subjects need to remain at the site 
for 4 hours after vaccination for safety monitoring. Vital signs will be then re-
checked and have to be within normal ranges or have returned to pre-vaccination 
levels for the subject to be discharged. 
 Diary review and collection for unsolicited AEs occurring up to Day 29 (Dose 1 
CV7202 and Rabipur®) and up to Day 36 (Dose 2 Rabipur®). 
 Subjects will be issued with diary cards to record solicited AEs occurring on the 
day of vaccination with Dose 2 CV7202 or Dose 3 Rabipur® and the following 7 
days. Unsolicited AEs occurring on the day of vaccination and for the following 28 
days will also be recorded by the subject on the diary card. 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
9.4.10 
Visit 9 (Day 30 or 31**) 
The following procedures will be performed during Visit 9 only for Group 1 and 
subjects who received CV7202 Dose 2 (Groups 3a and 4a): 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Post-injection vaccination site reactogenicity assessment after 1 or 2 days* for all 
subjects who received Dose 2 CV7202 or Dose 3 Rabipur®. 
 Diary card review and reminder. 

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 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml) 
 Immunogenicity* – cytokine assessment (~6 ml), transcriptome profiling 
(~10 ml) only for CV7202 groups. 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 
** For some subjects already vaccinated with Rabipur® before this protocol 
amendment was issued, Visit 9 occurred on Day 31 as planned in the original 
protocol. For other subjects, the visit should occur on Day 30. 
9.4.11 
Phone call (Day 31) 
A phone call should be performed on Day 31 for the CV7202 3a and 4a groups only 
to collect the following safety information: 
 Any solicited AEs (including duration in case of grade 3 AEs), unsolicited AEs 
(including duration in case of grade 3 AEs), SAEs, intercurrent medical conditions, 
AEs leading to trial or vaccine withdrawal, AESIs and MAAEs experienced by the 
subject or any concomitant medications and vaccinations taken by the subject. 
9.4.12 
Visit 10 (Day 36) 
The following procedures will be performed during Visit 10: 
 Physical examination (including weight and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Diary review for solicited AEs occurring up to Day 36 (Dose 2 CV7202, Dose 3 
Rabipur®). 
 Diary card returned to the subjects for collection of unsolicited AEs up to Day 57 
(Dose 2 CV7202, Dose 3 Rabipur®). 
 Safety assessments (solicited AEs, unsolicited AEs, SAEs, intercurrent medical 
conditions, AEs leading to trial or vaccine withdrawal, AESIs and MAAEs, 
concomitant medications and vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), PBMCs* for CMI 
(~40 ml) and immune receptor sequencing (~5 ml); cytokine assessment 
(~6 ml [CV7202 groups only]) and transcriptome profiling (~10 ml [CV7202 
groups only]). 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 

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9.4.13 
Visit 11 (Day 43) 
The following procedures will be performed during Visit 11: 
 Diary card review and reminder. 
 Safety assessments (unsolicited AEs, SAEs, intercurrent medical conditions, AEs 
leading to trial or vaccine withdrawal, AESIs and MAAEs, concomitant 
medications and vaccinations). 
 Blood draw for: 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml). 
9.4.14 
Visit 12 (Day 57) 
The following procedures will be performed during Visit 12: 
 Physical examination (including weight and general condition). 
 Diary review and collection for unsolicited AEs occurring up to Day 57 (Dose 2 
CV7202; Dose 3 Rabipur®). 
 Safety assessments (unsolicited AEs, SAEs, intercurrent medical conditions, AEs 
leading to trial or vaccine withdrawal, AESIs and MAAEs, concomitant 
medications and vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), immune receptor 
sequencing (~5 ml). 
9.4.15 
Visit 13 (Day 91) 
The following procedures will be performed during Visit 13: 
 Physical examination (including weight and general condition). 
 Safety assessments (SAEs, intercurrent medical conditions, AEs leading to trial or 
vaccine withdrawal, AESIs and MAAEs, concomitant medications and 
vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), PBMCs* for CMI (~40 
ml), immune receptor sequencing (5 ml). 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 

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9.4.16 
Visit 14 (Month 6: Day 181 [1-dose groups]/ Day 209 
[2-dose groups and Group 1 (Rabipur®)] 
9.4.16.1 
Visit 14 
The following procedures will be performed during Visit 14: 
 Safety assessments (SAEs, intercurrent medical conditions, AEs leading to trial or 
vaccine withdrawal, AESIs and MAAEs, concomitant medications and 
vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml). 
 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), PBMCs* for CMI (~40 
ml), immune receptor sequencing (5 ml). 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 
In case Visit 14 cannot take place on site due to the public health emergency related 
to COVID-19, safety information should be collected via a phone call within the 
protocol-allowed time interval for Visit 14 (±14 days).  
9.4.16.2 
Optional Visit 14A 
Visit 14A may be conducted only in case Visit 14 was conducted as a phone call, and 
when restrictive measures related to COVID-19 no longer prevent site visits, and the 
window of Visit 14 has expired. Visit 14A allows the trial procedures, including the blood 
draws for safety and immunogenicity testing, to occur during a widened visit window 
starting the day after the expiry of the original visit window and lasting up to 3 months 
after the original projected visit date (+15-90 days). In that case, all procedures as 
described in Section 9.4.16.1 for Visit 14, including blood sampling for safety and 
immunogenicity assessments, should be performed at Visit 14A. 
Also, in case Visit 14 was conducted on site but not all procedures could be performed, 
Visit 14A should be scheduled on site within the protocol-allowed time interval for 
Visit 14A (+15-90 days). 
9.4.17 
Visit 15 (Month 12: Day 365 [1-dose groups]/ Day 393 
[2-dose groups and Group 1 (Rabipur®)] 
9.4.17.1 
Visit 15 
The following activities will be performed during Visit 15: 
 Physical examination (including weight, and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Safety assessments (SAEs, intercurrent medical conditions, AEs leading to trial or 
vaccine withdrawal, AESIs and MAAEs, concomitant medications and 
vaccinations). 
 Blood draw for: 
 Safety laboratory (~9 ml) (section 9.5.1). 

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 Immunogenicity – VNTs (~18 ml), IgM/IgG/IgA (~6 ml), PBMCs* for CMI 
(~40 ml), immune receptor sequencing (5 ml) (section 9.5.3). 
* PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all 
subjects in Groups 1, 3 and 4. 
In case Visit 15 cannot take place on site due to the public health emergency related 
to COVID-19, safety information should be collected via a phone call within the 
protocol-allowed time interval for Visit 15 (±30 days). 
9.4.17.2 
Optional Visit 15A 
Visit 15A may be conducted only in case Visit 15 was conducted as a phone call, and 
when restrictive measures related to COVID-19 no longer prevent site visits, and the 
window of Visit 15 has expired. Visit 15A allows the trial procedures, including the blood 
draws for safety and immunogenicity testing, to occur during a widened visit window 
starting the day after the expiry of the original visit window and lasting up to 3 months 
after the original projected visit date (+31-90 days). In that case, all procedures as 
described in Section 9.4.17.1 for Visit 15, including and blood sampling for safety and 
immunogenicity assessments, should be performed at Visit 15A.  
Also, in case Visit 15 was conducted on site but not all procedures could be performed, 
Visit 15A should be scheduled on site within the protocol-allowed time interval for 
Visit 15A (+31-90 days). 
If no blood sampling could be performed at Visit 15 and 15A, the end-of-trial blood 
sample for safety assessment may be performed at Visit 17 (Month 24: Day 729). 
9.4.18 
Visit 16 (Month 18: Day 547) 
9.4.18.1 
Visit 16 
The following activities will be performed during Visit 16: 
 Safety assessments (SAEs related to study vaccination, MAAEs related to study 
vaccination, intercurrent medical conditions, AESIs and concomitant medications 
and vaccinations). 
 Blood draw for immunogenicity (only in subjects with detectable RABV-G-specific 
IgG at 6 months after the last vaccination or Day 91 if the Month 6 blood sample 
is not available) – VNTs (~18 ml), IgG (~6 ml) (section 9.5.3). 
In case Visit 16 cannot take place on site due to the public health emergency related 
to COVID-19, safety information should be collected via a phone call within the 
protocol-allowed time interval for Visit 16 (±30 days).  
9.4.18.2 
Optional Visit 16A 
Visit 16A may be conducted only in case Visit 16 was conducted as a phone call, and 
when restrictive measures related to COVID-19 no longer prevent site visits, and the 
window of Visit 16 has expired. Visit 16A allows the trial procedures, including the blood 
draws for immunogenicity testing, to occur during a widened visit window starting the 
day after the expiry of the original visit window and lasting up to 3 months after the 
original projected visit date (+31-90 days). In that case, all procedures as described in 

