An Open, Single Center Phase I Trial to Assess the Safety, Tolerability and Immunogenicity of Two Ascending Doses of the Candidate Vaccine MVA-MERS-S
Phase: PHASE1
Conditions: MERS (Middle East Respiratory Syndrome)
Sponsor: Marylyn Addo

Protocol No. UKE-DZIF1-MVA-MERS-S 
 
 
 
 
 
Confidential 
 
27.11.2018 
Version 6.0 
Page 1 of 55 
    
STUDY PROTOCOL 
 
An open, single center Phase I trial to assess the safety, tolerability and immunogenic-
ity of two ascending doses of the candidate vaccine MVA-MERS-S 
EudraCT No. 
2014-003195-23 
Protocol No. 
UKE-DZIF1-MVA-MERS-S 
Version/Date 
6.0 / 27.11.2018 
Sponsor 
University Medical Center Hamburg-Eppendorf 
Martinistr. 52 
20246 Hamburg, Germany 
 
 
Principal Investigator 
 
 
Prof. Marylyn M. Addo, MD, PhD, MSc, DTM&H 
University Medical Center Hamburg-Eppendorf 
I. Department of Medicine 
Martinistr. 52 
20246 Hamburg, Germany 
 
Telephone:  
+49 (0) 40 7410 51102 
Fax:  
 
+49 (0) 40 7410 58531 
Email:  
m.addo@uke.de 
 
CONFIDENTIALITY STATEMENT 
The information provided in the following document is confidential and is only available for review to 
investigators, potential investigators, the ethics committee and the competent authorities. No disclo-
sure should take place without the written authorization from the sponsor, except to the extent nec-
essary to obtain informed consent from potential subjects or to obtain approval of this protocol by an 
ethics committee or regulatory authorities. 
 

Protocol No. UKE-DZIF1-MVA-MERS-S 
 
 
 
 
 
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Version 6.0 
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Summary of Changes 
 
Summary of changes since last version of approved protocol (protocol version 3.0 to ver-
sion 4.0) 
Amendment Number 
Date of Amend-
ment 
Section Affected  
by Change 
01 
20DEC2017 
2 Synopsis 
Brief description of change: 
The synopsis was updated according to the information given in the main body. 
01 
20DEC2017 
6 Investigator and study administrative structure 
Brief description of change: 
Contact information was updated. 
01 
20DEC2017 
7.4 Risk-benefit considerations 
Brief description of change: 
Additional of information on applied risk management measures. 
Total amount of blood draw corrected. 
01 
20DEC2017 
8.5 Exploratory Objectives 
Brief description of change: 
Clarification that the results from exploratory objectives may not be part of the final study report. 
01 
20DEC2017 
9.3.1 Inclusion Criteria 
Brief description of change: 
No. 4: Addition of tolerated non-clinically significant, minor deviations of laboratory measurements. 
No. 7: Harmonization of information on the duration of using contraception. 
01 
20DEC2017 
9.3.2 Exclusion Criteria 
Brief description of change: 
No. 11: Deletion of migraines. 
01 
20DEC2017 
9.5.2.8.6 Cardiac biomarker 
Brief description of change: 
Correction of tube to be used for blood sampling for analysis of troponin t. 
01 
20DEC2017 
9.5.3.1 Immunogenicity Assays 
Brief description of change: 
Addition of reference to the laboratory manual for detailed information on the blood volume drawn 
for immunogenicity assays. 
01 
20DEC2017 
9.6.5 Archival of documents 
Brief description of change: 
Addition of information on the archival of the TMF. 
01 
20DEC2017 
9.7.1 Definition of Adverse Events, Period of Ob-
servation, Recording of Adverse Events 
Brief description of change: 
Clarification of time window for classification of an AE as solicited. 
01 
20DEC2017 
9.7.2 Severity Categorization of AEs 
Brief description of change: 
Clarification of details on AE grading. 
01 
20DEC2017 
9.8.1.3 Statistical analyses 
Brief description of change: 
Addition of possibility to perform interim analyses. 
 
 

Protocol No. UKE-DZIF1-MVA-MERS-S 
 
 
 
 
 
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Version 6.0 
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Summary of changes since last version of approved protocol (protocol version 4.0 to ver-
sion 5.0) 
Amendment Number 
Date of Amend-
ment 
Section Affected  
by Change 
02 
06FEB2018 
9.3.1 Inclusion Criteria 
Brief description of change: 
No. 4: Concretion of the tolerated non-clinically significant, minor deviations of laboratory measure-
ments. 
 
Summary of changes since last version of approved protocol (protocol version 5.0 to ver-
sion 6.0) 
Amendment Number 
Date of Amend-
ment 
Section Affected  
by Change 
03 
27NOV2018 
Synopsis 
Brief description of change: 
- 
3rd vaccination 12 months after 1st immunization 
03 
27NOV2018 
Study schedule 
Brief description of change: 
Entering study schedule 1b and 2b to reflect the 3rd vaccination and the subsequent follow-up visits  
03 
27NOV2018 
5.3 Subject Information 
Brief description of change: 
Informed consent for study extension 
03 
27NOV2018 
6. Investigators and study administrative structure 
Brief description of change: 
Update of statistician 
03 
27NOV2018 
7.4.1.1 Phlebotomy 
Brief description of change: 
Increase of blood amount  
03 
27NOV2018 
9.3.1 Inclusion Criteria 
Brief description of change: 
No. 11 & 12 applicable contraceptive requirements for 3rd vaccination 
03 
27NOV2018 
9.3.2 Exclusion Criteria 
Brief description of change: 
No. 25: Receipt of any vaccine before and after 3rd vaccination  
03 
27NOV2018 
9.4.1 Treatment Administered 
Brief description of change: 
3rd vaccination was added 
03 
27NOV2018 
9.4.10.3.4 Ambulatory Visits 
Brief description of change: 
Adaption wording 
03 
27NOV2018 
9.4.10.3.5 Ambulatory Vaccination Visit 
Brief description of change: 
Ambulatory vaccination visit for 3rd vaccination 
03 
27NOV2018 
9.4.10.3.6. End-of-study Visit 
Brief description of change: 
End-of-study visit after 3rd vaccination 
03 
27NOV2018 
9.5.2.5 Vital signs 
Brief description of change: 
Deviation for vital signs for 3rd vaccination added 
03 
27NOV2018 
9.5.2.8.2 Hematology 
Brief description of change: 
Analysis of reticulocytes added 

Protocol No. UKE-DZIF1-MVA-MERS-S 
 
 
 
 
 
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03 
27NOV2018 
9.7.1 Definition of Adverse Events, Period of Ob-
servation, Recording of Adverse Events 
Brief description of change: 
List of solicited adverse events complemented/ specified in accordance with events documented in 
the subject diary 
 

Protocol No. UKE-DZIF1-MVA-MERS-S 
 
 
 
 
 
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2 
SYNOPSIS 
Name of Sponsor/Company: 
University Medical Center Ham-
burg-Eppendorf 
Individual Study Table 
Referring to Part 
of the Dossier 
 
 
Volume: 
 
 
Page: 
(For National Authority Use only) 
Name of Finished Product: 
MVA-MERS-S  
Name of Active Ingredient: 
MVA-MERS-S 
Title of Study: 
An open, single center Phase I trial to assess the safety, tolerability 
and immunogenicity of two ascending doses of the candidate vaccine 
MVA-MERS-S 
Principal Investigator 
Prof. Dr. med. M. Addo  
Study center: 
CTC North GmbH & Co. KG 
at the University Medical Center Hamburg-Eppendorf 
Martinistr. 64 
20251 Hamburg, Germany 
Protocol-No. 
UKE-DZIF1-MVA-MERS-S 
EudraCT-No. 
2014-003195-23 
Study Period 
Approx. 7 months per patient (screening to follow-up) 
Total study duration (FPFV to LPLV) approx. 13 months  
 
For subjects who gave consent for a 3rd vaccination (= boost vaccina-
tion one year after 1st vaccination): 
Approx. 10-18 months per patient (screening to follow-up) 
Total study duration (FPFV to LPLV) approx. 18 months total duration 
Phase of development: 
Phase I, first-in-human 
Objectives: 
Primary Objective 
 
To evaluate the safety and tolerability of two dosage levels of the 
experimental vaccine MVA-MERS-S. 
 
To evaluate the reactogenicity after administration of two dosage 
levels of MVA-MERS-S 
Secondary Objectives 
 
To evaluate MERS-S-specific antibody responses induced by two 
dosage levels of MVA-MERS-S 
Exploratory Objectives 
 
To evaluate MERS-S -specific cellular immune responses after ad-
ministration of MVA-MERS-S 
 
To characterize MERS-S -induced B and T cell memory responses 
 
To evaluate innate cell subset phenotypes and function induced by 
MVA-MERS-S  
 
To evaluate early innate immunity gene expression signatures in-
duced by MVA-MERS-S 
 
To comprehensively investigate vaccine-induced humoral immune 
responses and antibody functions 
Study Design 
Single-center, open-label, ascending dose phase I study 

Protocol No. UKE-DZIF1-MVA-MERS-S 
 
 
 
 
 
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Methodology: 
This will be a Phase I, single-center trial in 24 healthy adults aged 18 to 
55 years. 
    
Subjects will be allocated in two cohorts of 12 subjects each receiving 
two single vaccine injections 28 days apart. Vaccination of subjects in 
each cohort will proceed in a staggered manner. 
 
Cohort 
No. of vaccine 
injections 
Dose per in-
jection 
No. of        
subjects 
1 
2 
107 pfu 
12 
2 
2 
108 pfu 
12 
 
For subjects who gave consent for a 3rd vaccination (= boost vaccina-
tion one year after 1st vaccination): 
Eligible subjects will receive a 3rd vaccination as a booster 12 months 
(±4 months) after the 1st vaccination. 
Cohort 
No. of vaccine 
injections 
Dose per in-
jection 
No. of        
subjects 
1 
3 
107 pfu 
boost at 12 
months: 
108 pfu 
max. 12 
2 
3 
108 pfu 
max. 12 
 
Safety considerations for dosing and dose-escalation: 
The study is designed to establish safety, tolerability and immunogenic-
ity of MVA-MERS-S, a MERS Vaccine candidate, investigated at two 
different dose levels in 24 healthy adults in Germany.  
An interim safety report, summarizing the safety (AEs, vital signs, 12-
lead ECGs, and laboratory safety data) will be prepared and reviewed 
by the Principal Investigator and Medical Monitor before the second im-
munization for each dose cohort.  
Planned dose escalation will occur after the second immunization of all 
subjects of the 1st dose group following a review of the interim safety 
report summarizing the safety (AEs, vital signs, 12-lead ECGs, and la-
boratory safety data) and any available immunological data by the Prin-
cipal Investigator and Medical Monitor. 
Number of subjects: 
24 (12 per cohort) 
Diagnosis and main criteria for 
inclusion: 
Key inclusion criteria: 
 
Written informed consent form 
 
Healthy male and female subjects aged 18-55 years.  
 
No clinically significant health problems as determined during med-
ical history and physical examination at screening visit. 

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 
Body mass index 18.5 - 30.0 kg/m2 and weight > 50 kg at screening. 
 
Non-pregnant, non-lactating female with negative pregnancy test. 
 
Males and females who agree to comply with the applicable contra-
ceptive requirements of the protocol as defined above from day 0 to 
day 56 (males) and 7 days prior vaccination to day 56 (females), re-
spectively.   
Additional criteria for the subjects receiving the 3rd vaccination: 
 
Males and females who agree to comply with the applicable contra-
ceptive requirements of the protocol as defined above from day 0 to 
day 28 of the 3rd vaccination (males) and 7 days prior to 3rd vaccina-
tion to day 28 after the 3rd vaccination (females), respectively.   
 
Key exclusion criteria: 
 
Receipt of any vaccine in the 2 weeks prior to 1st trial vaccination 
(4 weeks for live vaccines) or planned receipt of any vaccine in the 
3 weeks following the 2nd trial vaccination.  
 
Previous MVA immunization. 
 
Known allergy to the components of the MVA-MERS-S vaccine 
product. 
 
Known history of anaphylaxis to vaccination or any allergy likely to 
be exacerbated by any component of the trial vaccine. 
 
Evidence in the subject's medical history or in the medical examina-
tion that might influence either the safety of the subject or the ab-
sorption, distribution, metabolism or excretion of the investigational 
product. 
 
Clinically relevant findings in ECG, in particular prolonged QTc (B) 
of > 450 msec in males and > 460 msec in females. 
 
Evidence in the subject's medical history or in the medical exami-
nation that might influence either the safety of the subject or the 
absorption, distribution, metabolism or excretion of the investiga-
tional product under investigation. 
 
 Any confirmed or suspected immunosuppressive or immunodefi-
cient condition, cytotoxic therapy in the previous 5 years, and/or di-
abetes. 
 
Any chronic or active neurologic disorder, including seizures, and 
epilepsy, excluding a single febrile seizure as a child. 
 
Additional criteria for the subjects receiving the 3rd vaccination: 
 
Receipt of any vaccine in the 2 weeks prior to (4 weeks for live vac-
cines) or 3 weeks following to 3rd trial vaccination. 
Test product, dose and mode 
of administration, batch num-
ber: 
Test product: MVA-MERS-S 
Dose: 
 
In Cohort 1, 12 fasted subjects will receive 2 single doses of 
1 x 107 pfu50 MVA-MERS-S in 0.5mL (total injected volume 1mL). 
 
In Cohort 2, 12 fasted subjects will receive 2 single doses of 
1 x 108 pfu50 MVA-MERS-S in 0.5mL (total injected volume 1mL). 
 
In addition, irrespective of cohort, eligible subjects that consent to 
participate in and are eligible for a 3rd boost vaccination will receive 

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a 3rd single dose of 1 x 108 pfu MVA-MERS-S in 0.5mL (the total in-
jected volume will then be 1.5mL). 
 
The relative concentration of the test product is 2x107 pfu50 /ml and 
2x108 pfu50 /ml, respectively. 
Dose administration on day 0 and day 28 for each subject. Dose esca-
lation will occur following a review of the interim safety report.  
 
For eligible subjects, the 3rd vaccination will be administered 12 months 
after 1st vaccination ± 4 months.  
 
Mode of administration: 
Intramuscular (i.m.) 
Duration of Treatment: 
Subjects will receive two single vaccine injections, one on day 0 and an-
other on day 28. 
In addition, eligible subjects will receive a boost vaccination 12 months 
(± 4 months) after the 1st vaccination. 
Reference therapy, dose and 
mode of administration, batch 
number: 
None 
Criteria for evaluation: 
 
Primary Endpoints:  
The nature frequency and severity of adverse events associated with 
MVA-MERS-S vaccine will be collected and measured as followed: 
 
 
Occurrence of solicited local reactogenicity signs and symptoms 
for 14 days after vaccination. 
 
Occurrence of solicited systemic reactogenicity signs and symp-
toms for 14 days after vaccination 
 
Occurrence of unsolicited adverse events (AE) for 28 days after 
vaccination 
 
Change from baseline of safety laboratory measures  
 
Occurrence of serious adverse events (SAE) throughout the 
study period 
 
Secondary Endpoints: 
Immunogenicity 
 
Humoral immunity: Magnitude of MVA-MERS-S antibody re-
sponses 
Safety: 
Safety data (AEs, SAEs and Vital Signs) will be collected at all study 
visits. 
 
Laboratory safety test (biochemistry, hematology and dipstick urinalysis) 
will be performed at screening, pre-dose and at study follow-up visit. 
Statistical methods: 
Metric data will be summarized using descriptive statistics (number, 
mean, standard deviation, minimum, median and maximum). Categori-
cal data will be summarized by using frequency tables (frequency and 
percent). It is not planned to test any hypotheses in a confirmatory 
sense. 
 

