A Phase II/III Randomized, Double-blind Controlled Study to Compare the Safety and Immunogenicity of 1 or 2 Doses of Acellular Pertussis Vaccines Containing Genetically-detoxified Pertussis Toxin in Young Adults Previously Primed With Acellular Pertussis Vaccines
Phase: PHASE2
Conditions: Pertussis, Vaccine-Preventable Diseases
Sponsor: University Hospital, Geneva

 
PHASE II/III Pertagen2x VACCINE TRIAL: PROTOCOL v1.2 
 
Version 1.2, 23.07.2021 
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A Phase II/III randomized, double-blind controlled study to compare the safety and 
immunogenicity of 1 or 2 doses of acellular pertussis vaccines containing 
genetically-detoxified pertussis toxin in young adults previously primed with 
acellular pertussis vaccines. 
Short title: Pertagen2x  
 
 
Sponsor   
 
Geneva University Hospitals 
4 Rue Gabrielle Perret-Gentil 
1205 Geneva, Switzerland 
 
Principal 
Investigator   
Dr. Géraldine Blanchard-Rohner, MD, PhD 
Immunology and Vaccinology Division  
Department of Pediatrics 
University Hospitals of Geneva (HUG) 
Rue Willy-Donzé 6 
1211 Genève 14 
Phone +41 79 553 4482 
Email: Geraldine.blanchardrohner@hcuge.ch 
 
 
Funding 
source 
Request for funding has been submitted.  
Center for Vaccinology  
Medical Faculty (UNIGE) and University Hospitals of Geneva (HUG) 
CMU, 1 Michel-Servet 
1211 Geneva 4 
 
 
CONFIDENTIALITY STATEMENT 
The information contained in this document is the property of HUG. 
Do not copy or distribute to others without written permission from the Sponsor and BioNet Asia. 
It is provided to you in confidence as a potential reviewer or investigator. 
 
 
 

 
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GENERAL INFORMATION/ STUDY ADMINISTRATIVE STRUCTURE 
Study type 
Phase II/III clinical trial  
Study categorization 
C 
Study product 
Pertagen® (BioNet-Asia acellular pertussis vaccine) 
Sponsor  
 
 
 
Geneva University Hospitals 
Center for Vaccinology 
4 Rue Gabrielle Perret-Gentil 
1205 Geneva, Switzerland 
Vaccine manufacturers 
BioNet-Asia Co., Ltd. (BNA) 
19 Soi Udom Suk 37,  
Sukhumvit 103 Rd.,  
Prakanong, Bangkok,  
10260 Thailand 
Sanofi Aventis (Suisse) SA  
Route de Montfleury 3 
1214 Vernier/Geneva 
Switzerland 
 
 
 
Qualified Person 
Dario Franscesco Creschi 
Principal Investigator 
Dr. Géraldine Blanchard-Rohner, MD, PhD 
Vaccinology and Immunology Division 
Department of Pediatrics 
University Hospitals of Geneva (HUG) 
Rue Willy-Donzé 6 
1211 Genève 14 
Phone +41 79 553 4482 
Email: Geraldine.blanchardrohner@hcuge.ch 
Trial site 
Plateforme de Recherche Clinique de Pédiatrie, Gynécologie et Obstétrique (HUG) 
Local laboratories 
University Hospitals of Geneva 
Rue Gabrielle-Perret-Gentil 4 
Geneva, Switzerland 1205 
Immunology laboratories 
Vaccinology Laboratory, HUG 
Center for Vaccinology, University of Geneva 
Biology Laboratory of BioNet-Asia Co., Ltd. 
Clinical investigators 
Dr. Géraldine Blanchard-Rohner, MD, PhD 
Dr. Natasha Loevy 
Immunologic evaluator 
Prof. Claire-Anne Siegrist, MD 
External collaborators 
Collaborating immunology research laboratories 
 
External monitor 
Center for Clinical Research (HUG) 
Current protocol version 
1.2 

 
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Version history 
 
Date 
Version 
Changes 
By 
24.09.2020 
1.0 
Initial draft 
G. Blanchard 
Rohner 
11.05.2021 
1.0 
Final version v1.0 
G.Blanchard 
Rohner 
01.07.2021 
1.1 
Revised version following CCER review 
G.Blanchard 
Rohner 
23.07.2021 
1.2 
Revised version following CCER review 
G. Blanchard 
Rohner  
 
 
 
 
 
 
 

 
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SIGNATURE PAGE 
Declaration of Sponsor 
 
Title: A Phase II/III randomized, double-blind controlled study to compare the safety and 
immunogenicity of 1 or 2 doses of acellular pertussis vaccines containing genetically-detoxified 
pertussis toxin in adults previously primed with acellular pertussis vaccines. 
 
This study protocol was subjected to critical review. The information it contains is consistent with 
current knowledge of the risks and benefits of the investigational product, as well as with the moral, 
ethical, and scientific principles governing clinical research as set out in the Declaration of Helsinki, 
[2013] (APPENDIX 1) and the guidelines on Good Clinical Practice. 
 
 
 
 
 
 
 
 
 
Dr. Géraldine Blanchard Rohner  
      
             _________ 
Sponsor representative 
Signature 
Date     
 
 
 
Declaration of Principal Investigator 
 
I, the undersigned, have reviewed the protocol entitled “A Phase II/III randomized, double-blind 
controlled study to compare the safety and immunogenicity of 1 or 2 doses of acellular pertussis 
vaccines containing genetically-detoxified pertussis toxin in adults previously primed with acellular 
pertussis vaccines,” version 1.2, dated 23.07.2021, including appendices. I will conduct the clinical 
study as described and I will adhere to Good Clinical Practices/International Conference on 
Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use 
(GCP/ICH)and all ethical and regulatory considerations stated under the Federal Law on Medicinal 
Products and Medical Devices (TPA/LPTh, 15 December 2000), Federal Law on Human Subjects 
Research (HRA/LRH, 30 September 2011) and the Ordinance on Clinical Trials in Human Research 
(ClinO/OClin, 20 September 2013). 
 
 
 
 
Dr. Géraldine Blanchard Rohner         
       
 
_________ 
Principal Investigator 
Signature 
Date 
 
 
 
 

 
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TABLE OF CONTENTS 
CONFIDENTIALITY STATEMENT ......................................................................................... 1 
GENERAL INFORMATION/ STUDY ADMINISTRATIVE STRUCTURE ....................................... 2 
SIGNATURE PAGE.............................................................................................................. 4 
PROTOCOL SYNOPSIS ........................................................................................................ 8 
STUDY FLOW CHART ....................................................................................................... 15 
ABBREVIATIONS AND DEFINITIONS ................................................................................. 16 
1 BACKGROUND AND RATIONALE ................................................................................... 17 
1.1 The recurrence of pertussis and need for optimized pertussis vaccines ............................... 17 
1.2 Clinical evidence to date: development of aP vaccines including genetically-detoxified PT .. 17 
1.3 Rationale for the current study and proposed vaccine schedule ......................................... 20 
2 OBJECTIVES AND ENDPOINTS ....................................................................................... 21 
2.1 Primary objective .............................................................................................................. 21 
2.1.1 Primary outcome measures ......................................................................................... 21 
2.2 Secondary objectives ......................................................................................................... 22 
2.2.1 Safety outcome .......................................................................................................... 22 
2.2.2 Main secondary immunogenicity outcomes ................................................................. 22 
2.3 Exploratory Outcomes Measures ....................................................................................... 22 
3 CLINICAL STUDY MATERIALS ......................................................................................... 23 
3.1 Study vaccines .................................................................................................................. 23 
3.2 Packaging, Labeling, and Storage of Vaccines ..................................................................... 23 
3.3 Preparation and Administration ........................................................................................ 24 
3.4 Clinical Study Supply, Dispensing, and Accountability ......................................................... 24 
4 STUDY DESIGN ............................................................................................................. 24 
4.1 Overall Study Design ......................................................................................................... 24 
4.2 Study population and entry criteria ................................................................................... 25 
4.2.1 Informed consent ........................................................................................................ 25 
4.2.2 Inclusion and exclusion criteria.................................................................................... 25 
4.2.3 Compliance with dosing regimen................................................................................. 27 
4.3 Randomization .................................................................................................................. 27 
4.4 Formal safety analyses ...................................................................................................... 27 
5 CONDUCT OF STUDY .................................................................................................... 29 
5.1 Study visits ....................................................................................................................... 29 
5.1.1Visit 1: Randomization, assessment and immunization, Day 0 ....................................... 29 
5.1.2Phone contact (Day 7 +/-1) .......................................................................................... 30 
5.1.3Visit 2 (Day 28 +7) ........................................................................................................ 30 
5.1.4Visit 3 (Day 180 +/- 30) ................................................................................................ 30 
5.1.5Phone contact (Day 187 +/-1) ....................................................................................... 31 
5.1.6Visit 4 (Day 210 +7) ...................................................................................................... 31 
5.1.7Visit 5 (Day 365 +/- 30) ................................................................................................ 31 
5.2 Unscheduled visits ............................................................................................................ 31 
5.3 Study assessments ............................................................................................................ 32 
5.3.1 Safety tests ................................................................................................................. 32 
5.3.2 Immunogenicity tests.................................................................................................. 32 
6 STUDY DISCONTINUATION ........................................................................................... 32 

 
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6.1 Study termination ............................................................................................................. 32 
6.2 Study withdrawal .............................................................................................................. 32 
6.3 Procedures for handling subjects with premature study discontinuation ............................ 33 
6.4 Breaking the randomization code ...................................................................................... 34 
7 SAFETY ASSESSMENT ................................................................................................... 34 
7.1 Adverse events ................................................................................................................. 34 
7.2 Adverse reactions ............................................................................................................. 34 
7.3 Serious adverse events ...................................................................................................... 35 
7.4 Serious adverse drug reaction (SADR) ................................................................................ 35 
7.5 Suspected unexpected serious adverse reaction (SUSAR) ................................................... 35 
7.6 Causality assessment......................................................................................................... 35 
7.7 Reporting procedures for all adverse events ...................................................................... 36 
7.7.1 Reporting procedures for SAE ...................................................................................... 36 
7.7.2 Reporting procedures for SUSAR ................................................................................. 36 
7.8 Assessment of severity ...................................................................................................... 37 
7.9 Summary of risk mitigation strategies ................................................................................ 40 
8 STATISTICAL ANALYSIS ................................................................................................. 40 
8.1 Sample size calculation ...................................................................................................... 40 
8.2 Safety analysis .................................................................................................................. 40 
8.3 Immunogenicity analyses .................................................................................................. 40 
9 QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES ....................................... 41 
9.1 Investigator procedures .................................................................................................... 41 
9.2 Monitoring........................................................................................................................ 41 
9.3 Modification to protocol ................................................................................................... 41 
9.4 Protocol and GCP deviation ............................................................................................... 41 
9.5 Trial progress .................................................................................................................... 41 
9.6 Publication policy .............................................................................................................. 41 
10 ETHICAL AND REGULATORY ASPECTS .......................................................................... 42 
10.1 Declaration of Helsinki .................................................................................................... 42 
10.2 ICH Guidelines for Good Clinical Practice (GCP) ................................................................ 42 
10.3 Study registration ............................................................................................................ 42 
10.4 Categorization of study ................................................................................................... 42 
10.5 Ethics committee and regulatory agency review ............................................................... 42 
10.6 Declaration of interest ..................................................................................................... 42 
10.7 Informed consent ............................................................................................................ 42 
10.8 Benefits and risks to the participant................................................................................. 42 
10.9 Subject confidentiality ..................................................................................................... 42 
11 DATA HANDLING AND RECORD KEEPING .................................................................... 44 
11.1 Data handling and management ...................................................................................... 44 
11.2 Record keeping ............................................................................................................... 44 
11.3 Source data and case report forms (CRFs) ........................................................................ 44 
11.4 Data protection and ownership ....................................................................................... 45 
11.5 Retention and destruction of study data and biological material ...................................... 45 
12 FINANCING AND INSURANCE ...................................................................................... 46 
12.1 Financing ........................................................................................................................ 46 
12.2 Insurance ........................................................................................................................ 46 
12.3 Compensation of subjects ................................................................................................ 46 
REFERENCES ................................................................................................................... 47 