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Section 9.4.16.1 for Visit 16, including blood sampling for immunogenicity assessment, 
should be performed at Visit 16A.  
Also, in case Visit 16 was conducted on site but not all procedures could be performed, 
Visit 16A should be scheduled on site within the protocol-allowed time interval for 
Visit 16A (+31-90 days). 
9.4.19 
Visit 17 (Trial End) (Month 24: Day 729) 
9.4.19.1 
Visit 17 
During the final trial visit, the following activities will be performed: 
 Physical examination (including weight, and general condition) and vital signs 
check (body temperature, pulse, blood pressure). 
 Safety assessments (SAEs related to study vaccination, MAAEs related to study 
vaccination, intercurrent medical conditions, AESIs and concomitant medications 
and vaccinations). 
 Blood draw for immunogenicity (only in subjects with detectable RABV-G-specific 
IgG at 6 months after the last vaccination or Day 91 if the Month 6 blood sample 
is not available) – VNTs (~18 ml), IgG (~6 ml) (section 9.5.3). 
If the subject withdraws prior to the end of the trial, trial end visit procedures should 
be performed. 
Subjects should be asked whether they would agree to be contacted for participation 
in a follow-up trial. 
In case Visit 17 cannot take place on site due to the public health emergency related 
to COVID-19, safety information should be collected via a phone call within the 
protocol-allowed time interval for Visit 17 (±30 days).  
9.4.19.2 
Optional Visit 17A 
Visit 17A may be conducted only in case Visit 17 was conducted as a phone call, and 
when restrictive measures related to COVID-19 no longer prevent site visits, and the 
window of Visit 17 has expired. Visit 17A allows the trial procedures, including the blood 
draws for immunogenicity testing, to occur during a widened visit window starting the 
day after the expiry of the original visit window and lasting up to 6 months after the 
original projected visit date (+31-180 days). In that case, all procedures as described 
in Section 9.4.19.1 for Visit 17, including physical examination, measurement of vital 
signs and blood sampling for immunogenicity assessment, should be performed at 
Visit 17A.  
Also, in case Visit 17 was conducted on site but not all procedures could be performed, 
Visit 17A should be scheduled on site within the protocol-allowed time interval for 
Visit 17A (+31-180 days). 
If no blood sampling could be performed at Visits 15 and 15A, the end-of-trial blood 
sample for safety assessment may be performed at Visit 17 or 17A. 

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9.5 Blood Draws 
Blood draws will occur at 16 visits and prior to vaccination (Visits 3, 5 and 8). In 
addition to the pre-vaccination blood sample at Visits 3 and 8, a blood sample at 
4 hours post-vaccination will be taken for cytokine assessment in the CV7202 
groups. Maximal volume taken per subject over the duration of the trial is ~809 ml 
(Table 9.3). 
PBMCs will be taken for a subset of the first 5 subjects in Group 2 and all subjects in 
Groups 1, 3 and 4. 
In case a site visit is not possible due to the public health emergency related to 
COVID-19, the blood sample for immunogenicity assessments at Months 6, 12, 18 
and 24 should be performed at Visits 14A, 15A, 16A and 17A, respectively, only in 
case restrictive measures related to COVID-19 no longer prevent site visits (refer to 
Sections 9.4.16 to 9.4.19 for details).  
Clinical laboratory tests are described in Appendix 6. 

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Table 9.3 
Timing and Maximum Volumes of Blood Draws 
Visit 
Procedure 
V1 
V2 
V3 
V4 
V5 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14/ 
V14A§ 
V15/ 
V15A§ 
V16/ 
V16A§ 
V17/ 
V17A § 
∑ 
Pregnancy Test (ml)* 
Serum hCG 
- 
2 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
2 
Safety (ml) 
Safety Laboratory 
- 
9 
9 
9 
9 
9 
9 
9 
9 
- 
9 
9 
9 
9 
- 
- 
108 
TSH, Thyroid 
Antibodies, ANA 
3 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
- 
3 
Immunogenicity (ml) 
VNT 
- 
- 
18 
- 
18 
18 
18 
- 
18 
18 
18 
18 
18 
18 
18‡ 
18‡ 
216 
IgM/IgG/IgA 
- 
- 
6 
- 
6 
6 
6 
- 
6 
6 
6 
6 
6 
6 
6‡ 
6‡ 
72 
Cell-mediated 
Immunity 
- 
- 
60 
- 
40 
- 
- 
- 
40 
- 
- 
40 
40 
40 
- 
- 
260 
Cytokines** 
- 
- 
12† 
6 
6 
- 
12† 
6 
6 
- 
- 
- 
- 
- 
- 
- 
48 
Transcriptome 
Profiling** 
- 
- 
10 
10 
10 
- 
10 
10 
10 
- 
- 
- 
- 
- 
- 
- 
60 
Immune Receptor 
Sequencing 
- 
- 
5 
- 
5 
- 
5 
- 
5 
- 
5 
5 
5 
5 
- 
- 
40 
Total 
3 
11 
120 
25 
94 
33 
60 
25 
94 
24 
38 
78 
78 
78 
24 
24 
809 
∑ = Sum; No blood draw at Visit 6. 
* For female subjects of childbearing potential.  
** Cytokine and transcriptome profiling assessments will only be performed for subjects in the CV7202 groups. 
§ The optional Visits 14A, 15A, 16A and 17A may only take place in case the respective visit could not be conducted as described in the protocol. If no 
blood sampling could be performed at Visits 15 and 15A, the end-of-trial blood sample for safety assessment may be performed at Visit 17. 
† Two blood samples will be taken on the day of vaccination, i.e. at pre-vaccination and 4 hours post-vaccination. 
‡ At Month 18 and Month 24, VNTs and IgG assessments will be performed only in subjects with detectable RABV-G-specific IgG at 6 months after the 
last vaccination or Day 91 if the Month 6 blood sample is not available. 

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9.5.1 Safety Lab (Visits 2 to 5, 7 to 10 and 12 to 15) 
Safety laboratory assessments for hematology (complete blood count, including 
differential and platelets) and biochemistry will be performed as outlined in Appendix 
6. Coagulation (activated partial thromboplastin time [aPTT]), and prothrombin 
time/international normalized ratio [INR]) will be performed at the following time 
points: Screening, Days 1, 3 and 31. 
The approximate volume taken for safety laboratory is ~9 ml per visit. Blood will be 
taken for the safety laboratory at 12 visits. 
In case a site visit is not possible due to the public health emergency related to 
COVID-19, the blood sample for safety assessment at Month 6 and Month 12 should 
be collected at Visit 14A and Visit 15A, respectively, only in case restrictive measures 
related to COVID-19 no longer prevent site visits (refer to Section 9.4.16 and 9.4.17 
for details). If no blood sampling could be performed at Visits 15 and 15A (Month 12), 
the end-of-trial sample for safety assessment may be performed at Visit 17 (Month 
24). 
9.5.2 Thyroid-stimulating Hormone, Thyroid Antibodies, Antinuclear 
Antibodies (Pre-screening Visit) 
The approximate volume taken for TSH, thyroid antibodies, ANA is ~3 ml per visit. 
Blood will be taken for TSH, thyroid antibodies, ANA at 1 visit. Blood drawn at the pre-
screening visit will be kept for retrospective measurement of TSH, thyroid antibodies 
and ANA following the occurrence of clinical autoimmune events (other 
autoantibodies might be investigated as well depending on the clinical autoimmune 
event). 
9.5.3 Immunogenicity (Visits 3 to 5, 7 to 17) 
The approximate volumes taken for immunogenicity testing are: 
 VNTs (serum) (~18 ml). Blood will be taken at 12 visits. 
 IgM/ IgG ELISA (serum) (~6 ml). Blood will be taken at 12 visits. 
 Cell-mediated immune response and leukocyte phenotyping of PBMCs (~60 ml at 
baseline and ~40 ml at subsequent visits) – PBMCs will be taken for the first 5 
subjects in Group 2 and all subjects in Groups 3 and 4. In addition, all 10 subjects 
receiving Rabipur® will be included. Blood will be taken at 6 visits. 
 Cytokine assessment (serum) (~6 ml) – for the subjects in the CV7202 groups 
providing PBMCs. A total of 7 (or 8 for subjects receiving 2 doses of CV7202) 
blood samples will be taken at 6 visits. 
 Transcriptome profiling (PBMCs) (~10 ml) – for the subjects in the CV7202 groups 
providing PBMCs for cell-mediated immune response and leukocyte phenotyping. 
Blood will be taken at 6 visits. 
 Immune receptor sequencing (PAXgene DNA) (~5 ml). Blood will be taken at 
8 visits. 