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STUDY SCHEDULES 
Table 1a 
Phase of study 
SCR 
Confinement 
 
Ambulatory 
Visits 
Confinement 
Ambulatory Visits 
End 
of 
study 
Study day 
-28- 
-2 
-1 
0 
1 
3 
7 
14 
(±2) 
27 
28 
29 
35 
42 
(±2) 
56 
(±3) 
84 
(±3) 
180 
(±7) 
Informed Consent 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
I/E Criteria 
√ 
√ 
 
 
 
 
 
√ 
 
 
 
 
 
 
 
Medical History/ De-
mographics 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Update Medical History 
 
√ 
 
 
 
 
 
√ 
 
 
 
 
 
 
 
Physical Examination 
√ 
√a 
 
 
 
 
 
√a 
 
 
 
√a 
 
 
√ 
Height and Weight 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
√c 
Vital Signs 
√ 
√ 
√ d 
√ 
√ 
√ 
√ 
√ 
√ 
d 
√ 
√ 
√ 
√ 
√ 
√ 
12-lead ECG 
√ 
 
 
 
 
√ 
√ 
 
√ 
 
√ 
√ 
 
 
 
Ambulatory Visit 
√ 
 
 
 
√ 
√ 
√ 
 
 
 
√ 
√ 
√ 
√ 
√ 
Confinement 
 
√ 
√ 
√e 
 
 
 
√ 
√ 
√e 
 
 
 
 
 
Dosing  
 
 
√i 
 
 
 
 
 
√i 
 
 
 
 
 
 
Injection site & sys-
temic events/ reactions 
assessment 
 
 
√ d 
√ 
√ 
√ 
√ 
 
√ 
d 
√ 
√ 
√ 
 
 
√ 
Temperature 
√ 
 
√ d 
√ 
√ 
√ 
√ 
 
√ 
d 
√ 
√ 
√ 
√ 
√ 
√ 
Alcohol Breath Test 
√ 
√ 
 
 
 
 
 
√ 
 
 
 
 
 
 
 
Discharge 
 
 
 
√ 
 
 
 
 
 
√ 
 
 
 
 
 
Training/ Dispensing 
subject diary 
 
 
√ 
 
 
 
 
 
√ 
 
 
 
 
 
 
Review/ Collection of 
subject diary 
 
 
 
√ 
√ 
√ 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
Adverse Events & 
Concomitant medica-
tion 
 
 
√d 
√ 
√ 
√ 
√ 
√ 
√d 
√ 
√ 
√ 
√ 
√ 
√ 
Laboratory Analysis 
Phase of study 
SCR 
Confinement 
Ambulatory 
Visits 
Confinement 
Ambulatory Visits 
End 
of 
Study 
Study day 
-28- 
-2 
-1 
0 
1 
3 
7 
14 
(±2) 
27 
28 
29 
35 
42 
(±2) 
56 
(±3) 
84 
(±3) 
180 
(±7) 
Troponin T 
√ 
 
 
 
 
√ 
√ 
 
√ 
 
√ 
√ 
 
 
√ 
Safety Lab blood (Clin-
ical Chemistry, Hema-
tology) 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
 
√ 
√ 
√ 
 
 
√ 
Safety Lab Urine 
√ 
√ 
 
 
 
√ 
√ 
√ 
 
 
√ 
√ 
 
 
√ 
HIV/HBV/HCV Serol-
ogy 
√ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine Drug Screen 
√ 
√ 
 
 
 
 
 
√ 
 
 
 
 
 
 
 
Pregnancy Test 
√ h 
√ 
g 
 
 
 
 
 
√ g 
 
 
 
 
 
 
√h 
Anti-MVA-MERS Elisa 
 
 
√ 
 
 
√ 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
Neutralization Assay 
 
 
√ 
 
 
√ 
√ 
 
√ 
 
√ 
√ 
√ 
√ 
√ 
T-cell response 
 
 
√ 
 
 
√ 
√ 
 
√f 
 
√ 
√ 
√ 
√ 
√ 
RNA blood sample 
storage 
 
 
√ 
√ 
√ 
√ 
 
 
√ f 
√ 
√ 
 
 
 
 

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Innate immunity 
 
 
√ 
√ 
√ 
√ 
 
 
√ 
√ 
√ 
 
 
 
 
PBMC freezing and 
plasma aliquots 
 
 
√ 
√ 
√ 
√ 
√ 
 
√ 
f 
√ 
√ 
√ 
√ 
√ 
√ 
 
 
 
 
Table 2b 
3rd boost vaccination 8-16 months after initial vaccination  
 
Phase of study 
Phone 
Call 
Dosing 
Ambulatory 
Visits 
End of 
study 
Study day 
≥ - 7  
0 
1 
3 
7 
14 (±2) 
28(±2) 
Informed Consent 
 
√f 
 
 
 
 
 
I/E Criteria 
 
√f 
 
 
 
 
 
Update Medical History 
 
√f 
 
 
 
 
 
Physical Examination 
 
√af 
 
 
 
 
 
 Weight 
 
√fc 
 
 
 
 
 
Vital Signs 
 
√ d 
√ 
√ 
√ 
√ 
√  
12-lead ECG 
 
√f 
 
 
 
 
 
Ambulatory Visit 
 
√ 
√ 
√ 
√ 
√ 
√ 
Dosing  
 
√i 
 
 
 
 
 
Injection site & systemic 
events/ reactions as-
sessment 
 
√ d 
√ 
√ 
√ 
√ 
√ 
Temperature 
 
√ d 
√ 
√ 
√ 
√ 
√  
Alcohol Breath Test 
 
√f 
 
 
 
 
 
Training/ Dispensing 
subject diary 
 
√ 
 
 
 
 
 
Review/ Collection of 
subject diary 
 
 
√ 
√ 
√ 
√ 
√ 
Adverse Events & Con-
comitant medication 
 
√d 
√ 
√ 
√ 
√ 
√ 
Phone call 
√ 
 
 
 
 
 
 
Laboratory Analysis 
Phase of study 
Phone 
Call 
Dosing 
Ambulatory Visits 
End of 
Study 
Study day 
 
0 
1 
3 
7 
14 (±2) 
28(±2) 
Troponin T 
 
√ 
 
 
 
 
√ 
Safety Lab blood (Clini-
cal Chemistry, Hematol-
ogy) 
 
√ 
√ 
√ 
√ 
√ 
√ 
Safety Lab Urine 
 
√ 
 
 
√ 
√ 
√ 
Urine Drug Screen 
 
√ 
 
 
 
 
 
Pregnancy Test 
 
√ fh 
 
 
 
 
√h 
Anti-MVA-MERS Elisa 
 
√ 
 
 
√ 
√ 
√ 
Neutralization Assay 
 
√ 
 
 
√ 
√ 
√ 
T-cell response 
 
√ 
 
 
√ 
√ 
√ 
RNA blood sample stor-
age 
 
√ 
√ 
√ 
√ 
 
 

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Innate immunity 
 
√ 
√ 
√ 
√ 
 
 
PBMC freezing and 
plasma aliquots 
 
√ 
√ 
√ 
√ 
√ 
√  
a  Symptom-targeted physical examination 
b  Please refer to Table  for frequency of vital signs examinations 
c Only weight 
d Please refer to Table  for frequency of Adverse Events and Concomitant Medication questioning. 
e Morning check-out 
f Before immunization 
g Serum pregnancy test 
h Urine pregnancy test 
I Subjects will be monitored and evaluated for AEs for at least 30 minutes after vaccination in attendance of an investigator 
 
 
Table 2a: Detailed Time and Events 
Study 
Day 
Time after Dose 
administration 
(hours) 
 
Dosing 
Vital 
Signs 
Temperature 
Adverse 
Events/ 
Con Med 
Injection site/ 
systemic reac-
tion/ Events as-
sessment 
0 
01 
√ 
√ 
√ 
√ 
 
0 
2 
 
√ 
√ 
√ 
√ 
0 
4 
 
√ 
√ 
√ 
√ 
0 
6 
 
√ 
√ 
√ 
√ 
0 
8 
 
√ 
√ 
√ 
√ 
0 
12 
 
√ 
√ 
√ 
√ 
1 
24 
 
√ 
√ 
√ 
√ 
28 
01 
√ 
√ 
√ 
√ 
√ 
28 
2 
 
√ 
√ 
√ 
√ 
28 
4 
 
√ 
√ 
√ 
√ 
28 
6 
 
√ 
√ 
√ 
√ 
28 
8 
 
√ 
√ 
√ 
√ 
28 
12 
 
√ 
√ 
√ 
√ 
29 
24 
 
√ 
√ 
√ 
√ 
 1 Events must be completed before dose administration 
 
Table 2b: Detailed Time and Events for 3rd vaccination 
 
Study 
Day 
Time after Dose 
administration 
(hours) 
 
Dosing 
Vital 
Signs 
Temperature 
Adverse 
Events/ 
Con Med 
Injection site/ 
systemic reac-
tion/ Events as-
sessment 
0 
01 
√ 
√ 
√ 
√ 
 
0 
2 
 
√ 
√ 
√ 
√ 
0 
4 
 
√ 
√ 
√ 
√ 
0 
6 
 
√ 
√ 
√ 
√ 
 

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3 
TABLE OF CONTENTS 
 
STUDY PROTOCOL ................................................................................................................................ 1 
1 
SIGNATURES .................................................................................................................................. 2 
2 
SYNOPSIS ....................................................................................................................................... 6 
3 
TABLE OF CONTENTS ................................................................................................................. 13 
4 
LIST OF ABBREVIATIONS ............................................................................................................ 15 
5 
ETHICS .......................................................................................................................................... 17 
5.1 
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) ........................... 17 
5.2 
Ethical Conduct of the Study ................................................................................................. 17 
5.3 
Subject Information and Consent.......................................................................................... 17 
5.4 
Confidentiality ........................................................................................................................ 17 
5.5 
Insurance .............................................................................................................................. 17 
5.6 
Publication Policy .................................................................................................................. 18 
5.7 
Qualification of the Investigator............................................................................................. 18 
6 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE .............................................. 19 
7 
INTRODUCTION ............................................................................................................................ 21 
7.1 
Background and Rationale .................................................................................................... 21 
7.2 
MERS Vaccine Development and Preclinical Studies Using the MVA-MERS-S Vaccine 
Vector ................................................................................................................................... 21 
7.3 
Clinical Experience available for MVA-MERS-S ................................................................... 22 
7.4 
Risk-benefit considerations ................................................................................................... 22 
7.4.1 
Potential Risks for Study Participants ........................................................................... 22 
8 
STUDY OBJECTIVES .................................................................................................................... 24 
8.1 
Primary Objective .................................................................................................................. 24 
8.2 
Primary Endpoints ................................................................................................................. 24 
8.3 
Secondary Objective ............................................................................................................. 24 
8.4 
Secondary Endpoints ............................................................................................................ 24 
8.5 
Exploratory Objectives .......................................................................................................... 24 
9 
INVESTIGATIONAL PLAN ............................................................................................................. 24 
9.1 
Overall Study Design and Plan: Description ......................................................................... 24 
9.2 
Discussion of Study Design, Including the Choice of Control Groups .................................. 24 
9.3 
Selection of Study Population ............................................................................................... 25 
9.3.1 
Inclusion Criteria ............................................................................................................ 25 
9.3.2 
Exclusion Criteria ........................................................................................................... 25 
9.3.3 
Removal of Subjects from Therapy or Assessment ...................................................... 27 
9.4 
Treatments ............................................................................................................................ 29 
9.4.1 
Treatments Administered .............................................................................................. 29 
9.4.2 
Identity of Investigational Medicinal Product ................................................................. 30 
9.4.3 
Preparation and Administration ..................................................................................... 31 
9.4.4 
Method of Assigning Subjects to Treatment Groups ..................................................... 32 
9.4.5 
Selection of Doses in the Study .................................................................................... 32 
9.4.6 
Selection and Timing of Dose for Each Subject ............................................................ 32 
9.4.7 
Blinding .......................................................................................................................... 32 
9.4.8 
Prior and Concomitant Therapy .................................................................................... 32 
9.4.9 
Rescue Medication ........................................................................................................ 32 

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9.4.10 
Treatment Compliance .................................................................................................. 32 
9.5 
Study Procedures and Examinations .................................................................................... 37 
9.5.1 
Screening Procedures ................................................................................................... 37 
9.5.2 
Study Examinations ....................................................................................................... 37 
9.5.3 
Pharmacodynamic Measurements ................................................................................ 41 
9.5.4 
Pharmacogenetic Measurements .................................................................................. 44 
9.6 
Data Quality Assurance ........................................................................................................ 44 
9.6.1 
Quality Assurance System ............................................................................................ 44 
9.6.2 
Monitoring ...................................................................................................................... 44 
9.6.3 
Documentation and Data Collection .............................................................................. 44 
9.6.4 
Data Management ......................................................................................................... 44 
9.6.5 
Archival of documents ................................................................................................... 45 
9.7 
Adverse Events ..................................................................................................................... 45 
9.7.1 
Definition of Adverse Events, Period of Observation, Recording of Adverse Events ... 45 
9.7.2 
Severity Categorization of AEs ...................................................................................... 46 
9.7.3 
Relationship Categorization .......................................................................................... 46 
9.7.4 
Outcome Categorization ................................................................................................ 46 
9.7.5 
Clinical Laboratory Evaluations ..................................................................................... 47 
9.7.6 
Abuse, Misuse, Overdose, and Medication Error .......................................................... 47 
9.7.7 
Serious Adverse Event (SAE) Procedures .................................................................... 47 
9.7.8 
Definition of serious adverse reaction (SAR) ................................................................ 48 
9.7.9 
Definition of suspected unexpected serious adverse reaction (SUSAR) ...................... 48 
9.7.10 
Regulatory Agency, Independent Ethics Committee, and Investigative Site Reporting 48 
9.7.11 
Assessment of Severity ................................................................................................. 48 
9.8 
Statistical Methods Planned in the Protocol and Determination of Sample Size ................. 51 
9.8.1 
Statistical and Analytical Plan ....................................................................................... 51 
9.8.2 
Determination of Sample Size ....................................................................................... 51 
9.9 
Changes in the conduct of the study or planned analysis .................................................... 51 
9.10 
Local Safety Board ................................................................................................................ 52 
10 
REPORTS ...................................................................................................................................... 52 
10.1 
Final Report ........................................................................................................................... 52 
10.2 
Additional reports .................................................................................................................. 53 
11 
REFERENCES ............................................................................................................................... 54 
 
 

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4 
LIST OF ABBREVIATIONS 
ADR 
Adverse Drug Reaction 
AE 
Adverse Event 
ALP 
Alkaline phosphatase 
ALT 
Alanine transaminase 
AMG 
Gesetz über den Verkehr mit Arzneimitteln (Arzneimittelgesetz) 
AST 
Aspartate transaminase 
cm 
Centimeter 
CoV 
Coronavirus 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C reactive protein 
CV 
Coefficient of Variation 
DMP 
Data Management Plan 
DRM 
Data Review Meeting 
DZIF 
German Center of Infectious Diseases Research (Deutsches Zentrum 
für Infektionsforschung) 
ECG 
Electrocardiogram 
EDTA 
Ethylene Diamine Tetra-acetic Acid 
ELISA 
Enzyme-linked Immunosorbent Assay 
EliSpot 
Enzyme-linked Immunosorbent Spot 
EU 
European Union 
FDA 
Food and Drug Administration 
FIH 
First in human 
FIM 
First in Man 
FOCP 
Female of Child-bearing Potential 
GCP 
Good Clinical Practice 
GCP-V 
Regulations on the implementation of Good Clinical Practice in the con-
duct of clinical trials on medicinal products for human use (GCP Ver-
ordnung) 
GeoM 
Geometric Mean 
GGT 
Gamma glutamyl transferase 
GLP 
Good Laboratory Practice 
H 
Hour 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
i.m. 
Intramuscular 
IB 
Investigator’s Brochure 
ICH 
International Conference on Harmonization of Technical Requirements 
for Registration of Pharmaceuticals for Human Use 
ICS 
Intracellular Cytokine Staining 
ID 
Identification 
IEC 
Independent Ethics Committee 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 