 
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List of Tables  
Table 1. Study groups ............................................................................................................................ 11 
Table 2. Composition of each dose of 0.5mL presented in pre-filled syringe ...................................... 11 
Table 3. Schedule of Assessment .......................................................................................................... 15 
Table 4. Anti-PT and anti-FHA antibodies by study groups................................................................... 20 
Table 5. Toxicity grading scale for local adverse events ....................................................................... 37 
Table 6. Toxicity grading scale for Vital signs ........................................................................................ 38 
Table 7. Toxicity grading scale for systemic AEs excluding the vital signs listed above........................ 39 
Table 8. Risk mitigation strategies ........................................................................................................ 40 
 
List of Figures 
Figure 1. Study Flow Chart .................................................................................................................... 15 
Figure 2. Binding (left) or neutralizing (right) anti-PT IgG antibodies before and after immunization 
with BNA aPor Tdap vaccines or Adacel® .............................................................................................. 19 
Figure 3. Antibody responses to recombinant acellular pertussis vaccine (r-aP Pertagen®) compared 
to the standard vaccine containing chemically detoxified pertussis toxin (cd/Tdap Boostrix®) .......... 21 
Figure 4. Memory B-cell response to recombinant acellullar pertussis vaccine (r-aP Pertagen®) 
compared to the standard vaccine containing chemically detoxified pertussis toxin (cd/Tdap 
Boostrix®) .............................................................................................................................................. 21 
Figure 5. Workflow for reporting of serious adverse events and SUSAR.............................................. 37 
 
 

 
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PROTOCOL SYNOPSIS 
PROTOCOL SYNOPSIS – PHASE II/III 2 doses rPT-VACCINE TRIAL 
PROTOCOL TITLE: 
A Phase II/III randomized, double-blind controlled study to compare the safety 
and immunogenicity of 1 or 2 doses of acellular pertussis vaccines containing 
genetically-detoxified pertussis toxin in adults previously primed with acellular 
pertussis vaccines. 
PRINCIPAL 
INVESTIGATOR:  
Dr Géraldine Blanchard Rohner, MD, PhD 
STUDY CENTER: 
University Hospitals of Geneva, Clinical Trials Unit, Geneva, Switzerland 1205 
SPONSORING 
INSTITUTION: 
 
Geneva University Hospitals  
4 Rue Gabrielle Perret-Gentil 
1205 Geneva, Switzerland 
MANUFACTURERS: 
BioNet-Asia Co., Ltd. (BNA)   
19 Soi Udom Suk 37,  
Sukhumvit 103 Rd.,  
Prakanong, Bangkok,  
10260 Thailand 
Sanofi Aventis (Suisse) SA  
 
 
 
1214 Vernier/Geneva 
Switzerland 
Qualified person: 
Dario Franscesco Cresci 
CLINICAL 
INVESTIGATORS: 
Dr. Géraldine Blanchard-Rohner, MD, PhD 
Dr. Natasha Loevy 
IMMUNOLOGICAL 
EVALUATOR: 
Prof. Claire-Anne Siegrist, MD 
EXTERNAL 
COLLABORATORS: 
Collaborating immunology research laboratories 
EXTERNAL MONITOR: 
Center for Clinical Research (HUG) 
NAME OF 
INVESTIGATIONAL 
PRODUCT: 
Pertagen® (BioNet-Asia acellular pertussis vaccine) 
NAME OF ACTIVE 
INGREDIENTS: 
Genetically detoxified pertussis toxin (rPT) and filamentous hemagglutinin (FHA), 
alum adsorbed 
INVESTIGATIONAL 
PRODUCT DOSAGE, 
SCHEDULE, AND MODE 
OF ADMINISTRATION: 
Product dosage: 
Group 1:  
Pertagen® (BioNet-Asia): recombinant Pertussis Toxin (rPT) 
 
Revaxis® (Sanofi Aventis): tetanus toxoid, 20 UI; diphtheria toxoid 2 UI; 
inactivated polio viruses. 
Group 2: Pertagen®  
Schedule: 
One vaccination on Day 0 and 6 months later for each volunteer. 
Group 1 will receive one dose of Revaxis® followed by 1 dose of Pertagen®. 
Group 2 will receive two doses of Pertagen®. 
A dose of Revaxis® will be offered at the last visit if useful for protection.  
Mode of Administration: 
Intramuscular injection into the deltoid region of the upper extremity, using a 
syringe with a 1 to 1.5 inch #25-gauge sterile needle.  
 
 
 
 
 

 
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PROTOCOL SYNOPSIS – PHASE II/III 2 doses rPT-VACCINE TRIAL 
TRIAL DESIGN: 
Phase II/III, randomized, double-blind controlled trial  
STUDY POPULATION: 
Adults aged 18-30 years previously primed with acellular pertussis vaccines (see 
entry criteria below).  
SAMPLE SIZE: 
100 volunteers 
FOLLOW-UP PERIOD: 
6 months following the second injection  
STUDY PERIOD: 
July 2021 – September 2023 
RATIONALE: 
A significant increase of pertussis incidence is reported in a growing number of 
countries. This resurgence is considered as resulting from the limited durability of 
aP-vaccine-induced immunity and is associated with increased mortality in young 
infants and morbidity at all age groups. As the pertussis immunity acquired through 
immunization or infection is short-lived, its maintenance or reactivation requires 
repeat boosting at regular time points. Thus, novel strategies capable of 
reactivating pertussis immunity are needed.  
The efficacy of current acellular pertussis vaccines (which contain chemically-
detoxified pertussis toxoid (PT)) rapidly wanes, in part because priming and repeat 
immunization with acellular vaccines induce antibodies specific for the chemically-
detoxified PT but unable to efficiently recognize the native PT expressed by B. 
pertussis. 
Clinical studies have shown the superior immunogenicity profile of acellular 
pertussis vaccines including genetically-detoxified PT (rPT) in adults and 
adolescents previously primed with aP. In particular, we showed in a past Geneva 
study in teenagers previously primed with aP that rPT/FHA induced a stronger 
recall response than the current aP-vaccine at one month post-vaccination. 
However, the difference was less clear one year after vaccination, suggesting that 
2 doses may be needed for more sustained immunity. 
In the present study, we would like to assess whether giving two doses of rPT/FHA 
at 6 months interval induces stronger immune responses than a single dose. 
PRIMARY OBJECTIVE: 
To assess B cell responses to two doses compared to one dose of an acellular 
pertussis vaccine (Pertagen®) including genetically detoxified pertussis toxin (rPT) 
when delivered by the intramuscular route to adult volunteers previously primed 
and boosted with chemically-detoxified PT. 
 
The primary endpoint will be the geometric mean concentration (GMC) of anti-
PT neutralizing antibodies assessed 4 weeks (early immunity) and 6 months 
(sustained immunity) following one or two injections of Pertagen® given at 6 
months interval. 
SECONDARY  
OBJECTIVES: 
 
 
 
 
 
 
 
 
 
 
 
To assess the safety of two doses at 6 months interval of intramuscular 
immunization with Pertagen® administered to adults as compared to one dose 
of Pertagen®. 
 
To assess the humoral responses elicited by two doses of Pertagen® as 
compared to a single dose. The following parameters will be assessed at Day 0, 
Day 28 and Month 6 post first and second vaccination: 
o 
Geometric mean concentrations (GMCs) of PT, FHA, tetanus and 
diphtheria-toxoid specific IgG antibodies measured by ELISA 
o 
Seroresponse rates of PT, FHA, tetanus and diphtheria-toxoid specific 
IgG antibodies measured by ELISA 
o 
Seroresponse rates of PT, FHA, tetanus and diphtheria-toxoid specific 
neutralizing antibodies. 

 
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PROTOCOL SYNOPSIS – PHASE II/III 2 doses rPT-VACCINE TRIAL 
EXPLORATORY 
OBJECTIVES: 
 
To assess antibody titers to specific neutralizing and non-neutralizing epitopes 
of PT, by competitive ELISA, following one or two doses of Pertagen®  
 
To compare antibody avidity following one or two doses of Pertagen®  
 
To assess the frequency and phenotype of PT-specific memory B cell responses 
following one or two doses of Pertagen®  
STUDY POPULATION: 
Volunteers, 18-30 years of age 
NUMBER OF SUBJECTS: 
100 (50 subjects per each vaccine group) 

 
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PROCEDURE AND 
FOLLOW-UP: 
This is a phase II/III, single center, randomized, double-blind controlled vaccine 
trial in 18 to 30 years old volunteers. It will be performed at the Plateforme de 
Recherche Clinique de Pédiatrie, Gynécologie et Obstétrique (PGO) of the HUG.  
Volunteers who have signed the informed consent and who gave their written 
assent will be screened clinically for general health status and those who fulfill all 
exclusion and inclusion criteria will be enrolled into the study.  
 
At Day 0, eligible volunteers will undergo a venous bleed for the determination of 
baseline values and enter the randomization scheme, being allocated to one of 
two groups: A (Revaxis® + Pertagen®), B (Pertagen® + Pertagen®) (Tables 1 and 
2). 
 
Group A 
Revaxis® + Pertagen® 
50 subjects 
Group B 
Pertagen® + Pertagen® 
50 subjects 
Table 1. Study groups 
 
 
Pertagen® 
Revaxis® 
Active substance 
Tetanus Toxoid (TT) 
- 
NLT 20IU 
Diphtheria Toxoid (DT) 
- 
NLT 2.0 IU 
Pertussis Toxoid (PT) 
5 µga 
- 
Filamentous Hemagglutinin (FHA) 
5 µg 
- 
Pertactin (PRN) 
- 
- 
Fimbriae type 2/3 
- 
- 
Inactivated polio viruses type 1-2-3  
- 
40U (type 1), 
8U (type 2), 
32U (type 3) 
Adjuvants 
Aluminum Hydroxide  
0.3 mg/dose 
0.35mg/dose 
Volume for Injection 
q.s. to 0.5 mL 
q.s. to 0.5 mL 
a: Recombinant Pertussis Toxin (rPT) 
Table 2. Composition of each dose of 0.5mL presented in pre-filled syringe 
 
Visit 1: Randomized participants will receive one dose of Revaxis® (Group A) or 
one dose of Pertagen® (Group B) by intramuscular injection in the deltoid. All 
volunteers will be observed at the Plateforme de Recherche Clinique PGO for 
30 minutes after immunization.  
 
Diary cards will be distributed to study volunteers to record post-immunization 
local and systemic reactions avec adverse events. Volunteers will complete daily 
diaries for 7 days after immunization.  
 