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In case a site visit is not possible due to the public health emergency related to 
COVID-19, the blood sample for immunogenicity assessments should be collected at 
Visits A, only in case restrictive measures related to COVID-19 no longer prevent site 
visits (refer to Sections 9.4.16 to 9.4.19 for details). 

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10 Statistical Considerations 
Due to the exploratory nature of this trial only descriptive statistics will be used, no 
confirmatory statistical inference will be performed. 
10.1 Sample Size Determination 
No statistically-based sample size estimation was performed. 
10.2 Populations for Analyses 
Safety set: This is the subset of subjects, who have received at least one dose of the 
candidate rabies mRNA vaccine CV7202 or the active control Rabipur® and for whom 
any post-Day 1 safety data are available. The statement that a subject had no AEs 
(on the Adverse Event eCRF) constitutes a valid safety assessment. The analysis of 
safety will be performed on this population. 
Full-analysis (FA) set: This is the subset of the Safety Set with subjects who have 
the baseline sample and at least one additional blood sample available for VNT 
analysis. This analysis set is the primary analysis set for all immunogenicity 
objectives. 
Per protocol (PP) set: This is defined as a subset of the FA set as follows: 
1. PP1 = Subjects enrolled in Group 1 (Rabipur®) and Groups 2 to 4 who have received 
at least 1 administration of the trial product (including those to be selected for the 
second vaccination), have completed the Day 57 visit and for whom baseline 
through Day 57 immunological results (at least rabies VNTs) are available. 
2.  PP2 = Defined as a subset of PP1 comprised of subjects who have received two 
administrations of the trial product, have completed the Day 91 visit and for whom 
baseline through Day 91 immunological results (at least rabies VNTs) are available. 
Any subject for whom substantive protocol deviations are documented will be 
excluded from the PP set. The following pre-defined major protocol deviations will 
lead to the exclusion from the PP set: 
 Any deviation of the Inclusion/Exclusion criteria. 
 Any trial subject that requires therapy listed as an exclusion criterion in section 6.2. 
 Any trial subject that has not received the trial product on the scheduled date. 
 Any trial subject for whom the immunological sample has been taken outside of 
the planned visit window. 
 Pre-existing RABV-G specific immune response. 
Further subgroup analyses may be defined and specified in the statistical analysis 
plan (SAP). 

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10.3 Statistical Analyses 
10.3.1 
General Considerations 
All data obtained in this trial and documented in the eCRF will be listed and 
summarized with sample statistics or frequency tables as appropriate. In all tables, 
listings and figures the dose groups will be reported from the lowest to the highest 
dose, with the ‘a’ groups as separate columns. 
A statistical analysis plan (SAP) will be prepared and finalized at the latest prior to 
database lock for the interim analysis. This document will provide further details 
regarding the definition of analysis variables and analysis methodology to address all 
trial objectives and the handling of missing data. 
This trial is designed as an exploratory phase I trial with no confirmatory proof of 
hypotheses. 
10.3.2 
Demographic, Medical History, Prior Medication and 
other Baseline Characteristics 
Demographic characteristics, medical history, prior medication and other baseline 
data will be listed and summarized using descriptive statistics for numerical data and 
contingency tables for categorical data. Medical history and prior medication will only 
be listed. 
10.3.3 
Study vaccine 
The administrations of CV7202 will be listed. 
10.3.4 
Concomitant medication and Vaccinations 
Concomitant medication/vaccination and significant non-drug therapies after the start 
of study treatment will be listed and summarized by Anatomical Therapeutic Chemical 
(ATC) term in contingency tables. 
10.3.5 
Safety Analyses 
The following safety and reactogenicity data will be summarized descriptively: vital 
signs, and vaccination site reactogenicity assessment. 
The occurrence of solicited local and systemic AEs reported on the day of each 
vaccination and the 7 subsequent days and unsolicited AEs reported on the day of 
each vaccination and the 28 subsequent days will be presented. 
The safety measurements will include: 
1. AEs (type, intensity, frequency and relationship to vaccination), i.e. incidence and 
severity of AEs for both solicited local and systemic events (occurring on the day of 
vaccination and the 7 subsequent days) and unsolicited events (occurring on the 
day of vaccination and the 28 subsequent days). 
2. SAEs, MAAEs and AEs leading to trial or vaccine withdrawal up to 12 months post 
last dose. After Visit 15 (Month 12), only SAEs and MAAEs that according to the 

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investigator are considered to be related to study vaccination will be collected. 
3. Intercurrent medical conditions and AESIs throughout the trial. 
4. Local reactogenicity assessment of injection site in all subjects. 
Further, the incidence of AEs will be summarized in frequency tables by Medical 
Dictionary for Regulatory Activities (MedDRA) terms (system organ class [SOC] and 
preferred term [PT]). AEs that are reported as related to the test vaccine will be 
considered trial vaccine-related; missing classifications concerning trial vaccine 
relationship will also be considered trial vaccine-related. 
Concomitant medications and vaccinations will be coded and summarized. Physical 
examination data will be listed. 
Clinical laboratory test results with values below/above the reference range will be 
counted. 
10.3.6 
Immunogenicity Analyses (Secondary/Exploratory 
Objectives) 
Baseline is defined as Day 1 (Visit 3; before vaccination). 
Immune response will be assessed using the following parameters: 
1. Number and percentage of subjects having VNTs ≥0.5 IU/ml on Days 1, 15, 43, and 
12, 18 and 24 months post last dose. 
2. Individual functional antibody titers, GMTs and range of titers in sera collected on 
Days 1, 8, 15, 29, 36, 43, 57, 91, and 6, 12, 18 and 24 months post-last dose. 
Further immunogenicity assessments will be based on VNTs, RABV-G-specific IgG, 
IgM and IgA serum antibodies, RABV-G-specific T cells and B cells in peripheral 
blood and other immunogenicity-related parameters such as cytokine serum 
concentrations, including but not limited to CXCL10, CCL3, IL-6, TNF -α and IFN-γ, 
gene expression changes, antibody affinity and avidity, throughout the duration of the 
trial. Results will be summarized in tables, figures and supported by subject level 
listings. 
10.3.7 
Missing data 
Analysis of vaccination variables will be done on a valid case basis, i.e., for missing 
observations, no imputation for missing data, such as last observation carried forward 
(LOCF), will be applied. For safety data, some missing or partially missing variables 
will be imputed as follows:  
• 
For start date: 
• 
If the AE start date year value is missing, the date uncertainty is too high to 
impute a rational date. Therefore, if the AE year value is missing, the 
imputed AE start date is set to missing. 
• 
If the AE start date year value is less than the treatment start date year 
value, the AE started before treatment. Therefore: 
- 
If the AE year is lower than the treatment year and the AE month is 
missing, the imputed AE start date is set to the mid-year point (i.e., 
01JULYYYY). 