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kg 
Kilogram 
KSA 
Kingdom of Saudi Arabia 
LDH 
Lactate dehydrogenase 
MAH 
Marketing Authorization Holder 
Max 
Maximum 
MCH 
Mean corpuscular hemoglobin 
MCHC 
Mean corpuscular hemoglobin concentration 
MCV 
Mean corpuscular volume 
MDRD 
Modification of Diet in Renal Disease 
Mean 
Arithmetic mean 
Med 
Median 
MedDRA 
Medical Dictionary for Regulatory Activities 
MERS 
Middle East Respiratory Syndrome 
MET 
Methamphetamine 
mg 
Milligram 
Min 
Minimum 
mL 
Milliliter 
mmHg 
Millimeters of mercury 
msec 
Millisecond 
MTDMVA 
Modified Vaccine Ankara 
MVA 
Modified Vaccinia Virus Ankara 
N 
Number 
NHP 
Non-Human Primates 
PBMC 
Peripheral Blood Mononuclear Cell 
PEI 
Paul Ehrlich Institute 
PFU 
Plaque-forming Unit 
PI 
Principal Investigator 
QAU 
Quality Assurance Unit 
RBC 
Red blood cells 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAR 
Serious Adverse Reaction 
SARS 
Severe Acute Respiratory Syndrome 
SD 
Standard Deviation 
SDV 
Source Data Verification 
SmPC 
Summary of Product Characteristics 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected unexpected Serious Adverse Reaction 
TCA 
Tricyclic Antidepressants 
THC 
Tetrahydrocannabinol 
TMF 
Trial Master File 
WBC 
White blood cell 
WHO 
World Health Organization 

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5 
ETHICS  
5.1 
Independent Ethics Committee (IEC) or Institutional Review Board (IRB) 
This study will be planned and performed in accordance with  
 The Declaration of Helsinki in its version of Fortaleza, 2013; 
 The EU Clinical Trial Directive 2001/20/EC; 
 The "Note for Guidance on Good Clinical Practice" (CPMP/ICH/135/95 of January 17, 1997); 
 The German Drug Law (Arzneimittelgesetz), in the current version; 
 GCP-Verordnung from August 9, 2004 (GCP-Regulation) 
and other applicable laws. 
5.2 
Ethical Conduct of the Study  
The sponsor authorizes CTC North to make all necessary applications. 
CTC North will submit, among other documents, the study protocol, the subject information and the 
informed consent form to the 'Ethik-Kommission der Ärztekammer Hamburg' and request approval (fa-
vorable opinion). CTC North will provide the clinical trial application to the competent authority (PEI). 
CTC North will notify the beginning (first subject’s screening) and the end (last subject’s last visit) of this 
trial and all amendments to the local Hamburg authority in accordance with § 67 Abs. 1 AMG.  
The approval of both, the ethics committee and the PEI must be obtained prior to the start of the study. 
Copies of the original approval documents will immediately be sent to the sponsor and will be included 
in the study report. A list of the members of the IEC will also be provided with the final report. 
5.3 
Subject Information and Consent 
An investigator will explain to the subjects the nature, significance and implications of the study prior to 
the clinical examination. The investigator will explain all methods, rules of conduct and any restrictions 
which may apply. Possible effects and side effects will be discussed. Subjects will be informed that they 
are free to withdraw from the study at any time, without giving any reason for doing so. They must be 
able to understand the full implications of their decision.  
All participants will sign an informed consent form as evidence of consent. The subject information sheet 
and the informed consent form of each participant will be filed in the ISF. A second original of the signed 
consent form and a copy of the information sheet will be handed to the subjects after signature and 
before enrollment. 
All participants will be informed about the extension of the study and the 3rd vaccination. Subjects willing 
to participate in a 3rd vaccination as a one-year boost after the initial vaccination, will be informed about 
the nature, significance and implications of the additional boost as part of this study by an investigator 
in a separate meeting prior to the clinical examination. The investigator will explain all methods, rules of 
conduct and any restrictions which may apply. Possible effects and side effects of the 3rd vaccination 
will be discussed and all subjects will sign the current version of the informed consent form as evidence 
of their consent.  
5.4 
Confidentiality 
The investigator must assure that subjects’ anonymity will be strictly maintained and that their identities 
are protected from unauthorized parties. Only an identification code (i.e., consists of identification num-
ber, sex and year of birth) should be recorded on any form or biological sample submitted to the labor-
atory, sponsor or IEC. The investigator must keep a screening log showing codes and names for all 
subjects screened and for all subjects enrolled in the trial. 
5.5 
Insurance 
The sponsor is responsible for the appropriate insurance coverage for the subjects. Sponsor will take 
out insurance coverage for the subjects before regulatory submission, and the insurance certificate will 
be filed in the trial master file (TMF). 

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5.6 
Publication Policy 
The sponsor has to publish the result of this study in accordance with § 42b AMG. Beside it is in the 
sole discretion of the sponsor whether or not to publish the results of this study. The trial will be regis-
tered at clinicaltrials.gov.  
5.7 
Qualification of the Investigator 
The Principal Investigator (PI) and his deputies fulfill the requirements of German law 
(§ 40 Abs. 1, Nr. 5 AMG). Curriculum vitae of the PI and deputies will be filed in the TMF. 
For conducting the study the PI may delegate tasks to physicians (sub-investigators) or other qualified 
staff. This is to be documented properly. The PI is responsible for the adequate training and supervision 
of all delegates. No study related procedure must be performed by personnel which is not properly 
trained and delegated. 
In the present document the mere term “Investigator” refers to the Principal Investigator or a sub-inves-
tigator. 
 
 

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6 
INVESTIGATORS AND STUDY ADMINISTRATIVE STRUCTURE 
 
 
Sponsor: 
University Medical Center Hamburg-Eppendorf 
 
 Martinistr. 52, 20246 Hamburg, Germany 
 
Principal Investigator: 
Prof. Marylyn M. Addo 
 
 I. Med. Department 
 
University Medical Center Hamburg-Eppendorf 
 
 Martinistr. 52, 20246 Hamburg, Germany 
 
 Phone:  
+49 40 7410 51102 
 
 Fax: 
 
+49 40 7410 58531 
 
 Email:   
m.addo@uke.de  
 
Deputy: 
 Dr. med. Alen Jambrecina 
 
CTC North GmbH & Co. KG 
 
 Martinistr. 64, 20251 Hamburg, Germany 
 
 Phone:  
+49 40 524719 400 
 
 Fax: 
 
+49 40 524719 148 
 
 Email:   
a.jambrecina@ctc-north.com  
 
Deputy: 
Dr. med. Stefan Schmiedel 
 
 I. Med. Department 
 
University Medical Center Hamburg-Eppendorf 
 
 Martinistr. 52, 20246 Hamburg, Germany 
 
 Phone:  
+49 40 7410 52346 
 
 Fax: 
 
+49 40 7410 56832 
 
 Email:   
s.schmiedel@bni-hamburg.de  
 
Medical Monitor: 
Prof. Dr. med. Jan Rupp 
 
Infectious Diseases 
 
DZIF Clinical Trials Unit 
 
 University of Lübeck 
 
Clinical CRO 
CTC North GmbH & Co. KG 
 
 at the University Medical Center Hamburg-Eppendorf  
 
 Martinistr. 64, 20251 Hamburg, Germany 
 
 
Clinical Trial Management: 
Dr. Saskia Borregaard 
 
 CTC North GmbH & Co. KG 
 
 Phone:  
+49 40 524719 200 
 
 Fax:  
 
+49 40 524719 119 
 
 Email:   
s.borregaard@ctc-north.com  
 
Project Manager: 
 Laura Kaltenberg 
 
 CTC North GmbH & Co. KG 
 
 Phone:  
+49 40 524719 214 
 
 Fax:  
 
+49 40 524719 129 
 
 Email:   
l.kaltenberg@ctc-north.com  
 
 
 
 

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Clinical Monitor: 
Ullrich Twisselmann 
 
 CTC North GmbH & Co. KG 
 
Data Manager: 
Noelia Carabelos 
 
 CTC North GmbH & Co. KG 
 
 Phone:  
+49 40 524719 242 
 
 Fax: 
 
+49 40 524719 129 
 
 Email:   
n.carabelos@ctc-north.com  
 
Statistician: 
Angelika Böhm 
 
 Staburo GmbH 
 
Aschauer Str. 30a, 81549 München, Germany 
 
 Phone:  
+49 89 55271520 
 
Fax: 
 
+49 89 55271519 
 
Email:  
kraemer@staburo.de 
 
Safety Laboratory  
Center for Diagnostics 
 
 University Medical Center Hamburg-Eppendorf 
 
 Martinistr. 52, 20246 Hamburg 
 
 Germany 
 
 Phone:  
+49 40 7410 59271 
 
 Fax: 
 
+49 40 7410 57576 
 
 
Immunogenicity Laboratories: 
 
 
Humoral Immunity / Antibody responses 
Cellular and Innate Immunity 
Prof. Stephan Becker 
Institute for Virology 
Philipps University Marburg 
Hans Meerweinstr. 2 
35043 Marburg, Germany 
Phone: +49 6421 286253 
Fax: 
+49 6421 2868962 
Email becker@staff.uni-marburg.de 
Prof. Marylyn M. Addo  
PD Julian Schulze-zur-Wiesch 
 
ZIM, 1. Medizinische Klinik, UKE 
c/o Heinrich-Pette-Institut 
Leibnitz-Institut für Experimentelle Virologie 
Martinistr. 52, 20251 Hamburg,  Germany 
Phone:  
+49 40 7410 51102 
Fax:  
 
+49 40 7410 58531 
Mobile:  
+49 152 2282 7525 
Email:   
m.addo@uke.de  
Humoral Immunity / Antibody responses 
TCR and Cellular Immunity 
Prof. Florian Klein 
Labor für Experimentelle Immunologie 
Klinik I für Innere Medizin 
Zentrum für Molekulare Medizin 
Universität zu Köln 
Robert-Koch-Str. 21, Gebäude 66,  
50931 Köln, Germany 
Phone: +49 221 478 89693  
Email florian.klein@uk-koeln.de  
Dr. Cesar Munoz-Fontela  
 
 
Bernhard-Nocht-Institut für Tropenmedizin 
Bernhard-Nocht-Straße 74 
20359 Hamburg, Germany 
Phone:  
+49 40 42818-0 
Email:   
cesar.munoz-fontela@hpi.uni-
hamburg.de  
 

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7 
INTRODUCTION 
7.1 
Background and Rationale 
MERS and the need for a MERS Vaccine 
In the aftermath of the dramatic and unprecedented Ebola outbreak in West-Africa 2013-2016, for which 
the world and scientific community were ill-prepared, the WHO has initiated a Research and Develop-
ment “Blueprint Initiative for action to prevent epidemics” (http://www.who.int/csr/research-and-develop-
ment/blueprint/en/). In this context WHO convened an ad-hoc expert group to synthesize lessons 
learned from past global health experiences and agreed on a list of emerging pathogens likely to cause 
severe outbreaks and for which no or limited medical countermeasures exist (http://www.who.int/medi-
cines/ebola-treatment/WHO-list-of-top-emerging-diseases/en/). MERS-CoV, the causative agent of the 
Middle Eastern Respiratory syndrome (MERS) is one of the eight priority organisms for which such 
preparedness efforts will be initiated through international collaboration and the current vaccine trial falls 
under this umbrella funded by the German Center of Infectious Diseases Research (DZIF).  
 
MERS is a potentially fatal disease under tight epidemiologic control by the WHO and currently without 
registered prevention or treatment option. The first case of MERS-CoV infection was identified in a pa-
tient with acute pneumonia and renal failure in the Kingdom of Saudi Arabia (KSA) in June 2012 [1]. As 
of December 6, 2016 1842 laboratory-confirmed cases of MERS-CoV, more than 652 deaths and 27 af-
fected countries have been registered by WHO, mainly in the middle east, but also South Korea, the 
United Kingdom, France and Germany [2]. Three cases have been imported to Germany, all of which 
fatal and recently in September 2016 the second case has been imported to Austria. Transmission of 
the virus is from man-to-man and from human contact with non-human sources of virus, potentially 
dromedary camels. The current hypothesis is that primary cases result from transmission from camels-
to-humans and secondary transmission takes place from human-to-human in the nosocomial setting. 
The virus affects men and women at all ages with severe courses of disease. Up to 40 % lethality has 
been reported for patients with comorbidities. Disease severities induced by MERS-CoV infections vary 
from silent infections over mild respiratory symptoms to severe pneumonia with acute respiratory dis-
tress syndrome, sepsis and multi-organ failure. Some cases develop renal failure concurrently with res-
piratory failure [3]. The causative agent of MERS is a Betacoronavirus within the subfamily Coronaviri-
dae, closely related to SARS Coronavirus [4]. The spike surface glycoprotein S of MERS is responsible 
for binding to the human host cell receptor Dipeptidyl Peptidase IV, DPPIV [5], showing broad tissue 
distribution in humans (including bronchial and renal epithelia). Bat, civet, pig and rabbit DPPIV 
orthologs may support infection of corresponding cell lines, while canine, feline, rodent and chicken cells 
were found non-susceptible [6,7]. Importantly, a number of studies position the MERS-CoV spike protein 
S as a key target for virus neutralizing antibodies [8,9,10] including our own work [11]. 
Modified Vaccinia Virus Ankara (MVA) is a replication-deficient viral vector that holds great promise as 
a safe and efficacious vaccine platform. MVA can be engineered to encode one or more foreign antigens 
[12] and thus function as a multivalent vaccine, eliciting cell-based and humoral immune responses. The 
vector can be used at biosafety level 1 and has intrinsic adjuvant properties. 
Modified Vaccinia virus Ankara recombinant virus expressing Middle East Respiratory Syndrome Coro-
navirus Spike protein (MVA-MERS-S) is an experimental vaccine which has been shown to induce neu-
tralizing antibodies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV) in a range of 
animal models. Facing the human pathogenicity of MERS-CoV with case-fatality rates in the 30-
40% range and the unclear epidemiological situation of MERS in the Middle East and outside it is sug-
gested to promote early clinical studies that evaluate the tolerability and immunogenicity of the vaccine 
candidate MVA-MERS-S in humans. 
7.2 
MERS Vaccine Development and Preclinical Studies Using the MVA-MERS-S 
Vaccine Vector 
The experimental vaccine MVA-MERS-S has been studied in several animal models as outlined in the 
investigator’s brochure (IB) (13). More specifical primary pharmacology data were obtained in the fol-
lowing models and studies: 
- 
Mouse immunogenicity (Song F et al., 2013) 
- 
Protection from MERS-CoV challenge in transiently tranduced hDPPIV mice (Volz A et al., 
2015) 

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- 
Rat immunogenicity (as part of GLP compliant pivotal nonclinical toxicology study) 
- 
Dromedary camels (Haagmans BL et al., 2016) 
To date there is no appropriate non-human-primate model established for MERS, that models human 
disease in a satisfactory manner. 
Table 4 of the investigator brochure summarizes the findings in these models that collectively describe 
MVA-MERS-S as a vaccine candidate with good immunogenicity, affording protection from virus chal-
lenge in two relevant animal models (mice and camels) without significant toxicity.  
7.3 
Clinical Experience available for MVA-MERS-S 
To date, there has been no prior clinical trial experience with the MVA-MERS-S vaccine. This trial will 
be a first-in–human study for the investigational product MVA-MERS-S. 
However, ample clinical experience with the licensed MVA vaccine (Imvanex/Imvamune, Bavaria Nor-
dic, EMA licensing 2013) for protection against smallpox and multiple MVA-vaccine constructs for other 
infectious diseases (HIV, Influenza, Malaria, Tb, cancer, hepatitis C&B) is available and more than 
6,500 patients and healthy volunteers were enrolled in the clinical trials listed in table 15 [13]. The MVA 
vector has been used extensively in diverse study populations including children, cancer patients and 
HIV and other immunocompromised individuals. No vaccine-related serious adverse event (SAE) has 
been reported therein and reported adverse events (AE) were all mild-to-moderate in nature and clearly 
dose-dependent. 
All AEs reported were transient and resolved spontaneously. 
7.4 
Risk-benefit considerations 
The participation in a phase I/ FIM study may not be of a therapeutic benefit to healthy subjects. Known 
risks related to the pharmacological properties of the investigational compound and/or study modalities 
are possible. To our best knowledge and judgement, the IMP seems to be safe and no severe side 
effects and no unacceptable adverse drug reactions (ADR) are expected with this study, as the used 
MVA vaccine vector has been extensively used in clinical trials for other infectious diseases threats 
encompassing in >6500 individuals, including children, cancer patients and immunocompromised hosts. 
The vaccine vector has had an excellent safety profile and unexpected adverse reactions conferred by 
the antigenic insert are not anticipated. 
Preclinical data suggest a favorable safety and tolerability profile. All relevant preclinical studies have 
been conducted that are needed to start clinical development. Based on available information and the 
design of the study, the sponsor and the Investigator consider the trial to be ethically acceptable. The 
duration of confinement, the medical surveillance and the chosen time interval for the sequential dosing 
of each dosing cohort are considered adequate to ensure safety of the subjects. Special consideration 
was given to adequate spacing of dosing and frequent safety assessments as mandated and recom-
mended by the regulatory authorities. 
During protocol development, processes and data have been identified which are critical to ensure hu-
man subject protection and the reliability of trial results. 
7.4.1 Potential Risks for Study Participants 
7.4.1.1 
Phlebotomy 
The total amount of blood sampled from a subject will be max. 610 mL (575 mL for the safety and im-
munogenicity sampling, 35 mL for screening) over 7 months and additional 300 ml for the subjects re-
ceiving a 3rd immunization. No more than 500 mL will be drawn in 3 months. These drawn blood volumes 
should not compromise these otherwise healthy subjects, and are equivalent volumes to voluntary blood 
donations. There may be minor bruising, local tenderness, presyncopal symptoms associated with ven-
ipuncture, or phlebitis which may subsequently result in thrombosis. These events which will not be 
documented as AEs if they occur. 
7.4.1.2 
Administration of IMP (Study Vaccine) 
Serious allergic reactions including anaphylaxis may occur and for this reason subjects will be inocu-
lated in a clinical area where Advanced Life Support trained physicians, equipment and drugs are im-