All volunteers will be followed for 28 days after immunization and all adverse 
events will be collected and monitored for 28 days after vaccination. 
 
Visit 2: At Day 28, a second visit will take place for safety evaluation, blood draw 
and revision of diary cards. Investigators will reconcile and transcribe the Diary 
Card information in the CRF. 
 

 
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Visit 3: At 6 months, a third visit will take place for the second vaccination. 
Randomized participants will all receive one dose of Pertagen® (Groups A and B) 
by intramuscular injection in the deltoid. All volunteers will be observed at the 
Plateforme de Recherche Clinique PGO for 30 minutes after immunization.  
 
Diary Cards will be distributed to study volunteers to record post-immunization 
local and systemic reactions and adverse events. Volunteers will complete daily 
diaries for 7 days after immunization.  
 
All volunteers will be followed for 28 days after immunization and all adverse 
events will be collected and monitored for 28 days after vaccination. 
 
Visit 4: At Day 28 post second immunization, a 4th visit will take place for safety 
evaluation, blood draw, and revision of diary cards. Investigators will reconcile and 
transcribe the Diary Card information in the CRF. 
 
Visit 5: A final visit will take place at 6 months post-second immunization (blood 
draw).  
At this visit, Group 2 participants will be offered one dose of Revaxis® if needed for 
their protection (last dose of tetanus-containing vaccine >= 10 years). 
 
Blood draws performed on Day 0 (Baseline), Day 28, and Month 6 following each 
vaccination will be used to evaluate early and sustained vaccine responses. 
 
The primary statistical analysis will be based upon visit 4 and visit 5 data to 
compare the early and sustained immunogenicity of one or two doses of 
Pertagen®. 

 
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PROTOCOL SYNOPSIS – PHASE II/III 2 doses rPT-VACCINE TRIAL 
SUBJECT INCLUSION 
CRITERIA: 
 
 
 
 
 
 
 
 
 
 
 
 
SUBJECT EXCLUSION 
CRITERIA: 
 
 
Has provided written informed consent; 
 
Male or female, ages 18 to 30 years (inclusive) at the time of enrollment; 
 
With documented history of acellular pertussis immunization (5 doses); 
 
Free of clinically significant health problems, as determined by pertinent 
medical history and clinical examination at study screening; 
 
Non-pregnant, non-lactating females : 
o 
A negative urinary pregnancy test at enrollment; 
o 
If sexually active, female subjects must be willing to use reliable birth 
control measures for 1 month after each vaccination; 
 
Able to attend all scheduled visits during one year and to understand and 
comply with the study procedures; 
 
 
Prior dTpa immunization within the last 5 years or prior dT immunization 
within the last 2 years, or any other investigational vaccine likely to impact on 
interpretation of the trial data; 
 
Suspected or confirmed pertussis infection within the last 10 years or 
documented pertussis infection in a household member within the last 
10 years; 
 
History of severe local or systemic reactions to any vaccination; 
 
Known hypersensitivity or allergy to diphtheria, tetanus, or pertussis-
containing vaccines (including excipients); 
 
Receipt of investigational product up to 30 days prior to enrollment or ongoing 
participation in another interventional clinical trial; 
 
Receipt of licensed vaccines within 30 days of planned study immunization or 
ongoing participation in another clinical interventional trial likely to interfere 
with study results; 
 
Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, 
cardiovascular, or hepatic or renal functional abnormality as determined by 
the Investigator based on medical history and physical exam;  
 
Any confirmed or suspected immunosuppressive or immunodeficient 
condition, including human immunodeficiency virus (HIV) infection, asplenia, 
cytotoxic therapy in the previous 5 years, and/or diabetes; 
 
Has a known history of vaccine-induced Guillain-Barré Syndrome; 
 
Has an active malignancy or recent (<10 years) history of metastatic or 
hematologic malignancy; 
 
Suspected or known alcohol and/or illicit drug abuse within the past 5 years; 
 
Pregnant or lactating female, or female intending to becoming pregnant 
during the study period; 
 
Administration of immunoglobulins within the 120 days preceding study entry 
or planned administration during the study period; 
 
History of blood donation (at least 450 ml) within 30 days of enrollment or 
plans to donate within the 30 days following and preceding each blood draw; 
 

 
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PROTOCOL SYNOPSIS – PHASE II/III 2 doses rPT-VACCINE TRIAL 
SUBJECT EXCLUSION 
CRITERIA (cont): 
 
 
Receipt 
of 
chronic 
(>14 days) 
immunosuppressants 
or 
other 
immune-modifying drugs within 6 months of study entry: 
o 
For corticosteroids, this will mean prednisone or equivalent 
≥0.5 mg/kg/day, 
o 
Intranasal and topical steroids are allowed; 
 
Any other significant finding that, in the opinion of the investigator, would 
increase the risk of the individual’s having an adverse outcome by participating 
in this study. 
SUBJECT TEMPORARY 
EXCLUSION CRITERIA: 
 
 
Acute disease at the time of randomization. (Acute disease in the context of 
this trial is defined as the presence of a moderate or severe illness with or 
without fever.) The vaccine can be administered to persons with a minor 
illness such as mild upper respiratory tract infection with or without low-grade 
febrile illness, i.e. temperature of ≤37.5°C.; 
 
Body temperature documented ≥38°C within 3 days of the intended 
vaccination; 
 
Any other significant finding that, in the opinion of the investigator, would 
temporarily increase the risk of the individual’s having an adverse outcome by 
participating in this study. 
ENDPOINTS 
 
SAFETY: 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMMUNOGENICITY: 
The nature, frequency, and severity of AEs and/or SAEs associated with 
immunization: 
 
Solicited AEs occurring from the time of immunization through 7 days 
following the procedure, facilitated with the use of a diary card. Solicited 
local reactogenicity adverse events include pain, erythema, swelling and 
pruritus at the treatment site. Solicited systemic reactogenicity AE include 
objective fever, subjective fever, chills, myalgia, arthralgia, sudation, 
fatigue, headache, nausea, vomiting and loss of appetite; 
 
Unsolicited AEs from the time of immunization through 28 days following 
immunization; 
 
SAEs from the time of the first treatment through the final study visit. 
 
 
Development and characteristics of PT-and FHA specific antibody and cellular 
responses on Day 0 and Day 28 and Month 6 following first and second 
immunization. 
 
STATISTICAL ANALYSIS: 
The sample size calculation is based on the previous study using the rPT vaccin in 
teenagers in Geneva (Blanchard Rohner et al. CID 2019). In order to have a power 
of 90%, to expect to see a double increase in the neutralising PT antibodies 
following two doses of rPT in comparison to a single dose, we would need 2x35 
volunteers.  
 
Safety analysis will be descriptive. Recorded solicited and unsolicited adverse 
events will be described by treatment group. 
Immunogenicity endpoints and confidence bounds will be calculated for each 
group and compared (using Chi-square or Fisher’s exact test for binary endpoints, 
and Wilcoxon-Mann-Whitney’s test or Kruskal-Wallis test for quantitative 
endpoints). All tests will be two-sided. 
 
STUDY PERIOD: 
One year for each volunteer 
 

 
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STUDY FLOW CHART 
 
Figure 1. Study Flow Chart 
 
Visits 
V1 
 
V2 
V3 
 
V4 
V5 
Enrollment Phone call 
 
 
Phone call 
 
 
Timeline (days) 
0 
7 
28 
180 
187 
210 
365 
Window period 
(days/months) 
  
±1d 
+7d 
±30d 
±1d 
+7d 
±30d 
Informed consent 
X 
 
  
 
 
 
 
Demographics, Medical 
history, Immunization history 
X 
 
 
 
 
 
 
Exclusion/Inclusion 
X 
 
 
 
 
 
 
Physical examination 
X 
 
(X) 
X 
 
(X) 
(X) 
Enrollment 
X 
 
 
 
 
 
 
Randomization 
X 
 
  
 
 
 
 
Blood sampling 
X 
 
X 
X 
 
X 
X 
Immunization 
(Pertagen®/Revaxis®) 
X 
 
  
X 
 
 
(X) 
Diary card provided 
 
 
  
X 
 
 
 
Diary card collection / review 
  
 
 
 
 
X 
 
Post vaccination assessment* 
X 
 
 
X 
 
 
 
AE evaluation / diary use 
 
X 
 
 
X 
 
 
AEs & SAEs reviewed 
 
 
X 
 
 
X 
 
End-of-study visit 
 
 
 
 
 
 
X 
Complete blood count (mL) 
3 
 
3 
3 
 
3 
3 
Antibodies IgG (ELISA) (mL) 
 3  
 
 3  
 3  
 
3 
3 
Anti-PT (neutralization) (mL) 
3 
 
3 
3 
 
3 
3 
Ficoll - PBMC freezing and 
plasma aliquots (mL) 
20 
 
20 
20 
 
20 
20 
Total blood draw (mL) 
29 
 
29 
29 
 
29 
29 
* After vaccination subjects will be observed for 30 minutes;  
Table 3. Schedule of Assessment 
 

 
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ABBREVIATIONS AND DEFINITIONS 
AE 
Adverse event 
aP-vaccine 
Acellular pertussis vaccine 
AR 
Adverse reaction 
BNA 
BioNet-Asia Co., Ltd. 
CHO  
Chinese hamster ovary cell (CHO cell) assay 
ClinO 
Clinical trials ordinance (Ordonnance sur les essais cliniques) 
CRC 
Centre de Recherche Clinique 
CRF 
Case report form 
CTU 
Clinical trial unit 
dT 
Diphtheria – Tetanus  
dTpa 
Diphtheria – Tetanus – acellular pertussis 
Tdap 
Tetanus – diphtheria – acellular pertussis 
EC 
Ethics committee 
ELISA 
Enzyme-linked immunosorbent assay 
ELISPOT 
Enzyme-linked immunospot 
GCP 
Good clinical practice 
GMO 
Genetically modified organism 
GMT 
Geometric mean titer 
GMC 
Geometric mean concentration 
GP  
General Practitioner 
HUG 
Hôpitaux Universitaires de Genève 
ICF 
Informed consent form 
IMP 
Investigational medicinal product 
ITT 
Intention to treat 
NSAID 
Non-steroidal anti-inflammatory drug 
PBMC 
Peripheral blood mononuclear cells 
PI 
 
Principal Investigator 
PII 
Personally identifiable information 
PIS 
Participant information sheet 
PT 
Pertussis toxin 
rANOVA 
Repeated measure analysis of variance 
rPT 
Genetically detoxified pertussis toxin 
SADR 
Serious adverse drug reaction (also SAR) 
SAE 
Serious adverse event 
SOP 
Standard operating procedure 
SUSAR 
Suspected unexpected serious adverse reaction 
TGFb 
Transforming growth factor beta 
TNF 
Tumor necrosis factor 
WNL 
Within normal limits  
 
 