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- 
If the AE year is lower than the treatment year and the AE month is 
not missing, the imputed AE start date is set to the mid-month point 
(i.e., 15MONYYYY). 
• 
If the AE start date year value is greater than the treatment start date year 
value, the AE started after treatment. Therefore, if the AE year is greater 
than the treatment year and the AE month is missing, the imputed AE start 
date is set to the year start point (i.e., 01JANYYYY). 
• 
For resolution date: 
• 
If date of resolution is completely missing, it is assumed that it resolved at 
the date of the end of the AE assessment period. 
• 
If year is present, it is assumed that it resolved on 31 December of that 
year (i.e., 31DECYYYY), or at the end of the AE assessment period if 
earlier. 
• 
If year and month are present, it is assumed that it resolved on the last day 
of that month, or at the end of the AE assessment period if earlier. 
No other safety variables will be imputed. In case the number of missing/partial dates 
for solicited local AEs, solicited systemic AEs or individual solicited AEs is higher than 
expected for the analysis of durations (in days), a sensitivity analysis will be 
conducted to assess the impact on the primary endpoint. 
10.3.8 
Interim analyses 
One or more interim analyses may be performed for this trial. The data will be 
cleaned for all subjects. The analyses will be based on a data snapshot. Analyses will 
be performed on the safety set only. No decision-making is planned for the interim 
analyses and no adjustments for the trial are planned based on the results. As this 
trial is of exploratory nature and no inferential statistics are planned, no adjustment for 
multiple testing will be done.  

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11 References 
1. ICH Guidelines. Available at: http://www.ich.org/products/guidelines.html. 
Accessed 12 December 2017. 
2. Human rabies: 2016 updates and call for data. WHO Weekly epidemiological 
record. 7 2017, 92, 77-88. Available at: 
http://apps.who.int/iris/bitstream/10665/254622/2/WER9207.pdf?ua=1. Accessed 
12 December 2017. 
3. Malerczyk C Rabies pre-exposure vaccination in rabies endemic countries. J 
Vaccines Vaccin 2012; 3 (7): doi: 10.4172/2157-7560.1000e114. 
4. Strategic Advisory Group of Experts (SAGE) Working Group on rabies vaccines 
and rabies immunoglobulins (established July 2016): Available at: 
http://www.who.int/immunization/policy/sage/sage_wg_rabies_jul2016/en/. 
Accessed 12 December 2017. 
5. Human rabies prevention – United States, 2008. Available at: 
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5703a1.htm. Accessed 12 
December 2017. 
6. Infectious diseases related to travel. Available at: 
https://wwwnc.cdc.gov/travel/yellowbook/2018/infectious-diseases-related-to-
travel/rabies. Accessed 12 December 2017. 
7. Piyaphanee W, Kittitrakul C, Lawpoolsri S, Gautret P, Kashino W, Tangakanakul 
W, et al. Risk of potentially rabid animal exposure among foreign travelers in 
southeast Asia. PLoS Negl Trop Dis. 2012; 6(9): e1852. 
8. Gautret P and Parola P. Rabies vaccination for international travelers. Vaccine. 
2012; 30 (2): 126-133. 
9. Rabies factsheet. Available at: 
http://www.who.int/mediacentre/factsheets/fs099/en/. Accessed 12 December 
2017. 
10. Ravish HS, Srikanth J, Narayana DH, Annadani R Vijayashankar V and Undi M. 
Pre-exposure prophylaxis against rabies in children – safety of purified chick 
embryo cell rabies vaccine (Vaxirab N) when administered by intradermal route. 
Human Vacc Immunother 2013; 9(9): 1910-1913. 
11. Sorrentino S. Human extracellular ribonucleases: multiplicity, molecular diversity 
and catalytic properties of the major RNase types. Cell. Mol. Life Sci. CMLS; 
1998; 54(8): 785–794. 
12. Reichmuth AM, Oberli MA, Jaklenec A, Langer R and Blankschtein D. mRNA 
vaccine delivery using lipid nanoparticles. Ther. Deliv. 2016; 7(5): 319–334. 
13. Lutz J, Laazzaro S, Habbeddine M, Schmidt KE, Baumhof P, Mui BL et al. 
Unmodified mRNA in LNPs constitutes a competitive technology for prophylactic 
vaccines. npj Vaccines 2017: 2(29), doi:10.1038/s41541-017-0032-6 (2017). 

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14. Petsch B, Schnee M, Vogel AB, Lange E, Hoffmann B, Voss D, et al. Protective 
efficacy of in vitro synthesized, specific mRNA vaccines against influenza A virus 
infection. Nat Biotechnol. 2012 Dec;30(12):1210-6. 
15. Alberer M, Gnad-Vogt U, Hong HS, Mehr KT, Backert L, Finak G, Gottardo R, 
Bica MA, Garofano A, Koch SD, Fotin-Mleczek M, Hoerr I, Clemens R, von 
Sonnenburg F. Safety and immunogenicity of a mRNA rabies vaccine in healthy 
adults: an open-label, non-randomised, prospective, FIH phase 1 clinical trial. 
Lancet 2017; 390(10101): 1511-152. 
16. Reichmuth AM, Oberli MA, Jeklenec A, Langer R and Blankschtein D. mRNA 
vaccine delivery using lipid nanoparticles. Ther Deliv. 2016; 7(5):319-34. 
17. Investigator’s Brochure CV7202 V1.0. 
18. Alberer M, Gnad-Vogt U, Hong HS, Mehr KT, Backert L, Finak G, et al. Safety and 
immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-
randomised, prospective, first-in-human phase 1 clinical trial. Lancet. 
2017;390(10101):1511-1520. 
19. Kübler H, Scheel B, Gnad-Vogt U, et al. Self-adjuvanted mRNA vaccination in 
advanced prostate cancer patients: a first-in-man phase I/IIa study. Journal for 
Immunotherapy of Cancer. 2015;3:26. doi:10.1186/s40425-015-0068-y. 
20. Hong HS, Koch SD, Scheel B, et al. Distinct transcriptional changes in non-small 
cell lung cancer patients associated with multi-antigenic RNActive® CV9201 
immunotherapy. Oncoimmunology. 2016;5(12):e1249560. 
doi:10.1080/2162402X.2016.1249560. 
21. Rausch S, Schwentner C, Stenzl A, Bedke J. mRNA vaccine CV9103 and 
CV9104 for the treatment of prostate cancer. Hum Vaccin Immunother. 
2014;10(11):3146-52. 
22. Guideline on strategies to identify and mitigate risks for 5 first-in-human and early 
clinical trials with investigational medicinal products. Available at: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/201
7/07/WC500232186.pdf. Accessed 12 December 2017. 
23. Clinical Trial Facilitation Group (CTFG) Recommendations related to 
contraception and pregnancy testing in clinical trials, September 2014. Available 
at: http://www.hma.eu/fileadmin/dateien/Human_Medicines/01-
About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf 
24. Rabipur® - Product Information (2010). 
25. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in 
Preventive Vaccine Clinical Trials (September 2007) Available at: 
https://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceReg
ulatoryInformation/Guidances/Vaccines/ucm091977.pdf. Accessed 12 December 
2017. Accessed 12 December 2017. 
26. Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. National 
Cancer Institute. Published: November 27, 2017. Available at: 

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https://ctep.cancer.gov/protocoldevelopment/electronic_applications/docs/CTCAE
_v5_Quick_Reference_8.5x11.pdf (Accessed on March 09, 2018). 
27. Rabies vaccines WHO position paper. WHO Weekly epidemiological record, No. 
49/50, 2007, 82:425-436. Available at: 
http://www.who.int/wer/2007/wer8249_50.pdf. Accessed 12 December 2017. 