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mediately available for the management of any serious adverse reactions. Participants will be ob-
served for 24 h after vaccination. Subjects will be monitored and evaluated for AEs for at least 
30 minutes after vaccination in attendance of an investigator. 
7.4.1.3 
Potential Benefits for Subjects 
The vaccine recipients may benefit from protection against future MERS outbreaks. However, this trial 
is the first administrations of MVA-MERS-S vaccine to humans. Therefore, to date the risks-benefit ratio 
remains unknown. Participants will be strongly advised to not consider themselves protected against 
MERS after vaccination at this stage of vaccine development.  
7.4.1.4 
Summary of Potential Risks for Study Participants 
In summary, preclinical data suggest a favorable safety and tolerability profile. An extensive body of 
relevant preclinical studies have been conducted that are needed to proceed to Phase I clinical testing. 
Although potential risks are known, such as Myo-/pericarditis, Vaccinia rash, eczema vaccinatum, Post-
vaccinial encephalitis, so far clinical trials on MVA have reported transient and spontaneously resolved 
adverse events and no serious ones. Based on available information and the design of the study, the 
sponsor and the PI consider the trial to be ethically acceptable. The duration of confinement, the medical 
surveillance and the chosen time intervals for the sequential dosing of the first, second and third subjects 
of each dosing cohort are considered adequate to ensure maximal safety of the subjects and have been 
established with guidance of the competent authority. Thus, taking into account the safety measures to 
minimize risks for study participants, the exposure of healthy subjects with MVA-MERS-S vaccine is 
justified since the potential risks and disadvantages for study participants are outweighed by the poten-
tial benefits for medical research, medical practice and eventually for individuals at risk of MERS. 

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8 
STUDY OBJECTIVES 
8.1 
Primary Objective 
This study is designed to assess the overall tolerability and safety of two ascending doses of the exper-
imental MVA-MERS-S vaccine (10^7 pfu and 10^8 pfu) administered to healthy subjects and to evaluate 
the reactogenicity after administration of two dosage levels of MVA-MERS-S. Subjects will be allocated 
to two different dose cohorts each receiving two vaccine injections, one at day 0 and another on day 28. 
8.2 
Primary Endpoints  
The safety, tolerability, and reactogenicity of the experimental vaccine MVA-MERS-S will be measured 
as followed: 
- 
Occurrence of solicited local reactogenicity signs and symptoms for 14 days following the vac-
cination (see Table 3) 
- 
Occurrence of solicited systemic reactogenicity signs and symptoms for 14 days following the 
vaccination (see Table 4 and Table 5) 
- 
Occurrence of unsolicited AEs for 28 days following the vaccination  
- 
Change from baseline of safety laboratory measures  
- 
Occurrence of SAEs throughout the study period 
8.3 
Secondary Objective 
- 
To evaluate the MVA-MERS-S-specific antibody responses induced by two dosage levels of 
MVA-MERS-S 
8.4 
Secondary Endpoints 
- 
Humoral immunity: Magnitude of MERS-S-specific antibody responses as assayed by ELISA 
8.5 
Exploratory Objectives 
- 
To evaluate MVA-MERS-S–specific cellular immune responses after administration of MVA-
MERS-S 
- 
To characterize MERS-S-induced B and T cell memory responses 
- 
To evaluate innate cell subset phenotypes and function induced by MVA-MERS-S 
- 
To evaluate early innate immunity gene expression signatures induced by the MVA-MERS-S  
- 
To comprehensively investigate vaccine-induced humoral immune responses and antibody 
functions 
The results from exploratory objectives may not be part of the final study report. 
9 
INVESTIGATIONAL PLAN 
9.1 
Overall Study Design and Plan: Description  
This is an open, single-center phase I dose escalation trial in 24 healthy subjects of both sexes. Subjects 
will be allocated to two different dose cohorts each receiving two vaccine injections, one at day 0 and 
another on day 28. For safety reasons, subjects will be vaccinated in both cohorts in a staggered man-
ner. Dosing of subjects will commence in dosing cohort 1 (1x10^7 pfu) followed by dosing cohort 2 
(1x10^8 pfu). Dosing of cohort 2 will not start before both vaccinations and safety assessments of the 
first dose cohort are completed. 
Second immunization and dose escalation will be performed following a review of the interim safety 
report by the Local Safety Board. 
9.2 
Discussion of Study Design, Including the Choice of Control Groups  
In close coordination with the national regulatory authorities, the study design, including doses and 
schedule has been optimized to safely investigate this first-in human vaccine candidate. The study will 

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be a single center, open label, dose escalation study of the MVA-MERS-S candidate delivered by i.m. 
injection at two dose levels. In this small study with focus on safety and tolerability, blinding was deferred 
to ensure maximal safety and transparency. 
9.3 
Selection of Study Population 
24 healthy male and female subjects, aged between 18 and 55 years will be enrolled in this clinical trial. 
The subjects will be recruited from the study center subject pool and public advertisement. Allocation to 
a certain treatment number (or subject number) will be done in successive order following screening 
and based on the subjects’ availability. 
9.3.1 Inclusion Criteria 
The subject must not be enrolled before all inclusion criteria (including test results) are confirmed. Sub-
jects meeting all of the criteria listed below will be included in the study: 
1. Ability to understand the subject information and to personally sign and date the informed con-
sent to participate in the study, before completing any study related procedures. 
2. Provided written informed consent. 
3. Healthy male and female subjects aged 18 – 55 years inclusive at the time of consent. The date 
of signing informed consent is defined as the beginning of the screening period. This inclusion 
criterion will only be assessed at the first screening visit. 
4. No clinically significant health problems as determined during medical history and physical ex-
amination and clinical laboratory results at screening visit. Following laboratory parameters 
should be within normal limits: WBC, ANC, platelets. AST, ALT and ALP should be ≤ULN, Hb≥ 
LLN, Troponin T < 2-fold ULN, urine glucose should be negative, CrCL >60ml/min, urine protein 
≤30mg/dl and total bilirubin should not exceed 1,5 x ULN. Non-clinically significant, minor devi-
ations of laboratory measurements (except for ALT, AST which must be ≤ULN, CrCl which must 
be >60ml/min and Troponin T < 2-fold ULN) can be tolerated as long as they will not increase 
the risk of the individual having an adverse outcome from participating in this study as judged 
by the investigator. Deviations of laboratory measurements from the reference ranges of more 
than grade 1 according to Common Toxicity Criteria lead to an exclusion of the subject. 
5. Body weight in defined relation to height. Body mass index 18.5 – 30.0 kg/m2 and weight >50 kg 
at screening. 
6. Non-pregnant, non-lactating female with a negative pregnancy test at screening and on day -
1/day 27. 
7. Females of child-bearing potential who agree to comply with the applicable contraceptive re-
quirements of the protocol (9.3.2.1) from at least 7 days prior to vaccination until day 56 or fe-
males who are permanently sterilized (at least 6 weeks post-sterilization). 
8. Males who agree to comply with the applicable contraceptive requirements of the protocol as 
defined above from day 0 through day 56. 
9. Be willing to refrain from blood donation during the course of the study. 
10. The subject is co-operative and available for the entire study. 
 
Additional criteria for the subjects receiving the 3rd vaccination: 
11. Males and females who agree to comply with the applicable contraceptive requirements of the 
protocol as defined above from day 0 to day 28 of the 3rd vaccination (males) and 7 days prior 
to 3rd vaccination to day 28 after the 3rd vaccination (females), respectively.   
12. Non-pregnant, non-lactating female with a negative pregnancy test on day 0 of the 3rd immun-
ization. 
 
 
9.3.2 Exclusion Criteria 
Subjects are excluded from the study if any of the following criteria are met at screening or at day -1: 

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1. Prior receipt of a MERS vaccine or MVA immunizations. 
2. Receipt of any vaccine in the 2 weeks prior to 1st trial vaccination (4 weeks for live vaccines) or 
planned receipt of any vaccine in the 3 weeks following the 2nd trial vaccination. 
3. Known allergy to the components of the MVA-MERS-S vaccine product as eggs, chicken pro-
teins, and gentamycin or history of life-threatening reactions to vaccine containing the same 
substances. 
4. Known history of anaphylaxis to vaccination or any allergy likely to be exacerbated by any com-
ponent of the trial vaccine. 
5. Participation in a clinical trial or use of an investigational product within 30 days or five times the 
half-life of the investigational drug -whichever is longer- prior to receiving the first dose within 
this study. 
6. Evidence in the subject's medical history or in the medical examination that might influence 
either the safety of the subject or the absorption, distribution, metabolism or excretion of the 
investigational product under investigation. 
7. Clinically relevant findings in ECG, in particular prolonged QTc (B) of > 450 msec in males and 
> 460 msec in females. 
8. Any positive result for HIV1/2, HCV antibody or HBs antigen testing. 
9. Any confirmed or suspected immunosuppressive or immunodeficient condition, cytotoxic ther-
apy in the previous 5 years, and/or diabetes. 
10. Subjects with inflammatory, infectious and neuroinflammatory underlying disease which could 
cause an expected impairment of the blood brain barrier such as meningitis, multiple sclerosis, 
epilepsy, or Alzheimer’s disease. 
11. Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding a single 
febrile seizure as a child. 
12. Known history of Guillain-Barré Syndrome. 
13. Active malignancy or history of metastatic or hematologic malignancy. 
14. Suspected or known alcohol and/or illicit drug abuse within the past 5 years. 
15. Moderate or severe illness and/or fever >38°C within 1 week prior to vaccination. 
16. Administration of immunoglobulins and/or any blood products within the 120 days preceding 
study entry or planned administration during the study period. Oral or parenteral immunosup-
pressant and immunomodulating agents (including interferons) should be discontinued at least 
4 weeks prior to first injection. 
17. History of blood donation within 60 days of enrollment or plans to donate within the treatment 
phase (until the 2nd vaccination). 
18. Receipt of chronic (defined as more than 14 days) immune suppressants or other immune-mod-
ifying drugs within 6 months of study inclusion (screening). 
 
For corticosteroids, this will mean prednisone, or equivalent, greater than or equal to 
0.5 mg/kg/day. 
 
Intranasal and inhaled steroids are allowed. Topical steroids are permitted provided they 
are not required to be applied to injection site. 
19. Subjects with skin lesions close to the injection site or active oral lesions will be excluded. 
20. Thrombocytopenia, contraindicating intramuscular vaccination based on investigator's judg-
ment. 
21. Subjects with a significant infection or known inflammation. 
22. History of relevant cardiovascular disorders or evidence of hyper- (sitting blood pressure systolic 
>140 or diastolic >90 mmHg) or hypotension (sitting blood pressure systolic <90 or diastolic 
<40 mmHg) at screening. 
23. Subjects who are known or suspected not to comply with the study directives. 

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24. Any other significant finding that in the opinion of the investigator would increase the risk of the 
individual having an adverse outcome from participating in this study. 
Additional criteria for the subjects receiving the 3rd vaccination: 
Receipt of any vaccine in the 2 weeks prior to (4 weeks for live vaccines) or 3 weeks following the 3rd 
vaccination.    
9.3.2.1 Reproductive Potential 
The study population includes female of child-bearing potential (FOCP). FOCP have to agree to comply 
with the applicable contraceptive requirements of the protocol as named below for the duration of the 
study or females who are permanently sterilized (at least 6 weeks post-sterilization). 
Effective contraception is defined as a contraceptive method with failure rate of less than 1% per year 
when used consistently and correctly and when applicable, in accordance with the product label for 
example: 
• 
Oral contraceptives, either combined or progesterone alone,  
• 
injectable progesterone,  
• 
implants of etenogestrel or levonorgestrel 
• 
oestrogenic vaginal ring  
• 
percutaneous contraceptive patches,  
• 
intrauterine device or intrauterine system,  
• 
male partner sterilization at least 6months prior to the female subject’s entry into the 
study, and a monogamous relationship 
• 
male condom combined with a vaginal spermicide (foam, gel, film, cream or supposi-
tory). 
• 
male condom combined with a female diaphragm, either with or without a vaginal sper-
micide (foam, gel, film, cream, or suppository) 
Condoms are to be used with the mentioned acceptable contraceptives. 
9.3.2.2 Restrictions 
Subjects will be asked to fast for at least 8 hours prior to dose administration in the morning of day 0 
and 28 until 2 hours after vaccination.  
9.3.3 Removal of Subjects from Therapy or Assessment  
The study in its entirety may be discontinued prematurely by the PI or sponsor at any time (see below), 
and/or individual subjects may terminate their participation prematurely, or have their participation be 
terminated by the Investigator. 
9.3.3.1 Withdrawal of Subject from the Study 
The following circumstances may lead to discontinuation of the study by an individual subject who will 
then be recorded as a drop-out include but are not limited to the following: 
 Withdrawal for personal reasons 
 Adverse events necessitating withdrawal from the study 
 Sudden incidence of diseases 
 Circumstances in which the health of the subject would be endangered upon continued participation 
in the study 
 Subject non-compliance with study requirements 
 An AE, which requires discontinuation of the study involvement or results in inability to continue to 
comply with study procedures 
 Significant protocol violation 
 Lost to follow up 

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 Other (must be specified) 
The reason for withdrawal will be recorded in the eCRF. If withdrawal is due to an AE, appropriate 
follow-up visits or medical care will be arranged, with the agreement of the subject, until the AE has 
resolved, stabilized or a non-trial related causality has been assigned. The Local Safety Board may 
recommend withdrawal of subjects. 
At least 3 documented attempts must be made within 2 weeks to contact any subject lost to follow-up at 
any time point prior to the last scheduled office visit. One of the documented attempts must include a 
written communication (e.g. post mail, courier) with acknowledgement of receipt requested (e.g. certified 
mail, registered mail) sent to the subject’s last known address, requesting that they return any unused 
investigational medicinal product and return to the study site for final safety evaluations. 
A replacing subject will be assigned to the same administration sequence as the drop-out and to an ID 
number which is the drop-out number plus 100 (drop-out subject number 102 means replacer number 
202). In case of drop out after first administration of study medication a final examination should be 
performed whenever possible. 
9.3.3.2 
Handling Subjects with Premature Study Discontinuation 
In the absence of a medical contraindication or significant protocol violation, every effort will be made 
by the Investigator to keep the subject in the study. If a subject has to be withdrawn, all efforts will be 
made to complete and report the trial observations as thoroughly as possible and to follow safety of the 
subject as per protocol. 
Subjects who withdraw or are withdrawn from the study prior to injection will be replaced. No follow-up 
of these subjects will be performed and no data will be analyzed. Subjects withdrawing or withdrawn 
within the first 7 days after second injection will be replaced, and their data will be analyzed in the safety 
population (see section 9.8.1.2). Subjects withdrawing or withdrawn after study day 35 will not be re-
placed, and their data will be analyzed in the safety population and the per protocol population (see 
section 9.8.1.2). 
When a subject withdraws from the study before the planned end of the study period, all investigations 
scheduled for the end-of-study visit should be performed if the subject agrees. End-of-study evaluation 
will be completed at the time of the subject’s withdrawal, with an explanation of the reason for this 
entered onto the respective “end-of-study” section of the eCRF as follows: 
 
Adverse event (specify) 
 
Death 
 
Protocol violation (specify) 
 