 
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1 BACKGROUND AND RATIONALE 
1.1 The recurrence of pertussis and need for optimized pertussis vaccines 
Pertussis is an important cause of infant death worldwide and continues to be a public health concern 
even in countries with high vaccination coverage. Estimates from WHO suggest that, in 2008, about 
16 million cases of pertussis occurred worldwide, 95% of which were in developing countries, and that 
about 195,000 children died from the disease (World Health Organization, 2010). Immunization 
programs designed to protect young children against Bordetella pertussis started in 1944 (Cherry JD, 
1999). The incidence of pertussis has been greatly reduced by mass vaccination, but even in countries 
with high vaccination coverage, the disease is still present (Centers for Disease Control and Prevention, 
1993; Christie CD et al, 1994). In a cross-sectional study published in 2000 the prevalence of antibodies 
to pertussis toxin reached 52% in the 30 to 39 year age group, without a further increase thereafter 
(Garcia-Corbeira P et al, 2000). 
These data suggest that there is a widespread circulation of the organism in the population and that 
pertussis infection is increasingly frequent in adolescents and young adults – which now represent the 
majority of cases. Although hospitalization, complications and mortality in adolescents and adults are 
rare, these populations serve as a reservoir for B. pertussis and play an important role in the 
transmission to the very young infants (Black S, 1997; Guris D et al, 1999; Althouse BM & Scarpino SV, 
2015). 
These observations have important implications for B. pertussis vaccination policy. In November 2012, 
the WHO Strategic Advisory Group of Experts (SAGE) on immunization expressed concern about 
resurgence of pertussis despite high vaccine coverage with aP vaccines. As pertussis immunity acquired 
through immunization or even infection is short-lived, its maintenance or reactivation requires repeat 
boosting. In 2014, WHO specified that the countries currently using an aP vaccine may continue using 
this vaccine but should consider the need for additional booster doses and strategies to prevent early 
childhood mortality in case of resurgence of pertussis (World Health Organization, 2014a). Countries 
with demonstrable nosocomial transmission are encouraged to vaccinate health-care workers, 
particularly maternity and pediatric staff, if economically and logistically feasible (World Health 
Organization, 2014b).  
A puzzling observation is that the efficacy of current acellular pertussis vaccines (which contain 
chemically-detoxified pertussis toxoid (PT) is higher in infants and children than in adolescents, in 
whom vaccine efficacy is limited and rapidly wanes. A recent publication about the 2012 US 
Washington state pertussis epidemic showed that protection wanes within 2 to 4 years after 
adolescent boosting, where the vaccine effectiveness declined to 34% (Acosta AM et al, 2015).  
The resurgence of pertussis is considered as resulting largely from the limited durability of aP-
vaccine-induced immunity in adolescents. This may derive – at least in part – from priming and 
repeat immunizations with acellular vaccines containing chemically-detoxified PT and thus the 
induction of antibodies specific of the chemically-detoxified PT but unable to efficiently recognize 
the native PT expressed by B. pertussis.  
The development of optimized acellular pertussis vaccines should thus include antigens with a similar 
immunogenicity profile as native PT but deprived of its toxic properties. This is best achieved through 
the genetic rather than chemical detoxification of PT, which results in nontoxic and immunogenic PT. 
1.2 Clinical evidence to date: development of aP vaccines including genetically-detoxified PT 
The development of optimized acellular pertussis vaccines should include the use of antigens with a 
similar immunogenicity profile as native Pertussis Toxin (PT) but deprived of its toxic properties. This 
is best achieved through genetic rather than chemical detoxification, which results in both nontoxic 
and optimally immunogenic PT. 

 
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In adults, children and toddlers below one year, the safety and immunogenicity of a 9K/129G 
genetically-detoxified rPT was first demonstrated with either a monovalent PT vaccine 
(15 µg/intramuscular) or in DTaP combined vaccine trials (Rappuoli R, 1999; Podda A et al, 1993). A 
comparative study with either monovalent pertussis vaccine, combined acellular vaccine or combined 
genetically detoxified PT vaccine showed a similar safety profile between all vaccine products. In this 
study, the genetically detoxified vaccine was the most immunogenic when similar PT dose levels were 
compared (Keitel WA et al, 1999). In infants, aP vaccines containing genetically-detoxified recombinant 
PT (rPT) were shown to be safe, highly immunogenic, efficacious and able to elicit antibodies and 
protection which persisted up to 6 years (Greco D 1996; Salmaso S 2001). The superior immune 
response of rPT-containing vaccines was associated with the conservation of 75-80% of native PT, 
allowing efficient binding of immune cells to B and T cell epitopes (Ibsen PH 1996; Di Tommaso A 1994). 
The development of this first generation vaccine was unfortunately interrupted by patent issues.  
Thus, genetically detoxified rPT was proven safe, immunogenic and effective in several clinical trials. 
 
1.2.1 Phase I/II study of BNA rPT-containing vaccines in healthy adults 
Following the expiration of the patents, BioNet-Asia developed a new B. pertussis strain expressing a 
recombinant PT (rPT) (Buasri W et al, 2012) which retains the functional antigenic properties of native 
PT but with loss of its toxicity. 
This genetically-detoxified recombinant PT (rPT) (Buasri W et al, 2012)was used in a Phase I/II 
randomized, observed-blind, controlled study conducted by BioNet-Asia in 2014 to assess the safety 
and immunogenicity of BNA aP vaccine containing rPT, FHA and PRN given alone or in combination 
with tetanus-diphtheria vaccine in adults (Protocol No. TDA101). A total of 60 healthy volunteers aged 
18-35 years were enrolled and randomized in a 1:1:1 ratio to receive BNA aP vaccine, BNA Tdap vaccine 
(both with genetically inactivated PT) or a marketed Tdap vaccine (Adacel®, Sanofi Pasteur), which is a 
chemically inactivated vaccine – see Investigator’s Brochure. 
The evaluated safety endpoints included local and systemic post-immunization reactions, adverse 
events, and serious adverse events within 28 days after vaccination. None of the subjects showed any 
clinical relevant modification of the complete blood count, erythrocyte sedimentation rate, renal and 
liver function tests and ECG, as reported by the investigator. None of the subjects had any immediate 
reaction within the 4-hour observation period after vaccination. Similar incidence of local and systemic 
post-immunization reactions was observed among the three vaccine groups, with one subject in the 
BNA Tdap group reporting local induration of Grade 3 severity which resolved without sequelae before 
study end. 
The incidence of Adverse Events (AEs) for 28 days after vaccination was similar in the three vaccine 
groups. Those related to vaccine administration were mostly local post-immunization reactions. All AEs 
were resolved without sequelae. One Serious Adverse Event (SAE) (‘dysfunctional uterine bleeding’) 
reported as unrelated to the study vaccine administration occurred in a female subject in the BNA aP 
vaccine group approximately two weeks after vaccination.  
Thus, BNA aP and Tdap vaccines showed a similar tolerability and safety profiles to the marketed 
vaccine in healthy adults. 
The immunogenicity endpoints were the antibody response on Days 7 and 28 post vaccination, 
including seroresponse rates and antibody titers to pertussis antigens, diphtheria and tetanus, as well 
as functional antibody titers - determining PT neutralizing antibody titer in CHO cell assay. Briefly, for 
PT: on Day 28 after vaccination, ELISA anti-PT geometric mean antibody titers (GMTs) as well as PT 
neutralizing antibody GMTs were statistically significantly higher in the BNA aP and Tdap groups than 
those in the marketed vaccine group (Figure 2). 
GMT ELISA Anti-PT Antibody 
 
 
GMT Anti-PT Neutralizing Antibody 

 
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Figure 2. Binding (left) or neutralizing (right) anti-PT IgG antibodies before and after immunization with BNA 
aPor Tdap vaccines or Adacel® 
Thus, BNA aP (Pertagen®) and Tdap vaccines elicited statistically significant higher antibody titers to 
PT, as measured by ELISA or by the CHO cell assay for the quantification of neutralizing antibodies.  
 
1.2.1 Phase II/III study in Thai adolescents 
BNA’s TdaP and aP (Pertagen®) vaccines were subsequently tested and compared to the licensed 
Sanofi Pasteur Adacel® vaccine in 450 (150 per each vaccine group) healthy 12-17 years old subjects in 
Bangkok, Thailand (BioNet TDA202). In this country, whole-cell vaccines are used for priming and 
acellular vaccines have not yet been introduced as childhood boosters.  
Preliminary results indicate similar frequencies and intensities of local and systemic solicited adverse 
reactions during 7 days after immunization and of adverse events during 28 days (see Investigator’s 
Brochure). A single SAE was reported, unrelated to study vaccines. 
 
Seroresponse rates (percentages of subjects with ≥ 4-fold increase of anti-PT titers) were 96%, 97% 
and 55% following immunization with BNA aP (Pertagen®), BNA TdaP (Boostagen®) and Adacel®, 
respectively. Superior seroconversion rates were also observed for FHA. 
 
This reflected the induction of significantly higher anti-PT and anti-FHA antibodies (Table 4). 
 
A. ELISA anti-PT GMCs by study groups 
Vaccine 
Baseline 
Day 28 post-vaccination 
Geometric Mean Change 
P-value 
GMT (IU/mL) 
(95% CI) 
GMT (IU/mL) 
(95% CI) 
GMT (IU/mL) 
(95% CI) 
BNA aP 
13.64 
(11.55-16.11) 
561.87 
(467.79-674.86) 
527.51 
(435.57-638.87) 
<0.0001* 
BNA TdaP 
12.91 
(11.24-14.83) 
365.23 
(315.07-423.38) 
343.08 
(294.46-399.73) 
<0.0001* 
Adacel® 
15.57 
(13.21-18.36) 
63.26 
(51.05-78.37) 
48.09 
(36.99-62.50) 
<0.0001* 
P-value 
0.3631 
<0.0001* 
<0.0001* 
  
 
 
 
 
 
 
 
 
0
50
100
150
200
250
300
BNA aP
BNA Tdap
Adacel®
GMT (ELISA) IU/mL
Baseline
Day 7
Day 28
0
20
40
60
80
100
120
140
160
BNA aP
BNA Tdap
Adacel®
PT NAb titer (CHO cell assay) 
IU/mL
Baseline
Day 7
Day 28

 
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B. ELISA anti-FHA GMCs by study groups 
Vaccine 
Baseline 
Day 28 post-vaccination 
Geometric Mean Change 
P-value 
GMT (IU/mL) 
(95% CI) 
GMT (IU/mL) 
(95% CI) 
GMT (IU/mL) 
(95% CI) 
BNA aP 
38.99 
(32.54-46.72) 
923.80 
(809.39-1054.4) 
836.13 
(725.13-964.12) 
<0.0001* 
BNA TdaP 
41.42 
(34.60-49.58) 
632.11 
(549.85-726.67) 
549.67 
(471.95-640.18) 
<0.0001* 
Adacel® 
45.71 
(37.64-55.50) 
241.85 
(208.86-280.05) 
178.19 
(148.94-213.19) 
<0.0001* 
P-value 
0.5369 
<0.0001* 
<0.0001* 
  
C. Neutralizing anti-PT ELISA GMCs by study groups in a subset of 50 subjects 
Vaccine 
Baseline 
Day 28 post-vaccination Geometric Mean Change 
P-value 
GMT (IU/mL) 
(95% CI) 
GMT (IU/mL) 
(95% CI) 
GMT (IU/mL) 
(95% CI) 
BNA aP 
9.75 
(7.23-13.14) 
275.74 
(181.63-418.59) 
309.08 
(214.09-446.23) 
<0.0001* 
BNA TdaP 
7.93 
(6.13-10.27) 
215.92 
(164.16-284.02) 
201.27 
(151.11-268.09) 
<0.0001* 
Adacel® 
8.83 
(6.50-12.01) 
36.26 
(25.74-51.08) 
33.66 
(24.36-46.52) 
<0.0001* 
P-value 
0.7993 
<0.0001* 
<0.0001* 
  
Table 4. Anti-PT and anti-FHA antibodies by study groups 
Thus, BNA aP (Pertagen®) and Tdap vaccines elicited similar reactogenicity and significantly higher 
antibody responses to PT and FHA in 12-17 year-old Thai adolescents who had been primed in 
childhood with whole-cell vaccines. 
Additional information is available in the Investigator’s Brochure. 
1.3 Rationale for the current study and proposed vaccine schedule 
The superior responses to rPT-containing BNA vaccines observed in Thai adults and adolescents 
strongly suggest a higher immunogenicity of the BNA genetically-detoxified rPT antigen. Importantly, 
however, this superior immunogenicity was observed in adults (Phase I/II) and adolescents (Phase II/III) 
who had been primed as infants with whole-cell pertussis vaccines – i.e. with inactivated vaccines 
containing native PT. In Switzerland, Europe and the US, the use of whole-cell vaccines for pertussis 
priming was replaced in 2000 by the use of the better tolerated acellular vaccines – which contain 
chemically-detoxified PT (aP). 
 