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12 Appendices 
The following appendices are provided below: 
Appendix 1 
Investigator Signature Page ............................................................... 65 
Appendix 2 
Responsibilities of the Investigator ..................................................... 67 
Appendix 3 
Protocol Approvers ............................................................................. 69 
Appendix 4 
Emergency Procedures ...................................................................... 70 
Appendix 5 
Abbreviations and Trademarks ........................................................... 71 
Appendix 6 
Clinical Laboratory Tests .................................................................... 73 
Appendix 7 
Trial Governance Considerations ....................................................... 74 
Appendix 8 
Protocol changes ................................................................................ 76 
Appendix 9 
Disclosure........................................................................................... 77 
Appendix 10 Adverse Events of Special Interest ..................................................... 78 
Appendix 11 Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting ................................................. 80 
Appendix 12 Contraceptive Guidance and Collection of Pregnancy Information .... 86 
Appendix 13 Data Management and Quality Control .............................................. 88 
Appendix 14 Protocol Deviations ............................................................................ 90 
Appendix 15 Ethics and Regulations ....................................................................... 91 
Appendix 16 Biological Samples and Record Retention ......................................... 92 
Appendix 17 Protocol Amendment History .............................................................. 93 
 

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Appendix 1 Investigator Signature Page 
Protocol Title: 
A non-randomized, open label, controlled, dose-escalation, 
phase I clinical trial to evaluate the safety, reactogenicity and 
immunogenicity of one or two administrations candidate 
rabies mRNA vaccine CV7202 in healthy adult subjects 
Protocol Number: CV-7202-104 
Confidentiality and GCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and I will 
conduct the trial as described in compliance with this protocol, GCP, and relevant ICH 
guidelines. 
I understand that all information obtained during the conduct of the trial with regard to 
the subjects’ state of health will be regarded as confidential. No subjects’ names will 
be disclosed. All subjects will be identified by assigned numbers on all eCRFs and 
laboratory samples. Clinical information may be reviewed by the sponsor or designee 
or regulatory agencies. Agreement must be obtained from the subject before 
disclosure of subject information to a third party. 
Institution 

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Protocol Title: 
A non-randomized, open label, controlled, dose-escalation, 
phase I clinical trial to evaluate the safety, reactogenicity and 
immunogenicity of one or two administrations candidate 
rabies mRNA vaccine CV7202 in healthy adult subjects 
Protocol Number: CV-7202-104 
Confidentiality and GCP Compliance Statement 
I, the undersigned, have reviewed this protocol, including appendices and I will 
conduct the trial as described in compliance with this protocol, GCP, and relevant ICH 
guidelines. 
I understand that all information obtained during the conduct of the trial with regard to 
the subjects’ state of health will be regarded as confidential. No subjects’ names will 
be disclosed. All subjects will be identified by assigned numbers on all eCRFs and 
laboratory samples. Clinical information may be reviewed by the sponsor or designee 
or regulatory agencies. Agreement must be obtained from the subject before 
disclosure of subject information to a third party. 
 

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Appendix 2 Responsibilities of the Investigator 
Clinical research studies sponsored by the sponsor are subject to ICH GCP and all 
the applicable local laws and regulations. 
The investigator agrees to assume the following responsibilities: 
1. Conduct the trial in accordance with the protocol ICH-E6 (R2), and all the 
applicable local laws and regulations. 
2. Personally conduct or supervise the staff who will assist with the protocol. 
3. Ensure that trial related procedures including trial specific (non-routine/non-
standard panel) screening assessments are NOT performed on potential subjects, 
prior to the receipt of written approval from relevant governing bodies/authorities. 
4. Ensure that all colleagues and employees assisting in the conduct of the trial are 
informed of these obligations. 
5. Secure prior approval of the trial and any changes by an appropriate IEC and 
competent authority. 
6. Ensure that the IEC will be responsible for initial review, continuing review, and 
approval of the protocol. 
7. Ensure that requirements for informed consent, as outlined in ICH-E6 (R2) 4.8 and 
local regulations, are met. 
8. Obtain valid informed consent from each subject and document the date of 
consent in the subject’s medical chart. Valid informed consent is the most current 
version approved by the IEC. Each informed consent form should contain a 
subject authorization section that describes the uses and disclosures of a 
subject’s personal information (including personal health information) that will take 
place in connection with the trial. If an informed consent form does not include 
such a subject authorization, then the investigator must obtain a separate subject 
authorization form from each subject. 
9. Prepare and maintain adequate case histories of all persons entered into the trial, 
including eCRFs, hospital records, laboratory results, etc., and maintain these 
data for a minimum of 2 years following notification by the sponsor that all 
investigations have been discontinued or that the regulatory authority has 
approved the marketing application. The investigator should contact and receive 
written approval from the sponsor before disposing of any such documents. 
10. Ensure that clinical data is entered into the eCRFs within 24 hours of the visit day 
during the staggered enrolment phase and within 5 days post-visit for all other 
visits. In case a subject forgets to bring the diary card to a review visit, the subject 
will be requested to provide a fax-copy, photo-copy or scan of the diary to the site 
staff as soon as possible after the visit. 
11.  Allow possible inspection and copying by the regulatory authority of GCP-specified 
source documents. 
12. Maintain current records of the receipt, administration, and disposition of sponsor-
supplied vaccines, and return all unused sponsor-supplied vaccines to the 
sponsor. 

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13.  In the event of an SAE, AESI or overdose notify 
within 24 hours via 
SAE/AESI/overdose report form signed by the investigator. 
14.  Review and provide a signature as approval of the content of the clinical study 
report. 

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Appendix 3 Protocol Approvers 
Protocol Title: 
A non-randomized, open label, controlled, dose-escalation, 
phase I clinical trial to evaluate the safety, reactogenicity and 
immunogenicity of one or two administrations of candidate 
rabies mRNA vaccine CV7202 in healthy adult subjects 
Protocol Number: 
CV-7202-104 
Protocol Approvers 
 

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Appendix 4 Emergency Procedures 
During and after subjects’ participation in this trial, the investigator or institution 
should ensure that adequate medical care is provided to subjects who present with 
any AEs, including clinically significant laboratory values related to the administration 
of trial IMP. The investigator or institution should inform subjects when medical care is 
needed for intercurrent illness(es) of which the investigator becomes aware. 
Emergency equipment for the immediate treatment of allergic/anaphylactic reactions 
(steroids, H1, H2 antihistaminergic agents, intravenous fluids, oxygen, epinephrine 
and equipment for cardiopulmonary resuscitation) must be available at all times for 
the treatment of these events, and trained personnel must be present at all times 
while subjects are being monitored after vaccination. 
The trial site should have immediate access to equipment and appropriately qualified 
staff for resuscitating and stabilizing subjects in an acute emergency (such as cardiac 
emergencies, anaphylaxis, cytokine release syndrome, convulsions, hypotension), 
and ready availability of intensive care unit and other hospital facilities. 

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Appendix 5 Abbreviations and Trademarks 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ANA 
Antinuclear antibody 
API 
Active Pharmaceutical Ingredient 
aPTT 
Activated partial thromboplastin time 
BCR 
B-cell receptor 
CA 
Competent authorities 
CCL 
Chemokine (CC motif) ligand 
CDC 
Centers for Disease Control and Prevention (US) 
CMI 
Cell-mediated immunity 
CRO 
Contract research organization 
CXCL 
Chemokine (C-X-C motif) ligand 
DSMB 
Data and Safety Monitoring Board 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
ELISA 
Enzyme-linked immunosorbent assay 
FA 
Full analysis 
FDA 
US Food and Drug Administration 
FIH 
First-in-human 
GCP 
Good Clinical Practice 
GMT 
Geometric mean titer 
hCG 
Human chorionic gonadotropin 
IB 
Investigator’s brochure 
ICH 
International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use 
i.d. 
Intradermal 
IEC 
Independent Ethics Committee 
IFN-γ 
Interferon-gamma 
Ig 
Immunoglobulin 
IL 
Interleukin 
i.m. 
Intramuscular 
IMP 
Investigational medicinal product 
INR 
International normalized ratio 
iSRC 
Internal safety review committee 
IUD 
Intrauterine device 
IUS 
Intrauterine systems 
LNP 
Lipid nanoparticles 
MAAE 
Medically-attended adverse event 
mRNA 
Messenger ribonucleic acid 
NHP 
Non-human primate 
NOAEL 
No-observed-adverse-effect level 
PBMC 
Peripheral blood mononuclear cell 
PI 
Principal Investigator 
pIMD 
potential Immune Mediated Disease 
PP 
Per protocol 
RABV-G 
Rabies virus glycoprotein 

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RNA 
Ribonucleic acid 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SOP 
Standard operating procedure 
TNF-α 
Tumor necrosis factor-alpha 
TSH 
Thyroid stimulating hormone 
VNT 
Virus-neutralizing antibody titer 
WHO 
World Health Organization 
 

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Appendix 6 Clinical Laboratory Tests 
The tests detailed in Table 12.1 will be performed by the local laboratory. 
Additional tests may be performed at any time during the trial as determined 
necessary by the investigator or required by local regulations. 
Table 12.1 Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Complete blood count including differential and platelets 
Biochemistry 
Magnesium, creatinine, albumin and lactate dehydrogenase 
(LDH), C-reactive protein (CRP), gamma glutamyl transferase 
(GGT), blood urea nitrogen (BUN), bilirubin, calcium, alkaline 
phosphatase, sodium, potassium, total protein, glutamic 
oxaloacetic transaminase (GOT)/ aspartate aminotransferase 
(ASAT), glutamic pyruvic transaminase (GPT)/alanine 
aminotransferase (ALAT) 
Coagulation 
Prothrombin time/international normalized ratio (INR), 
activated partial thromboplastin time (aPTT) 
Serum Pregnancy Tests 
Human chorionic gonadotropin (hCG) 
The investigator must document his review of each laboratory safety report, by 
signing and dating the report. 