Medical condition (specify) 
 
Consent withdrawal, not due to AE 
 
Lost-to follow-up 
 
Other (specify) 
9.3.3.3 
Criteria for Termination of the Study (Holding Rules) 
Safety holding rules will apply throughout the entire study period. Further injections will be discussed 
with the Local Safety Board. Should a holding rule be activated, the PI will inform the sponsor. The 
sponsor has to inform the competent authorities and the ethics committee within 15 days. 
If the event(s) occur in the higher-dose cohort, the follow-up phase of the lower dose cohort will continue. 
The discontinuation of a holding rule should be communicated to all entities in the same manner and 
timeframe as described above.  
The Local Safety Board review will consider:  
 The relationship of the AE or SAE to the vaccine 
 The relationship of the AE or SAE to the vaccine dose, or other possible causes of the event 
 If appropriate, additional screening or laboratory testing for other subjects to identify those who may 
develop similar symptoms, and alterations to the current informed consent form will be discussed 

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All injected subjects will be followed for safety until resolution or stabilization (if determined to be chronic 
sequelae) of their AE. AE grading will be done according to FDA’s 2007 voluntary guidance: (14) or 
according to CTCAE v4 (15). Please refer to Table 3- Table 5 for further details. 
The holding rules are as follow: 
 Solicited (expected) local adverse events: 
o 
If more than 25% of injections (minimum 2 individuals) are followed by Grade 3 solicited 
swelling or pain or Grade 4 redness beginning within 3 days after injection (day of in-
jection and one subsequent day) and persisting at Grade 3 (swelling or pain)/4 (red-
ness) for >48 – 72 hours 
 Solicited (expected) systemic adverse events:  
o 
If more than 25% of injections (minimum 2 individuals) are followed by Grade 3 solicited 
systemic AE (or Grade ≥ 3 physical observations as defined above and in Sec-
tion 9.7.11) beginning within 3 days after study injection (day of injection and one sub-
sequent day) and persisting at Grade ≥ 3 for >48 – 72 hours 
 Unsolicited (unexpected) adverse events: 
o 
If more than 25% of subjects (minimum of 2 individuals) develop a Grade ≥ 3 unsolicited 
AE (including laboratory AE and physical observations) that is considered probably or 
definitely related to injection and persists at Grade 3 for >48 – 72 hours 
 A serious adverse event occurs that may be related to the IMP 
9.3.3.4 Study Termination 
The PI or sponsor may terminate the trial at any time. In the case of study termination, investigators will 
be informed of the procedures to be followed to ensure adequate consideration is given to the protection 
of the subject’s safety. 
The Investigator will be responsible for informing the sponsor of the trial’s termination within 24 hours. 
The sponsor has to inform the competent authorities and the ethics committee within 15 days. 
9.4 
Treatments 
9.4.1 Treatments Administered 
All eligible subjects will be allocated to one of the two dose cohorts according to the assignment list. 
Each subject will receive two or three vaccine injections administered as i.m. injections in the deltoid 
region of the upper arm muscle.  
For safety reasons dose administration in each dose level will be performed in four groups. Dose ad-
ministration for the first subject at all dose levels will be vaccinated 48 hours prior to the second groups 
(second and third subject) of this dose level. The second and the third subject will be vaccinated in an 
interval of at least 5 min and after a period of at least 48 hours after the first subject to assess for imme-
diate hypersensitivity reaction (within 60 min after the vaccination) or cytokine release (within 24 hours 
following the vaccination). The next group of four subjects can be vaccinated in parallel (in intervals of 
at least 5 min) at least 24 hours after the second group and at least 24 hours before the last group. The 
last group of the dose cohort including five subjects will be dosed on the same day in intervals of at least 
5 min. Dosing events are supervised by an Investigator.  

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Figure 1: Dose administration groups 
 
 
A Local Safety Board will be established for this study. Planned 2nd immunization and dose escalation 
will occur following a review of the interim safety report. Interim safety reports will contain safety data 
obtained until day 7.  
The second immunization for each subject will be done after the Local Safety Board reviewed individual 
safety data of the respective subject.  
All subjects who consented to the study extension will be immunized a third time with a vaccine dose of 
1x108 pfu MVA-MERS-S at 12 months (± 4 months) after the first vaccination.  
For the decision about dose escalation safety data obtained until day 7 after the second immunization 
of all subjects of the first cohort will be taken into account. 
A dose level may be repeated and furthermore, additional dose step(s) may be added but not exceeding 
dose of 1x108 pfu MVA-MERS. The decision to repeat and/or to modify the dose level and/or to add 
additional dose steps will be taken by the Local Safety Board and the Ethics Committee and Competent 
Authority will be notified.  
Repetition or modification of dose steps are only assumed for the second cohort if dose escalation is 
not possible due to safety-events observed within the lower dose cohort. Safety-events may be observed 
within the lower dose cohort that do not lead to study termination according to the holding rules but also 
do not warrant the increase of the dose up to 1x108 pfu MVA-MERS. In this case, the second cohort 
may be vaccinated with the same dose as the first cohort or a dose lower than 1x107 pfu MVA-MERS 
may be applied. 
9.4.2 Identity of Investigational Medicinal Product 
 
Name:  
 
MVA-MERS-S  
 
Dosage form: 
 
Suspension for injection in a pre-filled syringe 
  
Active substances: 
MVA-MERS-S  
Route:  
 
IM injections 
MAH:  
 
Ludwig-Maximilians-Universität München 
 
Additional information can be found in the Investigator’s Brochure [13]. 
9.4.2.1 Labeling 
The study vaccine will be provided by IDT Biologika GmbH, Dessau to CTC North, and will be labeled 
in accordance with§ 5 GCP-V. 
9.4.2.2 Packaging 
Sponsor will provide study vaccine for this study. Investigational medicinal product will be provided in 
glass vials. These containers are suitable for the purpose and ensure the stability of the investigational 
medicinal product. 

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9.4.2.3 Storage 
The investigator has overall responsibility for ensuring that study medication is stored under appropriate 
conditions in a secure, limited-access location. Study medication is distributed by a nominated member 
of the study team. 
Study medication must be stored in accordance with labeled storage conditions (≤ -20°C). Temperature 
monitoring is required at the storage location to ensure that the study medication is maintained within 
an established temperature range. The temperature is monitored such that at least minimum and max-
imum temperature values throughout the total duration of the study are recorded and records are main-
tained. 
The sponsor must be notified of any excursion from the established range. Relevant temperature excur-
sions will require site investigation as to cause and remediation. The sponsor will determine the ultimate 
impact of excursions on the investigational medicinal product and will provide supportive documentation 
as necessary. 
9.4.2.4 Shipment 
The investigational medicinal products will be provided by the sponsor in sufficient quantity. The address 
for delivery purposes is: 
CTC North GmbH & Co. KG 
am Universitätsklinikum Hamburg-Eppendorf 
Martinistr. 64 
20251 Hamburg, Germany 
The batch number of the IMP used in the study will be given in the study report.  
9.4.2.5 Drug Accountability 
The PI has the overall responsibility for administering the investigational medicinal products. The IMP 
must be administered in the manner specified in the study protocol and the pharmacy manual. 
The PI or an authorized member of the study team will acknowledge receipt of the study medication 
documenting shipment content and condition. Damaged supplies will be replaced. Accurate records of 
all study medication received, dispensed, used, returned or destroyed must be maintained. No study 
medication may be destroyed or returned from the investigational site without prior knowledge and writ-
ten consent by the sponsor. If such transfer is authorized by the sponsor, all applicable local, state and 
national laws must be adhered to for the transfer. 
An Investigator will administer the investigational medicinal products. All administrations will be docu-
mented in the site’s drug accountability log or other study drug record.  
The sponsor or its representatives must be permitted access to review the supplies storage and distri-
bution procedures and records. 
At the end of the study or as instructed by the sponsor all unused stock and empty used boxes are sent 
to a nominated contractor or will be destroyed on behalf of the sponsor. Study medication being returned 
or destroyed must be counted and verified by clinical investigational site personnel and the sponsor or 
designee. All certificates of delivery/drug receipts should be signed by the site representative to confirm 
contents of shipment. Shipment return forms must be signed prior to shipment by CTC North. The spon-
sor must give authorization to return or destroy any study medication prior to shipment or destruction. 
Shipment of all returned study medication must comply with local, state, and national laws. 
Based on the entries in the site drug accountability logs, it must be possible to reconcile study medication 
delivered with those used and returned. One hundred percent of the study medication must be ac-
counted for and all discrepancies investigated and documented. 
9.4.2.6 Subject Compliance 
For study medication administration at CTC North, compliance must be assessed by observation of 
dosing. Details will be recorded on the drug accountability log or other appropriate source documents. 
9.4.3 Preparation and Administration 
Study medication will be provided in glass vials for administration with conventional syringes. Instruc-
tions for storage, preparation, administration, and destruction of study medication are presented in the 
pharmacy manual. 

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The vaccine will be injected intramuscularly into the deltoid region of the upper arm muscle.  
The vaccine must not be administered to subjects allergic to the active substance, to any of the excipi-
ents, to eggs, chicken proteins, and gentamycin or with a history of life-threatening reactions to the study 
vaccine containing the same substances. Vaccine must not be administered to subjects with febrile 
illness or acute infection. 
The study personnel must clean the site on injection with a suitable antiseptical and let the antiseptical 
evaporate before vaccination. 
Subjects must be kept under observation by authorized members of the study team for 24 hours after 
vaccination to ensure their safety. Any reactions reported during observation period will be documented. 
9.4.4 Method of Assigning Subjects to Treatment Groups 
Subjects willing and eligible to participate in this study will be assigned to a treatment cohort according 
to the assignment list. Assignment to the 2nd dose cohort will start after all subjects for the 1st dose cohort 
are enrolled. The detailed process of subject identification and assignment of subject numbers can be 
found in section 9.4.10.2. No randomization is planned for this study. 
9.4.5 Selection of Doses in the Study 
The doses selected in this study represent immunogenic dose levels as observed in prior clinical trials 
using MVA-vector-based vaccines. 
9.4.6 Selection and Timing of Dose for Each Subject  
All dosing events will occur between 8:00 h and 14:00 h. 
9.4.7 Blinding  
As this is an open-label study, no blinding procedures are necessary. 
9.4.8 Prior and Concomitant Therapy 
As only healthy subjects will be enrolled, concomitant use of any medicinal product is forbidden prior to 
dosing as defined in section 9.3.2 Exclusion Criteria of this protocol. Prior to the dosing, subjects will be 
asked about this point.  
Any use of drugs will be documented specifying the substance, dose, time and reason for use. 
9.4.9 Rescue Medication 
For symptomatic management of flu-like symptoms, the use of anti-pyretic drugs (e.g. paracetamol/ibu-
profen) within the daily recommended dosage will be allowed after consultation of the investigator. 
9.4.10 Treatment Compliance  
9.4.10.1 
Admission to the study 
Admission to the study will be effective upon the subject's arrival at the study ward. A subject will only 
be admitted to the study if all inclusion and none of the exclusion criteria are met. Should there be any 
doubts as to the state of health, a subject will not be admitted to the study.  
Subjects who fail to make themselves available upon commencement of the study or who cannot par-
ticipate for personal reasons will be considered as not admitted to the study. These will be replaced by 
back-up subjects who will be recruited in surplus. 
9.4.10.2 
Subject Identification 
Screening numbers are to be assigned sequentially to all subjects as they consent to take part in the 
study. This will be a 3-digit number starting at 001. The subject number is assigned to subjects when 
they are enrolled into the study and according to appearance of the subjects. This will be a 3-digit num-
ber starting at 101. For screening failures, the screening number will be the identifying number used 
throughout the documentation. Subjects, who will replace a subject e.g. a withdrawn subject, will receive 
a screening number according to the above described scheme. In difference to the described subject 
number assignment, replacement subjects will receive a 3-digit subject number which will consist of the 
old subject number (of the subject which should be replaced) plus 100.  

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Allocation to a certain subject number will be done in successive order following screening and based 
on the subjects’ availability.  
The investigator will keep a record relating the subject numbers and the names of all subject (including 
the CTC North identification number) that have given their informed consent, to allow easy checking of 
data in subject files, when required. This record will also include the date of subject’s enrolment and 
completion, as well as subjects who could not be included in the study for whatever reason. 
9.4.10.3 
Screening, Confinement and Ambulatory Visits  
9.4.10.3.1 Confinement (Day -1 to Day 1 and Day 27 to Day 29) 
The Subjects will be admitted to the study ward in the evening on Day -1 going through regular check-
in procedures including an ID check, vital signs, an inclusion/exclusion check, an alcohol breath test and 
a urine drug, and pregnancy test. The Subjects will stay on the ward until the morning of Day 1 experi-
encing blood draws for immunogenicity analysis, documentation of occurrence of any injection site re-
action, systemic events/reaction and adverse event questioning throughout the confinement period. 
Subjects will be dismissed at the earliest after the 24 h after vaccination and after subjects were trained 
on the use of the diary.  
This schedule will be repeated in for the second vaccination on day 27 to day 29.  
9.4.10.3.2 Screening  
At the screening visit the following interventions will be performed: 
 
Informed Consent 
 
I/E Criteria 
 
Medical History/ Demographics 
 
Physical Examination 
 
Vital Signs/Temperature 
 
ECG 
 
Height and Weight 
 
Alcohol Breath Test 
 
Urine Drug Screen 
 
Urine Pregnancy Test 
 
HIV/HBV/HVC Serology 
 
Safety Laboratory (Urine/Blood) 
 
Troponin T 
9.4.10.3.3  Confinement Day -1 to Day 1 and Day 27 to Day 29 
During confinement the following interventions will be performed: 
 
I/E Criteria check 
 
Update medical history  
 
Targeted physical examination 
 
Vital signs / Temperature 
 
12-lead ECG (only on day 28) 
 
Injection Site reaction & systemic events/reaction assessment 
 
AE/ConMed 
 
Alcohol Breath Test 
 
Urine Drug Screen 

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 
Serum Pregnancy Test 
 
Safety Laboratory (Urine/Blood) 
 
Blood sampling for humoral immunogenicity 
 
Blood sampling for cellular response  
 
PBMC freezing and plasma aliquots 
 
Blood sampling for RNA storage (only on day 0, 1, 28, 29) 
 
Blood sampling for troponin (only on day 28) 
 
Blood sampling for innate immunity (only on day 0, 1, 28 and 29) 
 
Training on subject diary 
 
Collection and review of diary 
 
After dosing the following events will be performed at 2 h, 4 h, 6 h, 8 h, 12 h, 24 h: 
 
Vital signs (and at 0 h, before dose administration) 
 
Temperature (and at 0 h, before dose administration) 
 
(AE)/ConMed (and at 0 h, before dose administration) 
 
Injection site reactions & systemic events/reactions assessment 
9.4.10.3.4  Ambulatory Visits 
Subjects will return to the study ward for ambulatory visits on study day 3, 7 and 14 (±2), after the first 
vaccination and on study day 35, 42 (±2), 56 (±3), 84 (±3) after the second vaccination. 
On the ambulatory visits the following events will be performed: 
 
Targeted Physical Examination (only on day 42) 
 
Vital signs/ Temperature 
 
12-lead ECG (only on day 7, 14, 35, 42) 
 
Injection Site reaction & systemic events/ reaction assessment (only on day 3, 7, 14, 35 and 42) 
 
Safety Laboratory (Urine) (only on day 7, 14, 35, 42) 
 
Safety Laboratory (Blood) (only on day 3, 7, 14, 35, 42) 
 
Blood sampling for troponin (only on day 7, 14, 35, 42) 
 
Blood sampling for humoral immunogenicity (only on day 7, 14, 35, 42, 56, 84) 
 
Blood sampling for cellular response (only on day 14, 42, 56, 84) 
 
PBMC freezing and plasma aliquots  
 
Blood sampling for RNA storage (only on day 3, 7, 35) 
 
Blood sampling for innate immunity (only on day 3, 7, 35) 
 
Adverse events assessment 
 
Concomitant medication assessment 
 
Collection and review of diary 
9.4.10.3.5  Ambulatory vaccination and subsequent ambulatory visits (only for subjects who 
gave consent to the study extension) 
Subjects will return to the study ward for an ambulatory vaccination visit 12 months (±4 months) after 
the first immunization. 
 