A previous Geneva study (Blanchard Rohner et al. CID 2019) reported that boosting aP-primed 
adolescents with one dose of the rPT-containing vaccine (Pertagen®) was well tolerated and elicited 2-
fold stronger anti-PT neutralizing and binding antibody responses than a sixth dose of cd/Tdap. 
However, this superior immunogenicity was found to be transient; a potential solution being repeat 
doses of the rPT-containing BNA vaccine.  

 
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Figure 3. Antibody responses to recombinant acellular pertussis vaccine (r-aP Pertagen®) compared to the 
standard vaccine containing chemically detoxified pertussis toxin (cd/Tdap Boostrix®) 
 
Figure 4. Memory B-cell response to recombinant acellullar pertussis vaccine (r-aP Pertagen®) compared to the 
standard vaccine containing chemically detoxified pertussis toxin (cd/Tdap Boostrix®) 
 
The critical question to be addressed here is whether two doses of rPT/FHA will prove to be more 
effective than one dose in adults previously exposed to at least 5 doses (2 months, 4 months, 12 
months, 4-7 years and 11-14/15 years) of chemically-detoxified PT-containing vaccines. This question 
is fundamental to define the potential of repeat doses of rPT/FHA to overcome the limited and rapidly 
waning efficacy of PT-containing boosters in adults.  
 
We therefore propose to assess the safety and immunogenicity of two doses of BNA aP (Pertagen®) 
administered at a 6 month interval to adults 18-30 years old previously primed with 5 doses of 
chemically-inactivated acellular pertussis vaccines and to compare the results with responses elicited 
by a single dose of BNA aP (Pertagen®) in the same population.  
2 OBJECTIVES AND ENDPOINTS 
2.1 Primary objective 
The primary objective is to assess the immunogenicity of two doses compared to a single dose of an 
acellular pertussis vaccine (Pertagen®) including genetically-detoxified pertussis toxin (rPT) 
administered at 6 months interval and delivered by the intramuscular route to adults aged 18-30 years 
previously primed and boosted with chemically-detoxified PT. 
 
 
 
2.1.1 Primary outcome measures 

 
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The main immunogenicity endpoints will be the geometric mean concentration (GMC) of neutralizing 
antibodies to PT. 
2.2 Secondary objectives 
 
To assess the safety of two doses at 6 months interval of intramuscular immunization with 
Pertagen® administered to adults, compared to one dose of Pertagen®. 
 
To assess the humoral responses elicited by two doses of Pertagen® when administered to adults, 
compared to one single dose. 
  
2.2.1 Safety outcome 
Genetically detoxified rPT was proven safe in several clinical trials (see 1.2 Clinical development of aP 
vaccines including genetically-detoxified PT). 
Solicited local and systemic reactions will be recorded on a diary card during 7 days and unsolicited 
AEs for 28 days after immunization.  
 
2.2.2 Main secondary immunogenicity outcomes 
The following parameters will be assessed at Day 0, Day 28 and Month 6 post first and second 
vaccination: 
 
Geometric mean concentrations (GMCs) of PT, FHA, tetanus and diphtheria-toxoid specific IgG 
antibodies measured by ELISA. 
 
Seroresponse rates of PT, FHA, tetanus and diphtheria-toxoid specific IgG antibodies measured by 
ELISA. 
 
Seroresponse rates of PT specific neutralizing antibodies. 
 
2.3 Exploratory Outcomes Measures 
Exploratory immunological measures will be performed at each visit pending sufficient or additional 
funding.  
These are anticipated to include: 
 
The assessment of antibody titers to specific neutralizing and non-neutralizing epitopes of PT, by 
competitive ELISA, following one for two doses of Pertagen® 
 
To compare antibody avidity following one or two doses of Pertagen® 
 
To assess the frequency and phenotype of PT-specific memory B cell responses following one or 
two doses of Pertagen®  
Exploratory immunological measures and the quantification of neutralizing anti-PT antibodies will 
involve collaboration with other specialized laboratories and research groups in Switzerland and/or 
abroad. This will involve transfer of coded serum/plasma and/or frozen peripheral blood mononuclear 
cells (PBMC) samples, traceable only by means of a subject identifier and as described in the signed 
informed consent form.  

 
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3 CLINICAL STUDY MATERIALS 
3.1 Study vaccines 
Two vaccines will be used in the study. The BNA study vaccine (Pertagen®) and the control vaccine 
(Revaxis®). 
 
Group A 
Revaxis® + Pertagen® 
50 subjects 
Group B 
Pertagen® + Pertagen® 
50 subjects 
Table 1. Study groups 
 
 
Pertagen® 
Revaxis® 
Active substance 
Tetanus Toxoid (TT) 
- 
NLT 20IU 
Diphtheria Toxoid (DT) 
- 
NLT 2.0 IU 
Pertussis Toxoid (PT) 
5 µga 
- 
Filamentous 
Hemagglutinin (FHA) 
5 µg 
- 
Pertactin (PRN) 
- 
- 
Fimbriae type 2/3 
- 
- 
Inactivated polio viruses 
type 1-2-3  
- 
40U (type 1), 
8U (type 2), 
32U (type 3) 
Adjuvants 
Aluminum Hydroxide  
0.3 mg/dose 
0.35mg/dose 
Volume for Injection 
q.s. to 0.5 mL 
q.s. to 0.5 mL 
a: Recombinant Pertussis Toxin (rPT) 
Table 2. Vaccine composition of each dose of 0.5 mL presented in pre-filled syringe 
 
The investigational product Pertagen® will be manufactured, labeled, packaged and released for 
clinical use by BNA, in accordance with the requirements of Good Manufacturing Practices. The quality 
control standards and requirements for the investigational vaccine will be described in separate 
release protocols and the required approvals will have been obtained. One batch will be used for the 
entire study. 
The Revaxis® vaccine used in this study is commercially available in Switzerland and will be purchased 
for the study. One batch will be used for the entire study. 
 
3.2 Packaging, Labeling, and Storage of Vaccines 
Study vaccines will be provided in appropriate boxes. 
The investigational vaccine container and the syringe labels will contain the following information: 
Sponsor name, protocol number, vaccine code, storage instructions, and “For Clinical Study Use Only”. 
The licensed vaccines will be re-labeled according to the applicable local requirement. 
 
All study products will be stored in a safe, locked, and secure place with no access by unauthorized 
personnel. They will be kept in a refrigerator (+2C to +8C) and not be frozen. Storage temperature 
will be monitored every day.  

 
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3.3 Preparation and Administration 
Both Pertagen® and Revaxis® vaccines are presented in 0.5 mL pre-filled syringes to be administered 
by intramuscular injection in the non-dominant deltoid. 
 
The package containing the used syringe (empty syringe), and any vaccine dispensing form / document 
(if applicable) will be stored at study site until end of the study. 
 
3.4 Clinical Study Supply, Dispensing, and Accountability 
All study products will be provided by BNA and shipped to the study site. Shipment content and 
condition (including temperature control) will be checked at reception. All study products used in the 
study will be accounted for in a Study Vaccine Accountability Record indicating the date of 
administration to the subject. 
 
An additional quantity of each vaccine will be supplied. In case a syringe of vaccine is broken or 
unusable, the unblinded site staff will replace it. Documentation of the use of the replacement syringe 
and reason for using it will be recorded by the site staff. 
 
At the end of the study, all unused vaccines will be, at BNA’s option, either returned to BNA or 
destroyed in accordance with written instructions provided by BNA. If to be returned, a shipment will 
be recorded, identifying each syringe being included in the shipment. The used study vaccines will be 
destroyed at study site according to the procedure of study site institution. 
4 STUDY DESIGN 
4.1 Overall Study Design 
This is a phase II/III randomized, double-blind controlled study to compare the safety and 
immunogenicity of 1 or 2 doses of acellular pertussis vaccines containing genetically-detoxified 
pertussis toxin in adults aged 18-30 years, previously primed and boosted with acellular pertussis 
vaccines.  
 
Figure 1. Study Flow Chart 

 
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4.2 Study population and entry criteria 
The study population will include adults aged 18-30 years previously primed and boosted with acellular 
pertussis vaccines (see entry criteria below). 
 
A leaflet describing the study objectives and modalities will be prepared to advertise the study to 
medical students of the University of Geneva, as well as other faculties if deemed necessary. An email 
containing the same information will also be sent out to the students’ mailing list. Potentially 
interested volunteers will be invited to contact the study staff. 
 
4.2.1 Informed consent 
The participant information form will be made available to these potential volunteers in advance such 
that they have ample time and opportunity to inquire about details of the trial and to decide whether 
or not to participate. Consenting participants must sign and date the informed consent form before 
any study-specific procedures may be performed.  
 
At the first visit, the volunteer will be fully informed of all aspects of the trial, the potential risks and 
their obligations. The following general principles will be emphasized: 
 
Participation in the study is entirely voluntary; 
 
Refusal to participate involves no penalty or loss of medical benefits; 
 
The volunteer may withdraw from the study at any time, without supplying a reason for 
withdrawal; 
 
The volunteer is free to ask questions at any time to allow him or her to understand the 
purpose of the study and the procedures involved; 
 
The study involves research on an investigational vaccine; 
 
The volunteer’s primary care practitioner may be contacted to corroborate their medical 
history or seek additional information; 
 
The volunteer’s blood samples taken as part of the study will be anonymized and stored for a 
period of 15 years. 
The aims of the study and all tests to be carried out will be explained. The volunteer will be given the 
opportunity to ask about details of the trial, and will then have time to consider whether or not to 
participate. If the volunteer does decide to participate, he or she will sign and date two copies of the 
consent form, one for his/her personal records, and one to be stored at site in the source documents. 
These forms will also be signed and dated by the Investigator. 
 
4.2.2 Inclusion and exclusion criteria 
This study will be conducted in adults aged 18-30 years, who meet the following inclusion and exclusion 
criteria:  
 
Inclusion criteria 
The volunteer must satisfy the following criteria to be eligible for the study: 
 
Has provided written informed consent before enrollment; 
 
Male or female, ages 18-30 years (inclusive) at the time of enrollment; 
 
With documented history of acellular pertussis immunization (5 doses); 
 
Free of clinically significant health problems, as determined by pertinent medical history and 
clinical examination at study screening; 
 
Non-pregnant, non-lactating female : 

 
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o This implies a negative urinary pregnancy test at enrolment; 
o If sexually active, female subjects must be willing to use reliable birth control measures for 
1 month after vaccination; 
 
Able to attend all scheduled visits and to understand and comply with the study procedures. 
 