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Appendix 7 Trial Governance Considerations 
CureVac AG is the sponsor of this trial. A contract research organization (CRO) will 
organize the performance of this trial. 
Table 12.2 List of Names and Addresses 

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Appendix 8 Protocol changes 
Amendments to this trial protocol may be made following the procedures specified by 
local laws and regulations. Substantial amendments to this trial protocol may be 
implemented only if the approval of the competent authority / authorities [CA(s)] and a 
favorable opinion of the Independent Ethics Committee(s) [IEC(s)] have been 
obtained. 
Substantial amendments to the conduct of the clinical trial may arise from changes to 
the protocol or from new information relating to the scientific documents in support of 
the trial. Amendments to the trial are regarded as “substantial” where they are likely to 
have a significant impact on: 
 The safety, physical health and mental integrity of the subjects. 
 The scientific value of the trial. 
 The conduct or management of the trial. 
 The quality or safety of any IMP used in the trial. 
If a new event occurs related to the conduct of the trial or the development of the 
investigational medicinal product, which may affect the safety of the subjects, the 
sponsor and the investigator will take appropriate safety measures to protect the 
subjects against any immediate hazard. The sponsor will immediately inform the 
CA(s) and IEC(s) of the new events and the measures taken. 

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Appendix 9 Disclosure 
Publication of results 
The original data and the data otherwise obtained during the trial under this trial 
protocol will become the property of the sponsor. Any publication or scientific 
communication related to this trial can only take place once the manuscript has been 
reviewed by the sponsor, and once a written agreement between the sponsor and the 
investigator has been reached. 
The sponsor will follow all applicable regulations and legal obligations in regards to 
disclosure of data. 
Clinical trial report 
After completion of the trial, the results will be tabulated, evaluated and issued as a 
complete final clinical trial report according to the ICH-E3 Note for guidance on 
structure and content of clinical trial reports. 
The sponsor will send a summary of this clinical trial report to the EC and CA within 1 
year after the end of the trial defined as the last subject’s last follow up visit. 

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Appendix 10 
Adverse Events of Special Interest 
Current list of AESIs  
Gastrointestinal disorders:  
o Celiac disease  
o Crohn's disease  
o Ulcerative colitis  
o Ulcerative proctitis  
Liver disorders:  
o Autoimmune cholangitis  
o Autoimmune hepatitis  
o Primary biliary cirrhosis  
o Primary sclerosing cholangitis  
Metabolic diseases:  
o Addison's disease  
o Autoimmune thyroiditis (including Hashimoto thyroiditis)  
o Diabetes mellitus type I  
o Grave's or Basedow's disease  
Musculoskeletal disorders:  
o Antisynthetase syndrome  
o Dermatomyositis  
o Juvenile chronic arthritis (including Still's disease)  
o Mixed connective tissue disorder  
o Polymyalgia rheumatic  
o Polymyositis  
o Psoriatic arthropathy  
o Relapsing polychondritis  
o Rheumatoid arthritis  
o Scleroderma, including diffuse systemic form and CREST syndrome  
o Spondyloarthritis, including ankylosing spondylitis, reactive arthritis (Reiter's Syndrome) and 
undifferentiated spondyloarthritis  
o Systemic lupus erythematosus  
o Systemic sclerosis  
Neuro-inflammatory disorders:  
o Acute disseminated encephalomyelitis, including site specific variants (e.g., non-infectious 
encephalitis, encephalomyelitis, myelitis, myeloradiculomyelitis)  
o Cranial nerve disorders, including paralyses/paresis (e.g., Bell's palsy)  
o Guillain-Barré syndrome, including Miller Fisher syndrome and other variants  
o Immune-mediated peripheral neuropathies and plexopathies, including chronic 
inflammatory 
demyelinating 
polyneuropathy, 
multifocal 
motor 
neuropathy 
and 
polyneuropathies associated with monoclonal gammopathy  
o Multiple sclerosis  
o Narcolepsy  
o Optic neuritis  
o Transverse Myelitis  

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Current list of AESIs (cont.) 
Skin disorders:  
o Alopecia areata  
o Autoimmune bullous skin diseases, including pemphigus, pemphigoid and dermatitis 
herpetiformis  
o Cutaneous lupus erythematosus  
o Erythema nodosum  
o Morphoea  
o Lichen planus  
o Psoriasis  
o Sweet's syndrome  
o Vitiligo  
Vasculitides:  
o Large vessels vasculitis including: giant cell arteritis such as Takayasu's arteritis and 
temporal arteritis  
o Medium sized and/or small vessels vasculitis including: polyarteritis nodosa, Kawasaki's 
disease, microscopic polyangiitis, Wegener's granulomatosis, Churg-Strauss syndrome 
(allergic granulomatous angiitis), Buerger's disease thromboangiitis obliterans, necrotizing 
vasculitis and anti-neutrophil cytoplasmic antibody (ANCA) positive vasculitis (type 
unspecified), Henoch- Schonlein purpura, Behcet's syndrome, leukocytoclastic vasculitis  
Others:  
o Antiphospholipid syndrome  
o Autoimmune hemolytic anemia  
o Autoimmune glomerulonephritis (including IgA nephropathy, glomerulonephritis rapidly 
progressive, membranous glomerulonephritis, membranoproliferative glomerulonephritis, 
and mesangioproliferative glomerulonephritis)  
o Autoimmune myocarditis/cardiomyopathy  
o Autoimmune thrombocytopenia  
o Goodpasture syndrome  
o Idiopathic pulmonary fibrosis  
o Pernicious anemia  
o Raynaud's phenomenon  
o Sarcoidosis  
o Sjögren's syndrome  
o Stevens-Johnson syndrome  
o Uveitis  
 

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Appendix 11 
Adverse Events: Definitions and Procedures for Recording, 
Evaluating, Follow-up, and Reporting 
Definition of an AE 
AE Definition 
 
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product and which does not necessarily have to have a 
causal relationship with this treatment. 
 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding, for example), symptom, or disease temporally associated with the 
use of a medicinal product, whether or not considered related to the medicinal product. 
 
All AEs fall into one of two categories: “non-serious” or “serious”. 
Events Meeting the AE Definition 
 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or 
other safety assessments (e.g., ECG, radiological scans, vital signs measurements), 
including those that worsen from baseline, considered clinically significant in the 
medical and scientific judgment of the investigator (i.e., not related to a known 
concomitant disease). 
 
Exacerbation of a pre-existing condition including either an increase in frequency 
and/or intensity of the condition. 
 
New conditions detected or diagnosed after trial vaccine administration even though it 
may have been present before the start of the trial. 
 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either trial 
vaccine, including Rabipur® or a concomitant medication/vaccination. 
 
An adverse effect of the trial vaccine, including Rabipur® or concomitant 
medication/vaccination. 
 
An accident or injury. 
Events NOT Meeting the AE Definition  
 
Surgical procedures or other therapeutic interventions themselves are not AEs, but the 
condition for which the surgery/intervention is required is an AE and should be 
documented accordingly. 
 
Planned surgical measures and the condition(s) leading to these measures are not 
AEs, if the condition(s) was (were) known before the period of observation (see below) 
and did not worsen during study. 
In the latter case the condition should be reported as medical history. 
 