The following interventions will be performed:  

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 
Informed Consent 
 
I/E Criteria check 
 
Update medical history  
 
Weight 
 
Physical examination 
 
Vital signs / Temperature 
 
12-lead ECG  
 
Injection Site reaction & systemic events/reaction assessment 
 
AE/ConMed 
 
Alcohol Breath Test 
 
Urine Drug Screen 
 
Urine Pregnancy Test 
 
Safety Laboratory (Urine/Blood) 
 
Blood sampling for humoral immunogenicity 
 
Blood sampling for cellular response  
 
PBMC freezing and plasma aliquots 
 
Blood sampling for RNA storage  
 
Blood sampling for troponin  
 
Blood sampling for innate immunity  
 
Dosing 
 
Training on subject diary 
 
After dosing the following events will be performed at 2 h, 4 h and 6 h: 
 
Vital signs (and at 0 h, before dose administration) 
 
Temperature (and at 0 h, before dose administration) 
 
(AE)/ConMed (and at 0 h, before dose administration) 
 
Injection site reactions & systemic events/reactions assessment 
 
Subjects will return to the study ward for ambulatory visits on study day 1, 3, 7 and 14 (±2), after the 
third vaccination. 
On the ambulatory visits the following events will be performed: 
 
Vital signs/ Temperature 
 
Injection Site reaction & systemic events/ reaction assessment 
 
Safety laboratory (urine) (only on day 7, 14) 
 
Safety laboratory (blood) 
 
Blood sampling for humoral immunogenicity (only on day 7, 14) 
 
Blood sampling for cellular response (only on day 7, 14) 
 
PBMC freezing and plasma aliquots  
 
Blood sampling for RNA storage (only on day 1, 3, 7) 
 
Blood sampling for innate immunity (only on day 1, 3, 7) 

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 
Adverse events assessment 
 
Concomitant medication assessment 
 
Collection and review of diary 
 
9.4.10.3.6 End of study/ Early termination visit 
An end-of-study follow-up visit will be performed on day 180 (±7). The following interventions will be 
performed:  
 
Physical examination 
 
Vital signs/Temperature 
 
Weight 
 
AE/ConMed 
 
Urine pregnancy test 
 
Safety Laboratory (Urine and Blood) 
 
Blood sampling for Troponin T 
 
Injection site reactions & systemic events/reactions assessment 
 
Collection subject diary  
 
Blood sampling for humoral immunogenicity 
 
Blood sampling for cellular response 
 
PBMC freezing and plasma aliquots 
 
For subjects receiving 3 vaccinations, an additional end-of-study visit will be 28 (±2 days) after the 3rd 
vaccination. The following interventions will be performed: 
 
Vital signs/Temperature 
 
AE/ConMed 
 
12-lead ECG 
 
Urine pregnancy test 
 
Safety laboratory (urine and blood) 
 
Blood sampling for Troponin T 
 
Injection site reactions & systemic events/reactions assessment 
 
Collection of subject diary  
 
Blood sampling for humoral immunogenicity 
 
Blood sampling for cellular response 
 
PBMC freezing and plasma aliquots 
 
9.4.10.4 
Early Termination 
All enrolled subjects who complete the study, discontinue early, or withdraw from the study will have the 
follow-up assessments and procedures completed for their safety as outlined in Table 1. Subjects who 
discontinue early or withdraw from the study will be replaced if they discontinue early or withdraw up to 
day 35. 
In some cases it may be necessary for subjects to return to CTC North for additional care, confinement, 
and/or follow-up. Circumstances in which this may be necessary are:  

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 
Follow-up on abnormal laboratory evaluations 
 
Follow-up on an ongoing AE at the final visit 
 
All additional safety follow-up visits will be at the discretion of the investigator and the sponsor. 
9.5 
Study Procedures and Examinations 
Details regarding scheduled assessments and procedures to be conducted in this study are provided 
below. For detailed assessment of schedules refer to Table 1. 
All relevant Laboratories involved in this trial work according to GLP. Continuous GLP compliance 
throughout the trial is assured. 
9.5.1 Screening Procedures 
Written, signed, and dated informed consent from the subject prior to the performance of any study 
related procedures must be obtained by an Investigator. Subjects will first have ample time to read the 
subject information before an investigator will start the information and informed consent process. The 
subject information/ informed consent process will be performed according to CTC North SOPs in 
groups of 2-5 subjects. Investigator will provide the subjects with information of the study and explain 
the nature of the study point by point. During this verbal subject information process subjects have 
already the opportunity to ask questions. After that, the subjects have the opportunity to individually ask 
questions in a one-to-one meeting with the Investigator. If the Investigator is convinced that the subject 
understands the nature and risks of the trial, and each subject had ample time for consideration and 
formulation of questions (which could also mean that the subjects first discuss the decision with friends 
or family members), and if all questions are answered the subject will asked to personally sign the in-
formed consent form. A copy or a second original of the signed informed consent form must be given to 
the subjects for their records. 
Screening procedures must be completed between 28 days and 2 days prior to receiving the first dose 
of study medication. See Table 1 for a complete list of screening procedures to be performed. 
Only an authorized and trained investigator may decide on the eligibility of the subject. 
9.5.1.1 Screening Failure  
A screening failure is defined as a subject who has given informed consent and failed to meet at least 
one inclusion criteria or met at least one exclusion criteria or has not been administered IMP as defined 
by the protocol. 
Eligible subjects who meet all inclusion and no exclusion criteria but are unable to participate in the 
study due to scheduling conflicts/timing will not be considered screening failures. 
9.5.1.2 Re-screening of Subjects 
Subjects who fail to meet all inclusion criteria or meet any exclusion criterion will not be permitted to be 
re-screened. Screening failures will not be enrolled into the study or receive IMP and cannot be re-
screened for the study at any point. 
Eligible subjects who meet all inclusion and no exclusion criteria but are unable to participate in the 
study due to scheduling conflicts/timing may be re-screened based on investigator’s discretion and 
sponsor’s approval should their availability to participate fall outside the screening window. In these 
cases, a new screening number must be assigned for each subject to be re-screened and a new in-
formed consent form signed to confirm consent for study participation. 
9.5.2 Study Examinations 
Assessments are to be performed according to the schedule shown in Table 1 and Table  and depend 
on time point of IMP administration. 
9.5.2.1 Safety 
Safety will be evaluated by collecting reported adverse events at regular intervals throughout the study 
and by the assessment of physical examination findings, vital signs, clinical laboratory parameters, 
ECGs, and adverse events.  

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9.5.2.2 Medical and Medication History 
A complete medical and medication history as well as demographic information will be assessed at the 
time-points indicated in Table 1.  
The medical history will be reviewed and recorded, including: 
Medical and Medication History 
 
Recent ingestion of medication (30 days prior to entering the screening period) 
 
History of respiratory, cardiovascular, renal, gastrointestinal, hepatic, endocrine, hematological, 
neurological, psychiatric, musculoskeletal and other diseases. 
Demographic information 
 
Date of Birth 
 
Sex 
9.5.2.3 Physical Examination  
A complete physical examination will be performed at the time points described in Table 1. 
The physical examination will include a review of the following body systems:  
 
General appearance 
 
Skin 
 
Head, Eyes, Ears, Nose and Throat  
 
Spine/Neck/Thyroid 
 
Musculoskeletal 
 
Respiratory 
 
Cardiovascular 
 
Neurological 
 
Abdomen (including liver and kidneys). 
Any abnormalities or changes in intensity from the screening visit noted during the review of body sys-
tems have to be documented in the medical record. Clinically significant abnormal findings discovered 
during a physical examination after screening will be documented either as part of medical history (sub-
ject forgot to mention an intermittent medical condition at screening) or documented as an Adverse 
Event or part of an Adverse Event (up from the time after dose administration), if the discovered symp-
tom is leading to a diagnosis. 
9.5.2.4 Electrocardiogram 
A 12-lead ECG will be done at the time points described in Table 1. Actual ECG assessment times will 
be documented. 
Subjects must be resting in a supine position for at least 5 minutes prior to collecting the ECG. At a 
minimum, the date and time of when the event was performed, the investigator’s assessment and the 
heart rate, RR, PR, QT, and QRS intervals are to be collected. All clinically significant abnormalities will 
be recorded on the appropriate source documents. 
9.5.2.5 Vital Signs 
Blood pressure should be determined by cuff (using the same method and in the same position through-
out the study). Measurements of vital signs (systolic and diastolic blood pressure as well as pulse rate) 
will be performed after the subject has been in a sitting position for at least 5 minutes at the time points 
specified in Table 1. Actual vital sign assessment times will be recorded. 
All measurements of vital signs must be recorded in the appropriate source documents. 
Any vital sign assessment that deviates from the scheduled assessment time set forth in the protocol 
will be considered a protocol deviation. 
Deviations from vital signs measurements are allowed as follows:  

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± 30 minutes (for vital sign measurements on day 0, 1, 28 and 29 and day 0 for the 3rd vac-
cination)  
9.5.2.6  
Temperature 
Temperature will be measured using a digital thermometer (orally at the time points specified in Table 
1). 
9.5.2.7 Height and Weight 
Measurements of height and weight will be performed according to the schedule in Table 1. 
Height is measured in centimeters (cm) and weight is measured in kilograms (kg). Measurements are 
to be taken in light clothing and socks (without shoes) with pockets emptied. The subject’s height is 
recorded to the nearest cm and weight is recorded to the nearest 0.1 kg. 
Height and weight will be measured and used to calculate the BMI using the following formula: 
BMI = 
 
9.5.2.8 Clinical Laboratory Evaluations 
All laboratory assays will be performed according to the laboratory’s normal procedures. Reference 
ranges will be supplied by the laboratory and used to assess the laboratory data for clinical significance 
and out-of-range pathological changes. The Investigator should assess out-of-range laboratory values 
for clinical significance, indicating if the value(s) are not clinically significant (NCS) or clinically significant 
(CS). Abnormal laboratory values that are unexpected or not explained by the subject’s clinical condition 
may be, at the discretion of the Investigator or sponsor, repeated until confirmed, explained, or resolved 
as soon as possible.  
 
The following laboratory assessments will be performed:  
9.5.2.8.1 
Bio-Chemistry 
Blood samples (4.9 mL) for serum biochemistry will be collected into a lithium heparin separator tube at 
the time points described in Table 1. The following parameters will be assessed:  
Sodium 
Aspartate transaminase (AST) 
Potassium 
Alanine transaminase (ALT) 
Calcium 
Alkaline phosphatase (ALP) 
Urea 
Gamma glutamyl transferase (GGT) 
Creatine kinase (total) 
Total bilirubin 
Albumin 
Glucose  
Total protein 
Pancreas specific amylase 
Creatinine 
Lactate dehydrogenase (LDH) 
Creatinine clearance (MDRD) (only at 
Screening) 
C reactive protein (CRP) 
9.5.2.8.2 
Hematology 
A 2.7 mL sample of blood will be drawn into a tube containing potassium ethylene diamine tetra-acetic 
acid (EDTA) anticoagulant at the time points described in Table 1. The following parameters will be 
assessed: 
Hemoglobin 
Mean corpuscular hemoglobin concentration (MCHC) 
Hematocrit 
White blood cell (WBC) count; total and differential 
Red blood cells (RBC) 
Neutrophils 
Mean corpuscular volume (MCV) 
Lymphocytes  
2
])
[
(
]
[
m
height
kg
weight

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Monocytes  
Platelet count 
Eosinophils 
Mean corpuscular hemoglobin (MCH) 
Basophils 
Reticulocytes 
 
9.5.2.8.3 
Safety Urinalysis 
The following parameters will be analyzed in fresh midstream urine. 
pH 
Ketones 
Specific gravity 
Bilirubin 
Protein 
Blood 
Glucose  
 
Microscopic examination will be conducted if blood is detected during urinalysis. The microscopic ex-
amination will comprise of RBC, WBC, casts, and bacteria.  
9.5.2.8.4 
 Urine Pregnancy Test 
In all female participants a urine beta-HCG test will be performed on fresh midstream urine at screening 
and on day 180. 
9.5.2.8.5 
 Serum Pregnancy Test 
A 7.5 mL sample of blood will be drawn into a Serum Monovette and the following parameter will be 
assessed at the time points described in Table 1: 
ß-HCG 
 
 
9.5.2.8.6 
Cardiac biomarker 
A 4.9 mL sample of blood will be drawn into serum separator tube (Z-Gel) at the time points described 
in Table 1. The following parameters will be assessed. 
 
Troponin T 
 
9.5.2.8.7 
Serology 
During the screening period only, two blood samples of approximately 7.5 mL will be drawn into a serum 
separator tube (Z- Gel) to test for the presence of HIV, Hepatitis B and C: 
HIV antibody (HIV I and HIV II) 
HCV antibody screen 
HBsAg 
 
 
9.5.2.8.8 
Drug and Alcohol Screen 
An alcohol breath test and urine screen for drugs of abuse will be performed at the time points described 
in Table 1. Additional drug and alcohol screens may be performed at the investigator’s discretion. 
Urine samples are to be tested for the following: 
Methadone (MTD) 
Barbiturates 
Benzodiazepines 
Tricyclic Antidepressants (TCA) 
Cocaine 
Morphine 
Amphetamine/Methamphetamine (MET) 
Tetrahydrocannabinol (THC) 
Ecstasy 
 
 

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9.5.2.8.9 
 Reactogenicity 
To assess reactogenicity after each immunization body temperature and reaction are recorded for at 
least 14 days after vaccination or until any symptoms resolved if longer. According to the defined time 
frame of ±2 days for the ambulatory visit on day 42 recording might be shortened to day 40. During 
confinement at the study ward temperature and solicited injection site and systemic reactions will be 
assessed and recorded by a designated member of the study team. After dismissal subjects are asked 
to maintain a diary to record daily temperature and solicited (expected) injection site and systemic reac-
tions for 14 days after each dosing. Subjects will be asked to maintain a second diary for another 14 days 
to record medicinal events. As described above, the second diary after the second immunization should 
be maintained at least until day 40. Subjects will be trained on the thermometer and diary use.  
The following items will be recorded:  
 
Daily temperature (incl. the method by which it was taken) 
 
Daily measurement of intensity grade of all other solicited (expected) injection site and sys-
temic reactions 
 
Action taken for each recorded event (none, medication taken, physician consulted, hospi-
talization) 
9.5.2.8.10  Local Reaction Assessments 
Local reactions, resulting from the IMP, will be graded using a local reaction assessment scale 
Grade Description: 
 
0 = None 
 
1 = Mild macular or papular eruption, erythema, or induration that is asymptomatic or 
mildly symptomatic. 
 
2 = Moderate macular or papular eruption, erythema or induration with pruritus, mild blis-
tering or other associated moderate symptoms. 
 
3 = Severe ulceration, superinfection, severe blistering, or phlebitis. 
 