Exclusion criteria 
The volunteer may not enter the study if any of the following apply:  
 
Prior dTpa immunization within the last 5 years or prior dT immunization within the last 2 years, 
or any other investigational vaccine likely to impact on interpretation of the trial data, as judged 
by the Principal Investigator; 
 
Suspected or confirmed pertussis infection within the last 10 years or documented pertussis 
infection in a household member within the last 10 years; 
 
History of severe local or systemic reactions to any vaccination or a history of severe allergic 
reactions; 
 
Known hypersensitivity or allergy to diphtheria, tetanus, or pertussis vaccine (including excipients); 
 
Receipt of investigational product up to 30 days prior to enrollment or ongoing participation in 
another interventional clinical trial; 
 
Receipt of licensed vaccines within 30 days of planned study immunization or ongoing 
participation in another clinical interventional trial; 
 
Acute or chronic, clinically significant psychiatric, hematologic, pulmonary, cardiovascular, or 
hepatic or renal functional abnormality as determined by the Investigator based on medical 
history, physical exam; 
 
Any confirmed or suspected immunosuppressive or immunodeficient condition, including human 
immunodeficiency virus (HIV) infection, asplenia, cytotoxic therapy in the previous 5 years, and/or 
diabetes; 
 
Any chronic or active neurologic disorder, including seizures, and epilepsy, excluding febrile 
seizures as a child; 
 
Has a known history of vaccine-induces Guillain-Barré Syndrome; 
 
Has an active malignancy or recent (<10 years) history of metastatic or hematologic malignancy; 
 
Suspected or known alcohol and/or illicit drug abuse within the past 5 years; 
 
Pregnant or lactating female, or female who intends to become pregnant during the study period; 
 
Administration of immunoglobulins and/or any blood products within the 120 days preceding 
study entry or planned administration during the study period; 
 
Receipt of chronic (>14 days) immunosuppressants or other immune-modifying drugs within 6 
months of study entry: 
o For corticosteroids, this will mean prednisone or equivalent ≥0.5 mg/kg/day, 
o Intranasal and topical steroids are allowed; 
 
Any other significant finding that, in the opinion of the investigator, would increase the risk of the 
individual’s having an adverse outcome by participating in this study. 
 
Temporary exclusion criteria at the time of randomization 
The following criteria constitute contraindications to administration of vaccine at that point in time; if 
any one of these occurs at the time scheduled for randomization, the subject may be randomized at a 
later date without the need for re-screening, at the discretion of the Investigator, or withdrawn at the 
discretion of the Investigator: 

 
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 
Acute disease at the time of randomization. (Acute disease in the context of this trial is defined as 
the presence of a moderate or severe illness with or without fever.) The vaccine/placebo can be 
administered to persons with a minor illness such as mild upper respiratory tract infection with or 
without low-grade febrile illness, i.e. temperature of ≤37.5°C; 
 
Body temperature ≥38°C within 3 days of the intended vaccination; 
 
Any other significant finding that, in the opinion of the investigator, would temporarily increase 
the risk of the individual’s having an adverse outcome by participating in this study. 
 
4.2.3 Compliance with dosing regimen 
The first intervention (study vaccine Pertagen® or Revaxis®) will be administered by the Clinical 
Investigator at Day 0, and the second (Pertagen®) at Day 180. At no time will the study medication be 
in the possession of the volunteer; compliance will not, therefore, be an issue.  
 
4.3 Randomization 
At Day 0, eligible subjects will be randomized in a 1:1 ratio into one of the following vaccine groups: 
 
Group A 
Revaxis® + Pertagen® 
50 subjects 
Group B 
Pertagen® + Pertagen® 
50 subjects 
Table 1. Study groups 
 
Randomization procedure 
Randomization allocation will be performed on a 1:1 basis generated by computer randomization, 
with a 10-block size, concealed in sequentially labeled opaque envelopes. Each participant will be 
assigned a unique treatment number that corresponds to his or her treatment allocation. Only the 
unblended immunizing nurses will have access to the treatment allocation. 
Randomization of subjects to treatment will occur at Visit 1 after all entry procedures have been 
performed and eligibility for the study confirmed. 100 volunteers will be allocated to either Group A 
or Group B at the ratio of 1:1 and will receive a 3-digit subject number preceded by the acronym of the 
study site (GE-_ _ _). The 3-digit subject number will be assigned according to the participant’s 
chronological order of enrollment at the site. The subject number will be used as the subject identifier 
throughout the study. 
Each participant will be randomized following the randomization list by chronological order and will be 
immunized according to the vaccine group assignment.  
Participants will be blinded in order to keep the double-blind design of the study. 
The personal responsible for study vaccine preparation, handling, storage and accountability, as well 
as immunization will be unblinded. 
The team responsible for assessing adverse events will be blinded.  
The laboratory staff performing the immunological assays will also be blinded. 
 
4.4 Formal safety analyses 
After vaccination, volunteers will be observed for 30 minutes at study site for any immediate post-
immunization reactions. Reactogenicity and safety will be assessed during study visits at the clinical 
trial unit (CTU) on Day 0 and Day 28 after the first immunization, on Day 180 and Day 210 after the 
second, and finally on Day 365. At Day 0 and Day 180 (Visit 1 and 3, vaccination days), a Diary Card will 
be distributed to study volunteer to record post-immunization local and systemic reactions and 
adverse events. At Day 28 and Day 210 (Visit 2 and 4), the investigator will reconcile and transcribe the 

 
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Diary Card information in their corresponding CRF. Post-immunization local and systemic reactions will 
be collected and monitored for 7 days after each vaccination. All adverse events, including SAEs, will 
be collected and monitored for 28 days after each vaccination (until Visit 2 and until Visit 4).  
 
 
 
 

 
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5 CONDUCT OF STUDY 
5.1 Study visits 
Participants will be asked to attend 5 scheduled visits at the Plateforme de Recherche Clinique de 
Pédiatrie, Gynécologie et Obstétrique (PGO) of the HUG. All subjects will be asked to remain in the 
study throughout its entire duration (one year). If a subject does not appear at a scheduled visit, every 
effort will be made to contact him or her to confirm that she/he is well and to reschedule the visit. This 
effort will be documented into the source data. Each study visit is described in detail below. An 
overview is found in Schedule of Assessment. 
 
Each visit is assigned a time point and a window period within which the visit will be conducted. 
Deviations from the window periods are to be avoided; however in some exceptional situations, they 
are permitted at the discretion of the Principal Investigator in the interest of completing the study 
schedule and obtaining subject safety and immunogenicity evaluations.  
 
5.1.1Visit 1: Randomization, assessment and immunization, Day 0 
Adults aged 18-30 years, male and female with no significant medical history or active illness will be 
recruited by the clinical investigators.  
 
Volunteers who consented and who have signed the informed consent will be screened for eligibility. 
 
The following activities will be performed during the first visit: 
 
Informed consent form (ICF) will be provided: 
o The volunteer will be allowed sufficient time for questions and answers and reflection 
as to whether or not they wish to participate; no further activity will take place until 
signing of ICF; 
 
Inclusion and exclusion criteria will be evaluated; 
 
Demographic data (including sex, birthdate, race) will be recorded; 
 
The medical history (including potential concomitant medication) will be reviewed; 
 
The female participants will be informed that the study is not open to subjects whom may be 
or become pregnant. A urinary pregnancy test will be performed and enrollment only 
confirmed if negative. They will also be reminded of the need to use birth control measures in 
case of sexual intercourse. 
 
In all subjects a physical examination will be performed (subject’s general appearance, skin, 
respiratory and cardiovascular function), as well as vital signs (blood pressure, heart rate, 
temperature, respiratory rate), weight, and height. 
 
Relevant information will be recorded in the site records and in the screening log. Each subject will 
receive a screening number; no personally identifiable information (PII) will be included in the paper 
CRF. During this process, no information will be recorded in the CRF. Completion of the CRF will only 
start after randomization and treatment application. 
 
Subjects remaining eligible for the study with no contraindication to treatment will then be 
randomized as described in 4.3 Randomization. 
 
 
29 mL of blood will be collected from all subjects for: 
o Complete blood count; 
o Anti-PT and anti-FHA IgG antibodies by ELISA; 
o Anti-diphtheria and anti-tetanus IgG antibodies by ELISA; 
o Anti-PT neutralizing IgG; 

 
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o Ficoll isolation and freezing of PBMCs with preservation and freezing of plasma 
aliquots; 
 
The treatment will be administered in a double-blind manner. All subjects will remain under 
close observation at the clinical trial unit (CTU) for 30 minutes; 
 
Subject will be given an emergency card with a phone number to call in case of questions or 
upon occurrence of any AE; 
 
The appointment for Visit 2 (Day 28) will be confirmed. 
 
Subjects must not leave the study site before the solicited and unsolicited AE check list has been 
reviewed for the 30 minutes after vaccination. Ongoing AEs at time of discharge will be reported on 
the diary to be fully assessed over 24 hours by the subject and also for the following days. Should an 
AE be ongoing at time of discharge, a phone interview will be scheduled for the following day. 
 
5.1.2Phone contact (Day 7 +/-1) 
Study participants will be contacted by phone at Day 7 to confirm that adverse reactions have 
subsided. Should this not be the case, an unscheduled visit will be considered appropriate. 
 
5.1.3Visit 2 (Day 28 +7) 
Study participants will be contacted by phone or mail a few days before Visit 2 to confirm the 
appointment and be reminded of the need to bring the diary card.  
 
The following activities will be performed during Visit 2: 
 
The diary card on solicited and unsolicited AEs, SAEs and concomitant medications will be 
discussed, verified and collected; 
 
AEs and SAEs will be recorded; 
 
29 mL of blood will be collected from all subjects for: 
o Complete blood count; 
o Anti-PT and anti-FHA IgG antibodies by ELISA; 
o Anti-diphtheria and anti-tetanus IgG antibodies by ELISA; 
o Anti-PT neutralizing IgG; 
o Ficoll isolation and freezing of PBMC with preservation and freezing of plasma 
aliquots; 
 
The appointment for Visit 3 (Day 180) will be confirmed.  
 
5.1.4Visit 3 (Day 180 +/- 30) 
Study participants will be contacted by phone or mail a few days before Visit 3 to confirm the 
appointment.  
 
The following activities will be performed during Visit 3: 
 
29 mL of blood will be collected from all subjects for: 
o Complete blood count; 
o Anti-PT and anti-FHA IgG antibodies by ELISA; 
o Anti-diphtheria and anti-tetanus IgG antibodies by ELISA; 
o Anti-PT neutralizing IgG; 
o Ficoll isolation and freezing of PBMCs with preservation and freezing of plasma 
aliquots; 
 
The treatment will be administered in a double-blind manner. All subjects will remain under 
close observation at the clinical trial unit (CTU) for 30 minutes; 
 
A diary card for recording daily symptoms will be explained and distributed to all subjects; 

 
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 
Subject will be given an emergency card with a phone number to call in case of questions or 
upon occurrence of any AE; 
 
The appointment for Visit 4 (Day 210) will be confirmed. 
 