Situations in which an untoward medical occurrence did not occur (social and/or 
convenience admission to a hospital). 

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 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the trial that do not worsen. 
Definition of an SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious 
conditions are met. 
An SAE is defined as any untoward medical occurrence that, at any dose: 
 
Results in death. 
 
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. 
 
Requires inpatient hospitalization or prolongation of existing hospitalization: 
In general, hospitalization signifies that the subject has been detained (usually 
involving at least an overnight stay) at the hospital or emergency ward for 
observation and/or treatment that would not have been appropriate in the 
physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfils any other 
serious criteria, the event is serious. When in doubt as to whether “hospitalization” 
occurred or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen 
from baseline is not considered an AE. 
 
Results in persistent disability/incapacity 
The term disability means a substantial disruption of a person’s ability to conduct 
normal life functions. 
This definition is not intended to include experiences of relatively minor medical 
significance such as uncomplicated headache, nausea, vomiting, diarrhea, 
influenza, and accidental trauma (e.g., sprained ankle) which may interfere with or 
prevent everyday life functions but do not constitute a substantial disruption. 
 
Is a congenital anomaly/birth defect in the offspring of the subject. 
 
Is an important medical event: 
Medical or scientific judgment should be exercised in deciding whether SAE 
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 medical or surgical intervention to prevent one 
of the other outcomes listed in the above definition. These events should usually be 
considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment 
in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 

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convulsions that do not result in hospitalization, or development of drug dependency 
or drug abuse. 
Recording of AE and/or SAE 
AE and SAE Recording 
 
When an AE/SAE occurs, it is the responsibility of the investigator to review all 
documentation (e.g., hospital progress notes, laboratory reports, and diagnostics 
reports) related to the event. 
 
The investigator will then record all relevant AE/SAE information in the CRF. 
 
SAEs need to be reported to 
 within 24 hours (see section Reporting of SAEs). 
 
It is not acceptable for the investigator to send photocopies of the subject’s medical 
records to 
 in lieu of completion of the AE/SAE CRF page. 
 
There may be instances when copies of medical records for certain cases are 
requested by 
. In this case, all subject identifiers, with the exception of the subject 
number, will be redacted on the copies of the medical records before submission to 
. 
 
The investigator will attempt to establish a diagnosis of the event based on signs, 
symptoms, and/or other clinical information. Whenever possible, the diagnosis (not the 
individual signs/symptoms) will be documented as the AE/SAE. 
 
AESIs and cases of overdose must be documented and medically assessed by the 
investigator and the outcome described on the SAE/AESI/overdose report form. 
 
Pregnancy must be documented and medically assessed by the investigator and the 
outcome described on the Pregnancy Report Form which is to be sent to 
. 
Assessment of Intensity 
The investigator will make an assessment of intensity for each AE and SAE reported during 
the trial and assign it to 1 of the following categories [25]: 
 
Absent. 
 
Mild: An event that is easily tolerated by the subject, causing minimal discomfort and 
not interfering with everyday activities. 
 
Moderate: An event that causes sufficient discomfort to interfere with normal everyday 
activities. 
 
Severe: An event that prevents normal everyday activities. An AE that is assessed as 
severe should not be confused with a SAE. Severe is a category utilized for rating the 
intensity of an event; and both AEs and SAEs can be assessed as severe. 
An event is defined as ‘serious’ when it meets at least one of the predefined outcomes as 
described in the definition of an SAE, not when it is rated as severe. 
Assessment of Causality 
 
The investigator is obligated to assess the relationship between trial vaccine and each 
occurrence of each AE/SAE. Causality will be determined as: 

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 
Related: There is a reasonable causal relationship between the IMP and the AE. 
 
Unrelated: There is no reasonable causal relationship between the IMP and the 
AE. 
 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, 
and/or arguments to suggest a causal relationship, rather than a relationship cannot be 
ruled out. 
 
The investigator will use clinical judgment to determine the relationship. 
 
Alternative causes, such as underlying disease(s), concomitant therapy or vaccination, 
and other risk factors, as well as the temporal relationship of the event to trial vaccine 
administration will be considered and investigated. 
 
The investigator will also consult the Investigator’s Brochure (IB) and/or Product 
Information for Rabipur® [24], in his assessment. 
 
For each AE/SAE, the investigator must document in the medical notes that he/she 
has reviewed the AE/SAE and has provided an assessment of causality. 
 
There may be situations in which an SAE has occurred and the investigator has 
minimal information to include in the initial report to 
 However, it is very 
important that the investigator always makes an assessment of causality for 
every event before the initial transmission of the SAE data to 
. 
 
The investigator may change his/her opinion of causality in light of follow-up 
information and send a SAE follow-up report with the updated causality assessment. 
 
The causality assessment is one of the criteria used when determining regulatory 
reporting requirements. 
 
All local solicited symptoms are considered related to vaccination. 
Follow-up of AEs and SAEs 
 
The investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by 
 to 
elucidate the nature and/or causality of the AE or SAE as fully as possible. This may 
include additional laboratory tests or investigations, histopathological examinations, or 
consultation with other health care professionals. 
 
If a subject dies during participation in the trial or during the follow-up period, the 
investigator will provide 
with a copy of any post-mortem findings including 
histopathology. 
 
New or updated information will be recorded in the originally completed CRF. 
 
The investigator will submit any updated SAE data to 
 within 24 hours of receipt of 
the information. 

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Reporting of SAEs 
SAE Reporting to 
via Paper CRF 
 
Email or facsimile transmission of the SAE/AESI/overdose paper report form is the 
preferred method to transmit this information to 
/medical monitor or the SAE 
coordinator. 
The investigator will document the date when any employee/co-investigator had first been 
aware of the report and fax or e-mail all SAE reports (initial and follow-up reports) even if 
they are incomplete within 24 hours upon receipt to 
: 
 
In rare circumstances and in the absence of email or facsimile equipment, notification 
by telephone is acceptable with a copy of the SAE data collection tool sent by 
overnight mail or courier service. 
 
Initial notification via telephone does not replace the need for the investigator to 
complete and sign the SAE report form within the designated reporting time frames. 
 
The “initial SAE report” should be as complete as possible, including causality 
assessment, details of the current illness and (S)AE, the reason why the event was 
considered serious; date of onset and end date (if applicable); diagnostic procedures 
and treatment of the event; relevant medical history and concomitant medication and 
vaccinations; and action taken with trial vaccine. The SAE report form must be signed 
by the investigator or his authorized designee(s). 
 
Investigator must inform 
 about AESIs and cases of overdose by applying the 
same timelines and rules of SAEs reporting. 
Determination of Expectedness, Reference Safety Information 
 
Expectedness will be determined by 
 according to the designated Reference 
Safety Information (RSI) provided in the current IB. Any updates or substantial 
amendments will be considered accordingly. 
Observation Period 
 
For the purpose of this trial, the period of observation for collection of AEs extends 
from the time the subject gives informed consent until the end of the trial. 
 
All AEs that occur in the course of the clinical trial regardless of the causal relationship 
should be monitored and followed up until the outcome is known or it is evident that no 
further information can be obtained. 
 
There must be documented reasonable attempts to obtain follow-up information and 
outcome. 
 
It is the responsibility of the investigator to ensure that any necessary additional 
therapeutic measures and follow-up procedures are performed. 

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Post-Trial Events 
 
If the investigator becomes aware of any SAE that occurred after the end of the trial 
but is considered to be caused by the trial vaccine(s), this must be reported to 
. 
 
These SAEs will be processed by 
. Instructions for how to submit these SAEs will 
be provided in a handout in the Investigator Site File. 