4 = Potentially life-threatening necrosis of the skin. 
9.5.2.8.11  Adverse and Serious Adverse Events Assessments 
Subjects will be questioned in a general way to ascertain if AEs have occurred (e.g. “Have you had any 
health problems since the last time you came to the clinic/since you were last questioned?”). This open, 
standardized questioning should be done discretely in order to prevent subjects from influencing each 
other. Spontaneous reports of AEs will also be recorded as well as AEs that are observed by the inves-
tigator or a staff member.  
All AEs will be reviewed, confirmed, and classified by a qualified, designated physician. 
9.5.3 Pharmacodynamic Measurements 
Detailed information about blood sampling and processing of the samples are defined in the safety/lab 
manuals. 
9.5.3.1 Immunogenicity Assays 
The information on the blood volume drawn for immunogenicity assays given below refer to maximum 
amounts. Details on the exact blood volume are specified in the laboratory manual. 
9.5.3.1.1 
Enzyme-Linked Immunosorbent Assay (ELISA) 
To identify binding MVA-MERS antibody responses induced by the candidate vaccine ELISA assays 
will be performed on serum samples (7.5 mL serum tube) drawn at the time points described in Table 
1. The analysis will be performed at the Institute for Virology in Marburg, Germany according to the 
process defined in the Safety/ Laboratory Manual. Seroconversion will be defined as at least a two-fold 
rise in titers, or becoming seropositive in originally seronegative subjects. 
9.5.3.1.2 
Neutralization Assay 
Neutralization antibody responses against MVA will be measured on the same serum sample used for 
ELISA (7,5 mL serum tube) obtained at the time points described in Table 1 using a luciferase based 

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assay in HeLa or DF-1 cells. The analysis will be performed at the Institute for Virology in Marburg, 
Germany according to the process defined in the laboratory manual. 
9.5.3.1.3 
T cell IFN-γ ELISPOT 
The magnitude, kinetics and epitope targets of MVA-MERS T-cell responses will be assessed by IFN-γ 
ELISpot assay. The assay will be performed on cryopreserved PBMC samples (from 4 x 9 mL EDTA 
tubes) obtained at the time points described in Table 1. The analysis will be performed in the Virus-
Immunology Research Laboratory, Heinrich-Pette-Institute, Hamburg, Germany according to the pro-
cess defined in the Laboratory Manual. 
Blood samples (36 mL) for T cell immunogenicity analysis (2 x 9 mL for EliSpot and 2 x 9 mL for ICS) 
will be drawn by direct venipuncture into four EDTA tubes, capped and mixed by inversion (x3) The 
actual time that the sample was obtained will be recorded on the source documents. After applying a 
tourniquet, venous blood will be taken with a disposable needle.  
The labels will contain the following information: 
Study Number 
Study Day and Time point 
Subject Identifier  
9.5.3.1.4 
Sample preservation for Intracellular Cytokine Staining for MERS-S-specific CD4 
and CD8 T cell responses  
The magnitude and kinetics of MERS-S-specific CD4 and CD8 T-cell responses will be determined from 
cryopreserved PBMC at the time points described in Table 1 using flow cytometry (from 2 x 9 mL EDTA 
tubes as above). The analysis will be performed by Prof. Addo’s and Dr. Schulze zur Wiesch’s group at 
the UKE, hosted in the Virus-Immunology Research Laboratory, Heinrich-Pette-Institute, Hamburg Ger-
many according to the process defined in the Laboratory Manual. 
9.5.3.1.5 
Sample preservation for RNA analysis 
In the exploratory translational research program gene expression analysis from whole blood (2.5 mL 
Paxgene tube) will be performed at baseline and early time points post-vaccination to investigate early 
innate immunity gene signatures induced by the vaccine candidate and their impact on adaptive B and 
T cell immunity. 
9.5.3.1.6 
Innate immunity 
To evaluate early innate immunity gene expression signatures cryopreserved PBMC at the time points 
described in Table 1 will be analyzed using flow cytometry (from 2 x 9 mL EDTA tubes). Furthermore, 
plasma obtained after centrifugation of the EDTA tube will be analyzed via luminex multiplex assays. 
9.5.3.1.7 
Isolation of antigen-specific B cells 
Cryopreserved PBMC will be shipped to Prof. Florian Klein at the University of Cologne for the isolation 
of MERS-S specific B cells using flow-cytometry. 
9.5.3.2 Shipment of Immunogenicity Samples 
All samples, along with the corresponding documentation, will be transported from the CTC North to 
the Heinrich-Pette Institute, Leibniz Institute for Experimental Virology (AG Addo), UKE campus, build-
ing N 63 for further processing. 
After processing frozen serum samples for MVA-MERS antibodies will be shipped from there to the 
Institute of Virology in Marburg (Prof. Stephan Becker): 
Institute for Virology 
Philipps University Marburg 
Hans Meerweinstr. 2 
35043 Marburg, Germany 
Phone:   
+49 6421 2866253 
 
Fax:  
 
+49 6421 2868962 
 
Mobile:  
+49 171 5559148 
 
Email:   
becker@staff.uni-marburg.de 

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After processing frozen PBMC samples for MVA-MERS B cells will be shipped from there to the labor-
atory for experimental Immunology (Prof. Florian Klein): 
Labor für Experimentelle Immunologie 
Klinik I für Innere Medizin 
Zentrum für Molekulare Medizin 
Universität zu Köln 
Robert-Koch-Str. 21, Gebäude 66,  
50931 Köln 
Phone:  
+49 221 478 89693 Email 
 
Email:  
florian.klein@uk-koeln.de  
9.5.3.3 Samples for cellular response and exploratory translational samples 
Samples, along with the corresponding documentation, will be transported from the CTC North to: 
Prof. Marylyn Addo, UKE Emerging Infections 
 
Heinrich Pette Institute, UKE Campus, Building N 63 
Martinistr. 52 
 
20251 Hamburg, Germany 
Shipment and storage procedures are defined in the Laboratory Manual. 
9.5.3.4 Future Use of Stored Samples  
Left over blood samples may be used in the further evaluation of an adverse event or for the subsequent 
evaluation of additional parameters that are identified as important to the evaluation of an individual 
subject or to the study, or for further research regarding the immune response to the MVA-MERS vac-
cine. Any unused part of the blood samples will be securely stored in Prof. Addo’s laboratory for up to 
15 years. Parts of the blood samples may pseudonymized be shipped to collaborators for further eval-
uation. 
9.5.3.5 Safety Variables  
Assessment of safety is performed for the safety set. Safety data include: 
 
Adverse events (including changes from baseline in physical examination findings)  
 
Clinical laboratory results  
 
Vital signs  
 
12-lead ECGs  
The safety evaluation will be based upon the review of the individual values (potentially clinically im-
portant abnormalities) and descriptive statistics (summary tables, graphics) (see section 9.8).  
9.5.3.5.1 
Adverse Events 
The adverse events will be listed per subject using MedDRA terminology (preferred term and system 
organ class) and will be reported in tables summarizing the frequency of subjects with adverse events 
and adverse events by dosage level, by dose level and injection and by body system, the number of 
adverse events and number of subjects with adverse events by dosage level, by dosage level and in-
jection, and the characteristics of adverse events. 
For the hematology, clinical laboratory and the urine analysis deviations from the reference ranges will 
be summarized in frequency tables. 
9.5.3.5.2 
Clinical Laboratory 
All relevant clinical variables obtained during screening, treatment phase or final examination will be 
reported in appropriate tables together with descriptive statistics. Clinical laboratory findings outside of 
the reference range will be flagged. 
9.5.3.5.3 
Vital Signs 
For blood pressure and pulse rate descriptive statistics will be listed by sampling times (screening and 
follow up) according to the data reported in the source documents. 

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9.5.3.5.4 
ECG 
The results of the 12 lead ECG will be listed by sampling times (screening and follow up) according to 
the data reported in the source documents. 
9.5.4 Pharmacogenetic Measurements 
No pharmacogenetic measurements will be performed in this trial. 
9.6 
Data Quality Assurance 
9.6.1 Quality Assurance System 
Standard operating procedures are available for all activities relevant to the quality of the study. All 
phases of the study may be subject to audits by the quality assurance unit (QAU) of the study center. 
Results of these audits as well as any objections will be reported directly to the management. The QAU 
will issue a certificate on their activities. 
9.6.2 Monitoring 
An assigned and qualified clinical monitor may at any time demand information on the progress of the 
study by phone or in writing, or may visit the study center in order to review the original investigator 
folder and subject documents. 
Due to the nature of the study (phase I, first in human) a monitoring width of 100% of the subject and 
investigator folder documents is deemed necessary to ensure subject safety and data integrity. 
For this purpose a study monitor will review the investigator folder for completeness and verify the eCRF 
data against the source documents during frequent regular on site monitoring visits (source data verifi-
cation (SDV)). The study monitor will point out any discrepancies between source data and the data 
captured in the eCRF. The monitor will issue electronic queries to site staff to initiate discrepancy reso-
lution. Discrepancies which require eCRF data corrections have to be resolved by authorized site per-
sonnel by answering these monitoring queries. 
Further details of the monitoring procedures will be described in a study specific monitoring plan. 
9.6.3 Documentation and Data Collection 
An electronic case report form (eCRF) will be used to report all clinical data required by the protocol.  
Source documents (either paper or electronic files) will be used to collect and document at least the 
data required for transfer into the eCRF. During initial data collection, the study staff enters the infor-
mation directly into these source documents. All entries on paper documents must be clearly legible and 
signed by the person who made the entry.  
Next, site staff will transfer the study data from the source documents into the eCRF. All eCRFs will be 
checked for completeness and electronically signed by an investigator in order to ensure data entry 
accuracy. 
Corrections to study documents will be dated and initialed. Reasons for the corrections will be given if 
deemed necessary. Corrections to eCRF entries must be electronically tracked. The date on which the 
correction was performed and the person will be automatically recorded by the system's audit trail. 
9.6.4 Data Management 
Data management will double check all eCRF entries as defined in the DMP. Quality control and data 
validation procedures such as programmed automatic edit and consistency checks ensure data validity 
and accuracy immediately at the point of entry into the clinical database. The database application which 
is used to capture electronic study data is fully CFR part 11 compliant. Thus, it is access restricted, 
demands electronic signatures, maintains an electronic audit trail and provides appropriate backup func-
tionalities. Details of the application and eCRF configuration and all further data management proce-
dures will be described in the data management plan (DMP). 
The database will only be locked after all queries and discrepancies that may occur during data entry 
are resolved. 
Upon request safety reports and interim analysis will be generated and provided to the respective mem-
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After database lock, the data in the study data base will be exported and SAS datasets will be compiled 
for statistical analysis. The data will be exported in SAS transport files or other SAS-compatible format 
and transferred electronically to the responsible biometrician for statistical analysis. The locked SAS 
database will be used to generate the subject listings, tabulations, and analyses. 
9.6.5 Archival of documents 
CTC North will maintain the trial documents and take measures to prevent accidental or premature 
destruction of these documents. 
All documents related to the study will be retained until at least 15 years after the end of the study. At 
the end of this period, CTC North will require permission from the sponsor before any documents will 
be destroyed or transferred. 
All immunogenicity laboratory documents will be stored in the GLP archive of the University Medical 
Center Hamburg-Eppendorf and Philipps University Marburg for a minimum of 15 years. 
The TMF will be stored in the GLP archive of the University Medical Center Hamburg-Eppendorf for a 
minimum of 30 years. 
If documents shall be retained for a longer period, it is the responsibility of the sponsor to inform CTC 
North when these documents no longer need to be retained. 
In case of any change concerning the archiving modalities CTC North has to inform the sponsor imme-
diately. 
9.7 
Adverse Events 
9.7.1 Definition of Adverse Events, Period of Observation, Recording of Adverse 
Events  
An Adverse Event (AE) is any untoward medical occurrence in a clinical investigation subject adminis-
tered an Investigational Medicinal Product (IMP) and that does not necessarily have a causal relation-
ship with this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, disease or exacerbation of a pre-existing condition temporally 
associated with the use of a medicinal (test) product, whether or not considered related to the medicinal 
product (ICH Guidance E2A 1995). 
All AEs, including those associated with the protocol, are collected from the time after first administration 
of IMP until the defined follow-up period and are to be recorded on the appropriate AE pages in the 
eCRF and in source documents. Where possible, a diagnosis rather than a list of symptoms should be 
recorded. If a diagnosis has not been made then each symptom should be listed individually.  
A solicited AE is a predetermined event occurring within 14 days after application of IMP, which may 
reflect safety concerns related to the investigational product. The solicited AEs for this study include: 
 
Swelling, redness/ erythema, induration, hematoma or pain at site of injection 
 
Fever 
 
Chills 
 
Myalgia (described to the subject as generalized muscle aches) 
 
Arthralgia (described to the subject as generalized joint aches) 
 
Fatigue 
 
Headache 
 
Gastrointestinal symptoms (nausea, vomiting, abdominal pain, loose stool and/or diarrhea) 
 
Malaise 
 
All AEs must be followed to closure (the subject’s health has returned to his/her baseline status or all 
variables have returned to normal), an outcome is reached, stabilization (the investigator does not ex-
pect any further improvement or worsening of the event), or the event is otherwise explained regardless 
of whether the subject is still participating in the study. When appropriate, medical tests and examina-
tions are performed so that resolution of event(s) can be documented. 

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9.7.2 Severity Categorization of AEs 
The severity of AEs must be recorded during the course of the event including the start and stop dates 
for each change in severity. An event that changes in severity should be captured as a new event. 
Worsening of pre-treatment events, after initiation of investigational medicinal product, must be recorded 
as new AEs. 
The medical assessment of severity is determined by using the following definitions: 
Mild: 
A type of AE that is usually transient and may require only minimal treatment or therapeutic 
intervention. The event does not generally interfere with usual activities of daily living. 
Moderate: A type of AE that is usually alleviated with additional specific therapeutic intervention. The 
event interferes with usual activities of daily living, causing discomfort but poses no signif-
icant or permanent risk of harm to the research subject. 
Severe: 
A type of AE that interrupts usual activities of daily living, or significantly affects clinical 
status, or may require intensive therapeutic intervention. 
Additionally, the severity of AEs will be graded according to the toxicity scale described in section 9.7.11. 
If the AE is not defined in the tables of section 9.7.11 the severity will be graded according to NCI CTCAE 
(current version). 
The severity assessment is described more detailed in section 9.7.11. 
9.7.3 Relationship Categorization 
An investigator must make the assessment of relationship to IMP for each AE. The investigator should 
decide whether, in his or her medical judgment, there is a reasonable possibility that the event may have 
been caused by the IMP. If there is no valid reason for suggesting a relationship, then the AE should be 
classified as ‘not related’. Otherwise, if there is any valid reason, even if undetermined or untested, for 
suspecting a possible cause-and-effect relationship between the investigational medicinal product and 
the occurrence of the AE, then the AE should be considered ‘related’. The causality must be documented 
in the source document. 
The following additional guidance may be helpful: 
Term 
Relationship 
Definition 
Related 
Yes 
The temporal relationship between the event and the admin-
istration of the IMP is compelling and/or follows a known or 
suspected response pattern to that product, and the event 
cannot be explained by the subject’s medical condition, other 
therapies, or accident. 
Not Related 
No 
The event can be readily explained by other factors such as 
the subject’s underlying medical condition, concomitant ther-
apy, or accident and no plausible temporal or biologic rela-
tionship exists between the investigational medicinal product 
and the event. 
 
9.7.4 Outcome Categorization 
The outcome of AEs must be recorded during the course of the study in the eCRF. Outcomes are as 
follows: 
 
Recovered/resolved 
 
Recovering/resolving 
 
Not recovered/not resolved/ ongoing 
 
Recovered/ resolved with sequelae 
 
Fatal  
 
Unknown 

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9.7.5 Clinical Laboratory Evaluations 
A change in the value of a safety laboratory investigation can represent an AE if the change is clinically 
relevant or if, during treatment with the investigational medicinal product, a shift of a parameter is ob-
served from a normal value to an abnormal value, or a further worsening of an already abnormal value. 
When evaluating such changes, the extent of deviation from the reference range, the duration until return 
to the reference range, either while continuing treatment or after the end of treatment with the IMP, and 
the range of variation of the respective parameter within its reference range, must be taken into consid-
eration. 
If, at the end of the treatment phase, there are abnormal laboratory values which were not present at 
baseline, further clinical or laboratory investigations should be performed until the values return to within 
reference range or until a plausible explanation (e.g., concomitant disease) is found for the pathological 
laboratory values. 
The Investigator should decide, based on the above criteria and the clinical condition of a subject, 
whether a change in a laboratory parameter is clinically significant and therefore represents an AE. 
9.7.6 Abuse, Misuse, Overdose, and Medication Error  
Abuse, misuse, overdose, or medication error (as defined below) must be reported to the sponsor ac-
cording to the SAE reporting procedure whether or not they result in an AE/SAE.  
Abuse - Persistent or sporadic intentional intake of a study medication at a dose higher than prescribed 
per protocol (but below the dose defined for overdose) or when used for non-medical purpose (e.g. 
altering one’s state of consciousness)  
Misuse - Intentional or unintentional use of a study medication other than as directed or indicated at any 
dose, which is at or below the dose defined for overdose. (Note: this includes a situation where the study 
medication is not used as directed at the dose prescribed by the protocol) 
Overdose - Intentional or unintentional intake of a dose of study medication higher than the protocol 
prescribed dose for each subject. 
Medication Error - A mistake made in prescribing, dispensing, administration, and/or use of the study 
medication. For studies, medication errors are reportable only as defined below. 
Administration of an expired product should be considered as a reportable medication error when asso-
ciated with an AE, or if otherwise appropriate. 
Cases of subjects missing doses of product are not considered reportable as medication errors. 
9.7.7 Serious Adverse Event (SAE) Procedures 
All AEs and SAEs occurring following IMP injection and end of study visit and observed by the Investi-
gator or reported by the subject, respectively, whether or not attributed to study intervention, will be 
recorded in the eCRF. All AEs that result in a subject’s withdrawal from the study will be followed up 
until a satisfactory resolution occurs, or until a non-study related causality is assigned (if the subject 
consents to this). 
Besides the occurrence also the relationship an intensity of these events will be determined. 
9.7.7.1 Reporting Procedures 
All initial SAE reports must be reported by the Investigator to the CTC North Safety Department within 
24 hours of the first awareness of the event. All SAE follow-up reports must be reported in a timely 
manner. The Investigator must complete, sign, and date the Serious Adverse Event Form and verify the 
accuracy of the information recorded on the form with the corresponding source documents (Note: 
source documents are not to be sent unless requested) and fax or e-mail the form to the CTC North 
Safety Department: 
Name:  
 