5.1.5Phone contact (Day 187 +/-1) 
Study participants will be contacted by phone at Day 7 to confirm that adverse reactions have 
subsided. Should this not be the case, an unscheduled visit will be considered as appropriate. 
 
5.1.6Visit 4 (Day 210 +7) 
Study participants will be contacted by phone or mail a few days before Visit 4 to confirm the 
appointment and be reminded of the need to bring the diary card.  
 
The following activities will be performed during Visit 4: 
 
The diary card on solicited and unsolicited AEs, SAEs and concomitant medications will be 
discussed, verified and collected; 
 
AEs and SAEs will be recorded; 
 
29 mL of blood will be collected from all subjects for: 
o Complete blood count; 
o Anti-PT and anti-FHA IgG antibodies by ELISA; 
o Anti-diphtheria and anti-tetanus IgG antibodies by ELISA; 
o Anti-PT neutralizing IgG; 
o Ficoll isolation and freezing of PBMC with preservation and freezing of plasma 
aliquots; 
 
The appointment for Visit 5 (Day 365) will be confirmed. 
 
5.1.7Visit 5 (Day 365 +/- 30) 
Study participants will be contacted by phone or mail a few days before Visit 4 to confirm the 
appointment.  
 
The following activities will be performed during the final Visit: 
 
29 mL of blood will be collected from all subjects for: 
o Complete blood count; 
o Anti-PT and anti-FHA IgG antibodies by ELISA; 
o Anti-diphtheria and anti-tetanus IgG antibodies by ELISA; 
o Anti-PT neutralizing IgG; 
o Ficoll isolation and freezing of PBMC with preservation and freezing of plasma 
aliquots; 
 
Participants will be offered one dose of Revaxis® if needed for their protection. 
5.2 Unscheduled visits 
Subjects may contact the Clinical Investigator at any time for an unscheduled phone or on-site visit 
should they experience clinical symptoms or signs following treatment. At all unscheduled visits the 
following minimum will be performed: 
 
Questions concerning the history of the present illness as well as the subject’s general health; 
 
Medically attended AEs and any possible SAEs will be recorded; 
 
Any concomitant medication will be noted (any other vaccination is forbidden during the study 
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After eliciting the history of the present illness and performing any corresponding exams or laboratory 
tests, the Clinical Investigator will decide on the best course of treatment according to standard 
medical practice. 
5.3 Study assessments 
For each study subject, the blood volume taken per visit lies in the range of 29mL for immunologic 
assays. Blood will be taken on Day 0 and Day 180 (Baseline/vaccination days), as well as Day 28, Day 
210 and Day 365 (to assess the response to immunization). 
 
5.3.1 Safety tests 
Safety tests will include: 
 
Vital signs evaluation: heart and respiratory rates, systolic and diastolic blood pressure and 
axillary body temperature at baseline; 
 
Local and systemic reactivity assessed 30 minutes after vaccination at the Plateforme de 
Recherche Clinique PGO; 
 
Local and systemic reactivity assessed through diary cards, during 7 days after immunization; 
 
Other adverse events or serious adverse events during 28 days after immunization; 
 
Study Participants will be able to contact us at any time in case of any adverse event. 
 
5.3.2 Immunogenicity tests 
The immunogenicity of both Pertagen® + Pertagen® and Revaxis® + Pertagen® will be assessed in all 
subjects by ELISA-based detection of antigen-specific human IgG in serum samples. Sera will be 
assessed by the pertussis toxin neutralization assays to characterize the functionality of anti-PT 
antibodies. 
 
PBMCs will be frozen on site for subsequent analyses of the frequency and phenotype of specific B or 
T-cell responses before/after vaccination.  
 
6 STUDY DISCONTINUATION 
The study in its entirety may be discontinued prematurely with reasonable justification by the Principal 
Investigator (PI), Sponsor, Swissmedic or the Ethics Committee with oversight responsibilities at any 
time (see below), and/or individual subjects may terminate their participation prematurely, or have 
their participation be terminated by the Investigator. 
6.1 Study termination 
The PI, Sponsor, Swissmedic or the Ethics Committee with oversight responsibilities for the trial may 
terminate the trial at any time with reasonable justification. In the case of study termination, 
investigators will be informed of the procedures to be followed to ensure adequate consideration is 
given to the subject’s safety. 
 
The Investigator will be responsible for informing the Sponsor of the trial’s termination within 
24 hours, and, in accordance with art. 37 OClin, the Sponsor notifies Swissmedic within 7 calendar 
days. 
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In accordance with the principles of the current revision of the Declaration of Helsinki, a volunteer has 
the right to withdraw from the study at any time and for any reason, and is not obliged to give his or 
her reason(s) for doing so. The Investigator may withdraw the volunteer at any time in the interests of 
the volunteer’s health and well-being. In addition the volunteer may withdraw/be withdrawn for any 
of the following reasons: 
 
Ineligibility (either arising during the study or retrospectively, having been overlooked at 
screening); if the ineligibility is discovered after study application, the participant will be 
withdrawn from the study only in the event that the factor leading to ineligibility could directly 
jeopardize the health of the participant; 
 
Significant protocol deviation: failure to obtain informed consent prior to any study-specific 
test or procedure, or failure to follow protocol procedures that specifically relate to the 
primary safety and/or immunogenicity endpoints of the study; 
 
Volunteer 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. 
 
The reason for withdrawal will be recorded in the CRF. If withdrawal is due to an AE, appropriate 
follow-up visits or medical care will be arranged, with the agreement of the volunteer, until the AE has 
resolved, stabilized or a non-trial related causality has been assigned. Any volunteer who is withdrawn 
from the study may be replaced (see 6.3 Procedures for handling subjects with premature study 
discontinuation), if that is possible within the specified time frame (i.e., before the termination of study 
recruitment). The DSMB may recommend withdrawal of volunteers.  
 
Further stopping rules 
The Sponsor is entitled to terminate the study at any time for the following reasons: 
 
Negative criticism on the execution of the study. Upon signals that investigator did not react 
properly to complaints expressed by participants, violate the study protocol or perform 
unacceptably otherwise, the investigator(s) may be ‘frozen’ until further notice, to review the 
case; 
 
New data on the safety of the product under study that become known during the study that 
makes further use of the product undesirable, even in a controlled situation; 
 
Early results from the study that indicates failure or unsafety of the product under study; 
 
When investigators come into a situation that impedes the further progress of the study, the 
study may be discontinued if the investigator cannot be replaced or no other solution can be 
found. 
6.3 Procedures for 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. If a subject needs to be 
withdrawn, all efforts shall be made to follow safety of the subject as per protocol. 
 
Subjects who withdraw or are withdrawn from the study prior to treatment application will be 
replaced. No follow-up of these subjects will be performed and no data will be analyzed. Subjects 
withdrawing or withdrawn after treatment application will not be replaced if study recruitment has 
already been terminated, and their data will be analyzed under the intention-to-treat (ITT) principle. 
 

 
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 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 CRF as follows: 
 
Adverse event (specify); 
 
Death; 
 
Protocol violation (specify); 
 
Medical condition (specify); 
 
Consent withdrawal, not due to AE; 
 
Other (specify). 
6.4 Breaking the randomization code 
The treatment codes will be held separately from the clinical investigators in charge of assessing the 
occurrence of adverse events and breaking the blind will be done only at study end.  
Breaking the blind for a single subject will be considered when knowledge of the treatment assignment 
is deemed essential by the subject's physician for the subject's care. 
Additionally, in the event of a SUSAR or a holding rule activation, the blind may be broken for the 
purposes of reporting to Swissmedic and/or determination of trial feasibility, respectively. Any 
intentional or unintentional breaking of the blind will be reported and explained at the end of the trial, 
irrespective of the reason for its occurrence. The procedure and timing for revealing the treatment 
assignments will be documented as well. All calls resulting in an unblinding event will be recorded and 
reported by the IWRS to the Medical Monitor and the Sponsor. 
 
7 SAFETY ASSESSMENT 
Safety will be assessed by the frequency, incidence, severity and nature of adverse events and serious 
adverse events arising during the study. 
7.1 Adverse events 
An AE is any untoward medical occurrence in a subject that may occur during or after administration 
of an Investigational Medicinal Product (IMP) and does not necessarily have a causal relationship with 
the intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom or disease temporally associated with the study intervention, whether 
or not considered related to the study intervention. 
 
Each AE will be graded according to the tables for AE severity below (7.8 Assessment of severity). The 
following guidelines will be used to determine whether or not an AE is recorded in the study database: 
 
Solicited AE (i.e., reactogenicity parameters) will be recorded on diary cards in the 7 days and 
recorded in the CRF in the 7 days following treatment; 
 
Unsolicited AE of all severities will be recorded on diary cards in the 7 days and recorded in the 
CRF in the 28 days following treatment; 
 
SAE (as defined in 7.3 Serious adverse events) will be recorded in the CRF in the 28 days 
following treatment. 
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An adverse reaction (AR) is any untoward or unintended response to an IMP. This means that a causal 
relationship between the IMP and an AE is at least a reasonable possibility, i.e., the relationship cannot 
be ruled out. All cases judged by the reporting Investigator as having a reasonable suspected causal 
relationship to an IMP (i.e. possibly, probably or definitely related to an IMP) will qualify as AR. 
7.3 Serious adverse events 
A SAE is an AE that results in any of the following outcomes, whether or not considered related to the 
study intervention: 
 
Death; 
 
Life-threatening event (i.e., the subject was, in the view of the Investigator, at immediate risk 
of death from the event that occurred). This does not include an AE that, if it occurred in a 
more severe form, might have caused death; 
 
Persistent or significant disability or incapacity (i.e., substantial disruption of one’s ability to 
carry out normal life functions); 
 
Hospitalization, regardless of length of stay, even if it is a precautionary measure for continued 
observation. Hospitalization (including inpatient or outpatient hospitalization for an elective 
procedure) for a pre-existing condition that has not worsened unexpectedly does not 
constitute a SAE; 
 
An important medical event (that may not cause death, be life-threatening, or require 
hospitalization) that may, based upon appropriate medical judgment, jeopardize the subject 
and/or require medical or surgical intervention to prevent one of the outcomes listed above. 
Examples of such medical events include allergic reaction requiring intensive care in an 
emergency room or clinic, blood dyscrasias, or convulsions that do not result in inpatient 
hospitalization; 
 
Congenital anomaly or birth defect. 
7.4 Serious adverse drug reaction (SADR) 
An event that is expected or unexpected and 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, is considered a serious adverse drug reaction 
(SADR or SAR). 
7.5 Suspected unexpected serious adverse reaction (SUSAR) 
A SUSAR is an SAE that is unexpected and thought to be possibly, probably or definitely related to an 
IMP. No category of SAE has been defined as ‘expected.’ 
7.6 Causality assessment 
For every AE, an assessment of the relationship of the event to the administration of the vaccine will 
be undertaken. An intervention-related AE refers to an AE for which there is a probable or definite 
relationship to administration of a vaccine.  
 