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Appendix 12 
Contraceptive Guidance and Collection of Pregnancy 
Information 
Contraceptive Guidance 
Females of childbearing potential must use acceptable methods of birth control from 2 
weeks before the first administration of the test vaccine until 3 months following the 
last administration. The following methods of birth control are acceptable when used 
consistently and correctly:  
 
combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation (oral, intravaginal or transdermal); 
 
progestogen-only hormonal contraception associated with inhibition of ovulation 
(oral, injectable or implantable);  
 
intrauterine devices (IUDs); 
 
intrauterine hormone-releasing systems (IUSs);  
 
bilateral tubal occlusion; 
 
vasectomized partner; 
 
sexual abstinence (periodic abstinence [e.g., calendar, ovulation, symptothermal 
and post-ovulation methods] and withdrawal are not acceptable). 
Males must use reliable forms of contraception (condom) from the moment of the first 
administration of the test vaccine until 3 months following the last administration and 
must refrain from sperm donation from the moment of the first administration of the 
test vaccine until 3 months after the last administration.  
Refer to the Clinical Trial Facilitation Group (CTFG) recommendations on 
contraception and pregnancy testing for further details [23]. 
Reporting and Follow-up of pregnancies 
Pregnancy is an exclusion criterion for enrolment in this trial, but subjects could 
potentially become pregnant during their active participation in this trial. 
Any pregnancy in a subject having received a trial vaccine must be reported to 
 
within 24 hours of the site learning of its occurrence, using a pregnancy reporting 
form. If the subject becomes pregnant during the trial, she will not receive any further 
doses of any sponsor-supplied trial vaccine. The pregnancy must be followed to 
determine outcome, including spontaneous or voluntary termination, details of birth, 
and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. This follow-up should occur even if the 
intended duration of safety follow-up for the trial has ended. 
The trial site should maintain contact with pregnant subjects to obtain pregnancy 
outcome information. 
Any complications during pregnancy (e.g., gestational diabetes or eclampsia) are to 
be considered as an AE; however, these complications could result in the event being 
an SAE. Spontaneous abortions, fetal death, stillbirth and congenital anomalies 
reported in the baby are always considered as SAEs. The pregnancy by itself will not 
be processed as an SAE. The investigator will follow the subject until completion of 
the pregnancy and must assess the outcome in the shortest possible time but not 

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more than 30 days within completion of the pregnancy. The investigator should notify 
 of the outcome of the pregnancy by submitting a Follow-up Pregnancy Report. 

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Appendix 13 
Data Management and Quality Control 
Case report forms 
In this study, all clinical data (including, but not limited to, AE/SAEs, concomitant 
medications/vaccines, medical history, and physical assessments) will be entered 
onto eCRFs in a timely fashion (on the visit day during the staggered enrolment 
phase and within 5 days post-visit for all other visits) by the investigator and/or the 
investigator’s dedicated site staff. All data entered into the eCRF must be verifiable 
against source documents at the trial site. Any changes to the data entered into the 
electronic data capture system will be recorded in the audit trail. 
The investigator will maintain adequate and accurate records for each subject entered 
into the trial. Source documents such as hospital, clinic or office charts, laboratory 
reports, trial worksheets, and signed informed consent documents are to be included 
in the investigator’s files along with subject trial records. 
The sponsor or the CRO will check eCRF entries against source documents 
according to the guidelines of GCP. The consent form will include a statement by 
which subjects allow the sponsor or designee, as well as authorized regulatory 
agencies, to have direct access to source data that support data of the eCRF (e.g., 
subject medical files, appointment books, original laboratory records, etc.). The 
sponsor or designee, bound by secrecy, will not disclose subject identities or personal 
medical information. 
Quality control 
A monitor from the CRO will supervise the trial. The trial monitor will contact the 
investigator regularly to discuss the progress of the trial and to check the trial 
documents including the informed consent forms for completeness and consistency. 
The trial monitor or representative of the sponsor will cross-check the data entered in 
the eCRF with the source data at the trial site in order to verify adherence to the trial 
protocol. 
The eCRF will be checked for completeness and correctness by the monitor and data 
management department of the CRO according to the CRO’s standard operating 
procedures (SOPs). The investigator will resolve any queries. 
Trial site monitoring visits 
Monitoring visits to the trial site will be made periodically during the trial to ensure 
that: 
 The rights and well-being of human subjects are protected 
 The reported study data are accurate, complete and verifiable from the source 
documents and 
 The conduct of the trial is in compliance with the current approved 
protocol/amendment(s), GCP and applicable regulatory requirements.  
The investigator and/or trial staff must make source documents for subjects enrolled 
in this trial available for inspection by CureVac AG or its designee at the time of each 
monitoring visit and sponsor audits, when applicable. These documents must also be 

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available for inspection, verification and copying, as required by regulators, by 
officials of the regulatory health authorities and/or IECs. 
All aspects of the trial and its documentation will be subject to review by the sponsor 
or designee, including but not limited to the Investigator’s Site File, trial vaccine, 
pharmacy records, subject medical records, informed consent documentation, and 
review of eCRFs and associated source documents. It is important that the 
investigator and other trial personnel are available during the monitoring visits and 
that sufficient time is devoted to the process. 
Audits 
The trial site also may be subject to quality assurance audits by the sponsor or 
designees. In this circumstance, the sponsor-designated auditor will contact the site 
in advance to arrange an auditing visit. The auditor may ask to visit the facilities 
where laboratory samples are collected, where the vaccine is stored and prepared, 
and any other facility used during the trial. In addition, there is the possibility that this 
trial may be inspected by regulatory agencies, including those of local (EU-EMA) or 
foreign governments (e.g. US-FDA and others). If the trial site is contacted for an 
inspection by a regulatory body, the sponsor should be notified immediately. The 
investigator and institution guarantee direct access for quality assurance auditors and 
inspectors to all trial documents and source data. 

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Appendix 14 
Protocol Deviations 
The investigator should not deviate from the protocol, except where necessary to 
eliminate an immediate hazard to trial subjects. Should other unexpected 
circumstances arise that will require deviation from protocol-specified procedures, the 
investigator should consult with the Responsible Medical Monitor (and Independent 
Ethics Committee [IEC], as required) to determine the appropriate course of action. 
Protocol deviations due to COVID-19 illness and/or control measures should be 
documented with the reason for the deviation. 

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Appendix 15 
Ethics and Regulations 
Independent ethics committees and competent authorities 
The clinical trial authorization granted by the competent authority (CA) and a 
favorable opinion from the relevant IEC(s) will be obtained prior to the start of the trial. 
The local authorities will be notified about the trial as required by law. 
The CA and the IEC will be notified about the end of the trial and a report 
summarizing the trial results will be sent to the CA and the IEC within 1 year after the 
end of the trial. If the trial is terminated early, the CA and the IEC will be notified 
within 15 days. 
Ethical conduct of the trial 
The trial will be conducted in accordance with the ethical principles set forth in the 
Declaration of Helsinki (including amendments). 
Subject information and consent 
Written informed consent will be obtained from all subjects prior to entry into the trial. 
The investigator will explain to each subject orally and in writing (subject information 
sheet) the nature, significance, risks and implications of the trial before inclusion. In 
particular, the subjects will be informed about the following: 
 The possibility of withdrawing from the clinical trial at any time by 
revoking the consent and without any resulting disadvantage. 
 How personal and health-related data will be collected and used during 
the trial. 
All subjects will receive a copy of the subject information sheet and a copy of their 
signed and dated informed consent form. 
All subjects will be insured against injury caused by their participation in the trial 
according to legal requirements. They will be informed about the insurance and the 
resulting obligations on their part. 
Legal and regulatory requirements 
This trial will be carried out in accordance with GCP as required by European Union 
(EU) Directive 2001/20/EC and the relevant laws and regulations of the country in 
which the trial takes place. 
Insurance policy 
The sponsor will obtain liability insurance covering his and the investigator’s 
responsibility as well as the responsibility of any person involved in the conduct of the 
trial, provided there is proper adherence to the protocol. An insurance certificate will 
be provided by the sponsor to the IEC, if required. 

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Appendix 16 
Biological Samples and Record Retention 
Biological Samples Retention and Destruction 
Collected specimens (blood) will be processed, stored and frozen appropriately for 
analysis. The sponsor has put into place a system to protect subjects’ personal 
information to ensure optimal confidentiality and defined standard processes for 
sample and data collection, storage, analysis, and destruction. Excess biological 
specimens may be further tested with regard to investigation of the vaccine effect. 
Retention of trial records 
Records and source documents pertaining to the conduct of the trial and the 
distribution of the investigational medicinal product (e.g., informed consent forms 
[ICFs], laboratory slips, vaccination inventory records, and other pertinent information) 
must be retained by the investigator for a period of at least 15 years.