CTC North Safety 
Fax number: 
 
+49 40 524719 222  
Phone number:  
+49 40 524719 225 
Email:  
 
pharmacovigilance@ctc-north.com  
CTC North forwards all SAEs for review to the medical monitor of the sponsor. He makes SAEs causality 
and expectedness assessment and forwards it to the CTC North Safety Department. In case an SAE is 

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considered related to the study medication (i.e. a SUSAR occurs), the CTC North Safety Department 
informs the medical monitor and coordinating principle investigator (LKP). On behalf of the sponsor CTC 
North has to inform the competent authority and the ethics committee about the SUSAR as soon as 
possible but not later than 15 calendar days. SAE resulting in death, has to be reported as soon as 
possible but not later than 7 calendar days.  
9.7.7.2 Serious Adverse Event Definition 
A Serious Adverse Event (SAE) is any untoward medical occurrence (whether considered to be related 
to investigational medicinal product or not) that at any dose: 
 Results in death 
 Is life-threatening 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Is a congenital abnormality/birth defect 
 Is an Important Medical Event, i.e., an event that may jeopardize the subject and may require 
medical or surgical intervention to prevent one of the outcomes listed in this definition.  
Hospitalizations which are the result of elective or previously scheduled surgery for pre-existing condi-
tions which have not worsened after initiation of treatment should not be classed as SAEs. For example, 
an admission for a previously scheduled ventral hernia repair would not be classed as an SAE. 
However, complication(s) resulting from a hospitalization for an elective or previously scheduled surgery 
that meets serious criteria must be reported as an SAE(s). 
9.7.8 Definition of serious adverse reaction (SAR) 
A serious adverse reaction (SAR) is an AE (expected or unexpected) that is both serious and, in the 
opinion of the reporting Investigator or sponsors, believed to be possibly, probably or definitely due to 
an IMP or any other study treatments, based on the information provided. 
9.7.9 Definition of suspected unexpected serious adverse reaction (SUSAR) 
A suspected unexpected serious adverse reaction (SUSAR) is a SAE that is unexpected and thought 
to be possibly, probably or definitely related to an IMP. No category of SAE has been defined as ‘ex-
pected.’ 
9.7.9.1 SAE Onset and Resolution Dates 
The onset date of the SAE is defined as the date the event meets serious criteria. The resolution date 
is the date the event no longer meets serious criteria, the date the symptoms resolve, or the event is 
considered chronic. In the case of hospitalizations, the hospital admission and discharge dates are con-
sidered the onset and resolution dates, respectively.  
9.7.9.2 Fatal Outcome 
Any SAE that results in the subject’s death (i.e. the SAE was noted as the primary cause of death) 
should have fatal checked as an outcome and the resolution date of death recorded as the resolution 
date. For all other events ongoing at time of death that did not contribute to the subject’s death, the 
outcome should be considered not resolved, without a resolution date recorded. 
For any SAE that results in the subject’s death or any ongoing events at the time of death, the action 
taken with the IMP should be recorded as “dose not changed” or “not applicable” (if the subject never 
received IMP).  
9.7.10 Regulatory Agency, Independent Ethics Committee, and Investigative Site 
Reporting 
The sponsor is responsible for SUSAR reporting to the national regulatory authorities central Independ-
ent Ethics Committees (IECs) and to inform all investigators.  
9.7.11 Assessment of Severity 
The severity of clinical and laboratory AE will be assessed according to the following scales. 

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9.7.11.1 
Toxicity Grading Scale for Local Adverse Events 
Table 3: Toxicity grading scale for local adverse events 
*In addition to grading the measured local reaction at the greatest single diameter, the measurement should be 
recorded as a continuous variable. 
**Induration/swelling should be evaluated and graded using the functional scale as well as the actual measure-
ment. 
From the FDA’s 2007 voluntary guidance: (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceCom-
plianceRegulatoryInformation/Guidances/ Vaccines/ucm091977.pdf) 
9.7.11.2 
Toxicity Grading Scale for Physical Observations 
Table 4: Toxicity grading scale for physical observations 
Observation 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 
5 
Fever (axil-
lary) 
38.0° - 39.0°C 
> 39.0°C - 40.0°C 
> 40.0°C for ≤ 24 
hours 
> 40.0°C for ≥ 24 
hours 
Death 
Tachycardia 
(bpm)* 
Asymptomatic, 
intervention not 
indicated 
Symptomatic, non-ur-
gent medical interven-
tion indicated 
Urgent medical inter-
vention indicated 
Life-threatening con-
sequences, urgent 
intervention indicated 
Death 
Bradycardia 
(bpm)** 
Asymptomatic, 
intervention not 
indicated 
Symptomatic, medical 
intervention indicated 
Severe, medically 
significant, urgent 
medical intervention 
indicated 
Life-threatening con-
sequences, urgent 
intervention indicated 
Death 
Hyperten-
sion** 
 
Prehyperten-
sion 
(systolic 
BP 
120-
139 mmHg 
or 
diastolic BP 80-
89 mmHg) 
 
Stage 1 hypertension 
(systolic 
BP 
140-
159 mmHg or diastolic 
BP 
90-99 mmHg); 
medical intervention in-
dicated; recurrent or 
persistent 
(≥24 h); 
symptomatic increase 
by >20 mmHg (dias-
tolic) 
or 
to 
>140/90 mmHg if pre-
viously within normal 
limits; monotherapy in-
dicated  
Stage 2 hypertension 
(systolic 
BP 
≥160 mmHg or dias-
tolic 
BP 
≥100 mmHg); medi-
cal intervention indi-
cated; more than one 
drug or more inten-
sive 
therapy 
than 
previously used indi-
cated  
Life-threatening con-
sequences (e.g., ma-
lignant hypertension, 
transient or perma-
nent neurologic defi-
cit, hypertensive cri-
sis); urgent interven-
tion indicated  
Death 
Hypotension 
Asymptomatic, 
intervention not 
indicated 
Non-urgent medical in-
tervention indicated 
Medical intervention 
or hospitalization in-
dicated 
Life-threatening and 
urgent 
intervention 
indicated 
 
 
Death 
 
Definitions 
Local Reaction 
Grade 0 
 
Normal 
Grade 1 
 
Mild 
Grade 2 
 
Moderate 
Grade 3 
 
Severe 
Grade 4 
Potentially life-
threatening 
Redness/erythema* 
<25 mm 
25-50 mm 
51-100 mm 
>100 mm 
Necrosis or ex-
foliative derma-
titis 
Swelling/induration** 
<25 mm 
25-50 mm 
and does not 
interfere with 
activity 
>50 mm or inter-
feres with activity 
Prevents daily ac-
tivity 
Necrosis 
Pain  
None 
Does not in-
terfere with 
activity 
Interferes with ac-
tivity 
Prevents daily ac-
tivity 
Emergency 
room visit or 
hospitalization 

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Fever 
A disorder characterized by elevation of the body's temperature above the upper limit of normal. 
Tachycardia 
A disorder characterized by a dysrhythmia with a heart rate greater than 100 beats per minute. 
Bradycardia 
A disorder characterized by a dysrhythmia with a heart rate less than 60 beats per minute. 
Hypertension 
A disorder characterized by a pathological increase in blood pressure; a repeatedly elevation in the 
blood pressure exceeding 140 over 90 mmHg. 
Hypotension 
A disorder characterized by a blood pressure that is below the normal expected for an individual in a 
given environment. 
*Taken after ≥10 minutes at rest; **when resting heart rate is between 60–100 beats per minute. Use clinical 
judgement when characterizing bradycardia among some healthy subjects, for example, conditioned athletes.  
From CTCAE v4 (http://evs.nci.nih.gov/ftp1/CTCAE/CTCAE_4.03_2010-06-14_QuickReference_5x7.pdf) 
9.7.11.3 
Toxicity grading scale for systemic AEs excluding the physical observations 
listed above 
Table 5: Toxicity grading scale for systemic AEs 
From the FDA’s 2007 voluntary guidance: (http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceCom-
plianceRegulatoryInformation/Guidances/ Vaccines/ucm091977.pdf) 
Systemic 
sign/symptom 
Grade 1 
 
Mild 
Grade 2 
 
Moderate 
Grade 3 
 
Severe 
Grade 4 
Potentially life-threat-
ening 
Headache 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation 
and/or hospitalization 
Fatigue 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation or 
hospitalization 
Myalgia 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation 
and/or hospitalization 
Arthralgia 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation 
and/or hospitalization 
Chills 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation 
and/or hospitalization 
Sweats 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation 
and/or hospitalization 
Subjective Fever 
No interference 
with activity 
Some interference 
with activity 
Significant; prevents 
daily activity 
Medical consultation 
and/or hospitalization 
Nausea 
No interference 
with activity 
Some interference 
with activity not requir-
ing medical interven-
tion 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or hospitalization 
Vomiting 
No interference 
with activity 
Some interference 
with activity not requir-
ing medical interven-
tion 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or hospitalization 
Abdominal Pain 
No interference 
with activity 
Some interference 
with activity not requir-
ing medical interven-
tion 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or hospitalization 
Diarrhea 
No interference 
with activity 
Some interference 
with activity not requir-
ing medical interven-
tion 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or hospitalization 
Other systemic 
symptoms 
No interference 
with activity 
Some interference 
with activity  
Prevents daily activity 
Medical consultation 
and/or hospitalization 

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9.8 
Statistical Methods Planned in the Protocol and Determination of Sample Size 
9.8.1 Statistical and Analytical Plan 
Details for the statistical evaluation of the results will be given in a separate statistical analysis plan 
(SAP). 
9.8.1.1 Software to be used 
All statistical calculations will be carried out using SAS language and procedures (SAS 9.2 or higher 
version SAS-Institute, Cary NC, USA). 
9.8.1.2 Eligibility for Statistical Evaluation 
Eligibility of subjects will be determined within the data review meeting (DRM). The following patient 
populations will be investigated: 
 
Safety population: All subjects receiving at least once the study medication will be included into 
the safety evaluation (safety collective). 
 
Per protocol population: All subjects who have received both injections and who have not with-
drawn within the first 7 days after the second injection will be included for the per protocol anal-
ysis. 
All safety endpoints will be investigated in the safety population. As a sensitivity analyses, the analysis 
of the safety endpoints will be repeated in the per protocol population. All other endpoints will be inves-
tigated in the per protocol population only. 
9.8.1.3 Statistical analyses 
For metric variables, the arithmetic mean (Mean), the standard deviation (SD), coefficient of variation 
(CV), absolute minimum (Min) and maximum (Max) and median (Med) will be reported per dose level. 
For parameters that appear to be log-normally distributed, the geometric mean (GeoM) and the coeffi-
cient of variation (CV) may be reported.  
Laboratory values and their change from baseline will be summarized and displayed graphically by dose 
level. Values outside of the reference range will be flagged and tabulated. Unless otherwise specified, 
baseline is defined as the time-point closest to but prior to the first administration of the vaccine. 
Categorical variables will be summarized by dose level in frequency tables (number and percentages). 
The individual subject values will be listed.  
It is not planned to test any hypotheses in a confirmatory sense. If deemed necessary, 95% confidence 
intervals will be provided for means (metric variables) and percentages (categorical variables). 
Interim analyses may be performed upon request of the sponsor. 
9.8.2 Determination of Sample Size 
For this FIH study no formal criteria are available in order to fix the sample size. The MVA vaccine is 
licensed and has been tested in various clinical trials as listed in table 15 of the IB [13]. 24 subjects (10 
subjects on dose level 107 pfu, 10 subjects on dose level 108 pfu and 4 subjects on placebo) were 
enrolled in a dose escalation study of MVA-BN [16]. In a phase I/IIa study of MVA-H5-sfMR with 80 
subjects, 20 subjects received a dose of 107 pfu (10 subjects in one immunization, 10 subjects in two 
immunizations) and 20 subjects received a dose of 108 pfu (10 subjects in one immunization, 10 subjects 
in two immunizations) [17]. Therefore, N=24 subjects (12 subjects per dose level) are considered suffi-
cient to identify major safety risk and to prove the concept. 
9.9 
Changes in the conduct of the study or planned analysis 
Modifications of the protocol are permitted only if they are authorized by the sponsor and the investigator 
in writing.  
Deviations and changes to the study protocol will be classified by the sponsor and the study center as: 
Note-to-File: This refers to clarifications which are not considered changes of the protocol. 
Study protocol amendment: This refers to changes of the protocol. If they fulfill the criteria as set out in 
according to §10 (1) GCP-V they need to be approved by the IEC or the competent authority or both of 

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it. Changes to the study protocol may also induce revision of the subject information sheet/informed 
consent form. Accordingly, subjects undergoing trial assessment procedures at the time of implementa-
tion of the change have to be given the amended version and have to be asked for consent to continue 
on this amended trial.  
9.10 
Local Safety Board 
During the trial, the Local Safety Board will review and judge the safety, tolerability, after each dose-
step and prior to the next dose-step of the trial. Based on these data the Local Safety Board will/may 
decide  
 Whether there will be a next dose cohort and if the planned dose for the next dose cohort has 
to be reduced.  
 Whether there will be added additional dose step(s) or dose step(s) will be repeated. 
Evaluation will take the results of the pre-clinical studies and the ongoing phase I studies in prior men-
tioned other countries into account. 
An interim safety report, summarizing the safety (AEs, vital signs, 12-lead ECGs, and laboratory safety 
data) will be prepared and reviewed by the Principal Investigator and Medical Monitor before the second 
immunization for each dose cohort. 
Planned dose escalation will occur after the second immunization of all subjects of the 1st dose group 
following a review of the interim safety report summarizing the safety (AEs, vital signs, 12-lead ECGs, 
and laboratory safety data) and any available immunological data by the Principal Investigator and Med-
ical Monitor. 
The dose for the next escalation step may be reduced if there are concerns about the safety. A dose 
level may be repeated and furthermore, additional dose step(s) may be added but not exceeding dose 
of 1x108 pfu MVA-MERS. The decision to repeat and/or to modify the dose level and/or to add additional 
dose steps will be taken by the Local Safety Board.  
In addition, a Local Safety Board meeting will be conducted whenever safety relevant data occur that 
might have an influence on the trial.  
Members of the Local Safety Board will be the medical monitor, as well as the Principal Investigator, or 
at least one of the deputies and a representative of the sponsor.  
At a minimum the holding rules (criteria for termination of the study) specified in the protocol will auto-
matically apply (if activated) for not proceeding with a higher dose.  
The decisions of the Local Safety Board meeting will be briefly summarized by CTC North and signed 
by all members involved in the meeting and the decision. The summarized safety report of each Local 
Safety Board Meeting will be submitted to the competent national authority (Paul-Ehrlich-Institute) and 
the independent ethics committee (Ethik-Kommission der Ärztekammer Hamburg) for notification. 
10 
REPORTS 
All reports to the sponsor will be in English. The sponsor will receive the original final report. A copy of 
the report will be archived at the archives contracted by the study center. 
The final report is the property of the sponsor. Publication of the report or of part of it may only be allowed 
when authorized by the sponsor in consultation with the study center. 
10.1 Final Report 
All clinical, analytical and statistical results will be presented in a final report. The outline of this report 
will accord to the EFPIA/CPMP document "Structure and Content of Clinical Study Reports" of July 17, 
1996. 
The sponsor will receive an electronic copy of the eCRF for archival. 
 

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10.2 Additional reports 
Upon completion of the study, a short report will be sent to the ethics committee, stating any undesired 
event and indicating whether study objectives have been attained. Short reports to the authorities after 
study termination will be provided as required by law 

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11 
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