The degree of certainty with which an AE can be attributed to administration of the study vaccine(s) 
(or alternative causes, e.g. natural history of the underlying diseases, concomitant therapy, etc.) will 
be determined by how well the event can be understood in terms of one or more of the following: 

 
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related 
suspicion that there is a relationship between vaccine and AE (without determining 
the extent of probability); there is a reasonable possibility that the vaccine 
contributed to the AE 
unrelated 
there is no suspicion that there is a relationship between vaccine and AE, there are 
other more likely causes and administration of the study vaccine is not suspected 
to have contributed to the AE 
 
The causality assessment will be made on the basis of the available information at the reporting time 
point and apply to both AEs and SAEs. Assessment of causality can change according to follow-up 
information.  
7.7 Reporting procedures for all adverse events 
All AEs and SAEs occurring within the 28 days following treatment and observed by the Investigator or 
reported by the volunteer, whether or not attributed to study intervention, will be recorded in the 
CRF. All AEs that result in a volunteer’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 volunteer 
consents to this). 
 
7.7.1 Reporting procedures for SAE 
Following the occurrence of any SAE, the trial subject’s randomization code may be broken if deemed 
necessary (see 6.4 Breaking the randomization code). The PI/Sponsor shall report the SAE to the CCER, 
BioNet-Asia Pharmacovigilance and Swissmedic, as soon as learning that the event meets the definition 
of a SAE and no later than 24h for fatal or life-threatening SAE and 7 calendar days for non-lethal SAE.  
The minimum information included in the initial SAE report will contain: subject’s number, date of 
birth, description of the event, study vaccine (date of vaccination), reporter information and causality 
assessment. 
Important follow-up information shall be reported when available. If relevant information is missing 
at the time of the initial SAE report, the reporter shall provide it in follow-up SAE report(s). A follow-
up report shall contain new, updated or corrected information. The follow-up report shall describe 
whether the event has resolved or continues, if and how it was treated including documentation of all 
supportive actions taken, and whether the blind was broken or not. 
 
7.7.2 Reporting procedures for SUSAR 
Following the occurrence of a SUSAR, the trial subject’s randomization code shall be broken (see 6.4 
Breaking the randomization code) and the PI shall report the event to the CCER, BioNet-Asia 
Pharmacovigilance and Swissmedic within 24h of learning that the event meets the definition of a 
SUSAR.  
 
 

 
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Figure 5. Workflow for reporting of serious adverse events and SUSAR 
7.8 Assessment of severity 
The severity of clinical and laboratory AE will be assessed according to the scales in Tables 5-7. 
 
Table 5. Toxicity grading scale for local adverse events 
£Grade 1a = when localized under the patch; †Grade 1b = mild but extending beyond the patch 
*In addition to grading the measured local reaction at the greatest single diameter, the measurement should be recorded 
as a continuous variable. 
**Induration/swelling should be evaluated and graded using the functional scale as well as the actual measurement. 
Adapted from the FDA’s 2007 voluntary guidance: 
http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/ 
Vaccines/ucm091977.pdf. 
 
Toxicity grading scale for local adverse events 
Local Reaction 
Grade 0 
Grade 1a£ 
 
Mild 
Grade 1b† 
 
Mild 
Grade 2 
 
Moderate 
Grade 3 
 
Severe 
Grade 4 
Potentially life-
threatening 
Redness/Erythema* 
None 
<25 mm 
25-50 mm 
51-100 mm 
>100 mm 
Necrosis or 
exfoliative 
dermatitis 
Swelling/Induration** 
None 
<25 mm 
25-50 mm and 
does not 
interfere with 
activity 
>50 mm or 
interferes with 
activity 
Prevents 
daily activity 
Necrosis 
Pain 
None 
- 
Does not 
interfere with 
activity 
Interferes with 
activity  
Prevents 
daily activity  
Emergency 
room visit or 
hospitalization 

 
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Table 6. Toxicity grading scale for Vital signs 
Vital signs 
Observation 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Fever (axillary) 
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-
urgent medical 
intervention indicated 
Urgent medical 
intervention indicated 
Life-threatening 
consequences, urgent 
intervention indicated 
Death 
Bradycardia 
(bpm)** 
Asymptomatic, 
intervention not 
indicated 
Symptomatic, medical 
intervention indicated 
Severe, medically 
significant, urgent 
medical intervention 
indicated 
Life-threatening 
consequences, urgent 
intervention indicated 
Death 
Hypertension** 
 
Prehypertension 
(systolic BP 
120 - 139 mm Hg 
or diastolic 
BP80 - 89 mm Hg) 
 
Stage 1 hypertension 
(systolic BP 
140 - 159 mm Hg or 
diastolic BP 
90 - 99 mm Hg); 
medical intervention 
indicated; recurrent 
or persistent (≥24h); 
symptomatic increase 
by >20 mm Hg 
(diastolic) or to 
>140/90 mm Hg if 
previously WNL; 
monotherapy 
indicated  
Stage 2 hypertension 
(systolic 
BP ≥160 mm Hg 
or diastolic 
BP ≥100 mm Hg); 
medical intervention 
indicated; more than 
one drug or more 
intensive therapy than 
previously used 
indicated  
Life-threatening 
consequences (e.g., 
malignant 
hypertension, 
transient or 
permanent neurologic 
deficit, hypertensive 
crisis); urgent 
intervention indicated  
Death 
Hypotension 
Asymptomatic, 
intervention not 
indicated 
Non-urgent medical 
intervention indicated 
Medical intervention 
or hospitalization 
indicated 
Life-threatening and 
urgent intervention 
indicated 
Death 
Definitions 
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 mm Hg. 
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 judgment 
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) 
 
 

 
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Table 7. Toxicity grading scale for systemic AEs excluding the vital signs listed above 
From the FDA’s 2007 voluntary guidance: 
(http://www.fda.gov/downloads/BiologicsBloodVaccines/GuidanceComplianceRegulatoryInformation/Guidances/ 
Vaccines/ucm091977.pdf) 
 
 
 
 
 
 
 
 
 
 
 
 
Toxicity grading scale for systemic adverse events 
Systemic 
sign/symptom 
Grade 1 
 
Mild 
Grade 2 
 
Moderate 
Grade 3 
 
Severe 
Grade 4 
Potentially 
life-threatening 
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 
requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or 
hospitalization 
Vomiting 
No interference with 
activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or 
hospitalization 
Abdominal Pain 
No interference with 
activity 
Some interference 
with activity not 
requiring medical 
intervention 
Prevents daily activity 
and requires medical 
intervention 
Medical consultation 
and/or 
hospitalization 
Diarrhea 
No interference with 
activity 
Some interference 
with activity not 
requiring medical 
intervention 
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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7.9 Summary of risk mitigation strategies 
The following risk mitigation strategies have been identified and will be implemented. 
Table 8. Risk mitigation strategies 
Individual risk 
Risk evaluation 
Identified risk mitigation strategies 
Suggested implementation 
Local allergic 
reaction 
Low risk. No known 
allergen included. 
 
Local cortical cream or 
antihistaminic treatment for 
symptom relief 
Anaphylactic 
reaction 
Low risk. No known 
allergen included. 
Exclusion of subjects with history of 
severe vaccine allergic reactions 
Surveillance of all subjects on site 
for 30 minutes after immunization. 
Strong / 
sustained 
inflammatory 
reactions 
Low risk: low 
reactogenicity of 
pertussis antigens.  
Paracetamol, NSAID 
Monitoring (Day 7 phone call) + 
emergency phone numbers. 
Indications on use of paracetamol 
and NSAID for symptom relief 
Direct 
pathogenicity of 
rPT  
Low risk: reduced toxicity 
(by a factor of 105- 106) 
compared to native PT  
Exclusion of potentially vulnerable 
populations (young children, 
pregnant women, etc.) 
None additional needed 
 
8 STATISTICAL ANALYSIS 
8.1 Sample size calculation 
This is a phase II/III randomized, double-blind controlled study to compare the safety and 
immunogenicity of one compared to two doses of acellular pertussis vaccines including genetically-
detoxified PT in adults previously immunized with chemically inactivated acellular pertussis vaccines. 
The sample size for this study is based on the previous study using the rPT vaccine in teenagers in 
Geneva (Blanchard Rohner et al. CID 2019). Where applicable, 2-sided test at the 5% significance level 
will be utilized with no multiplicity adjustment. P-values will be considered exploratory only. One 
hundred volunteers will be randomized in total, with 50 in each group.  
8.2 Safety analysis 
The safety analysis will include all randomized subjects who have received a dose of study vaccine. 
The overall percentage of subjects with at least one spontaneously reported adverse event, with date 
of onset up to 28 days after vaccination will be tabulated with exact 95% confidence intervals, by 
type of adverse event; by severity; and by causality. They will be displayed by vaccine group as both 
frequencies and percentages on the ITT data set. 
All reported adverse events that start post-vaccination will be tabulated. If a given disease is already 
reported as ongoing at the first visit on the medical history pages, it will be counted and tabulated as 
a vaccine emergent adverse event only if it worsens after the immunization with the study vaccine. 
Serious adverse events and discontinuation due to adverse event(s) will be described in detail by 
vaccine group. 
8.3 Immunogenicity analyses 
The primary immunogenicity endpoint will assess the immune response to two doses of Pertagen®, as 
compared to one dose, by measuring the Day 28 geometric mean concentration (GMC) of neutralizing 
antibodies to PT after immunization. 
The other immunogenicity end-points are listed in Section 2.2 of this protocol.  

 
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The following descriptive statistics will be provided for each variable: number of subjects, 
percentages, mean, geometric mean, standard deviation, median, minimum, maximum, and range.  
Immunogenicity endpoints and confidence bounds will be calculated for each group and compared 
(using Chi-square or Fisher’s exact test for binary endpoints, and Wilcoxon-Mann-Whitney’s test or 
Kruskal-Wallis test for quantitative endpoints). All tests will be two-sided. 
9 QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
9.1 Investigator procedures 
Approved site-specific SOPs will be used at clinical and laboratory sites. 
9.2 Monitoring 
Monitoring will be performed according to ICH Good Clinical Practice (GCP) by the Centre de Recherche 
Clinique (CRC) of the University Hospital of Geneva. Following a Monitoring Plan and written SOPs, the 
monitors will verify that the clinical trial is conducted and data are generated, documented and 
reported in compliance with the protocol, GCP and the applicable regulatory requirements. The CTU 
will provide direct access to all trial-related source data, documents and reports for the purpose of 
monitoring and inspection by local and regulatory authorities. 
9.3 Modification to protocol 
No substantial amendments to this protocol will be made without consultation with BNA. 
HUG/Sponsor will promptly inform BNA of any proposed amendment to the Protocol, in writing, and 
allow BNA to review and comment on the proposed amendment. However, for the avoidance of doubt, 
HUG/Sponsor shall have overall responsibility for finalizing the Protocol in accordance with the 
Applicable Requirements. 
 
The Principal Investigator is responsible for ensuring that changes to an approved trial, during the 
period for which regulatory and EC approval has already been given, are not initiated without 
regulatory and EC review and approval except to eliminate apparent immediate hazards to the subject. 
9.4 Protocol and GCP deviation 
Any deviations from the protocol and GCP will be documented in a protocol deviation form and filed 
in the trial master file. 
9.5 Trial progress 
The progress of the trial will be overseen by the Principal Investigator. 
9.6 Publication policy 
The investigators shall have the right, consistent with academic standards, to publish or present the 
results of the research work performed as described in this protocol. The investigators agree to 
appropriately acknowledge the source of the product and information as well as the contribution of 
any scientist from BNA, as appropriate. The Principal Investigator agrees that submission for 
publication of any results relating to this study may be undertaken only after the sponsor and other 
Consortium members have had thirty (30) working days to review the manuscript (fifteen (15) days for 
abstracts). 

 
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10 ETHICAL AND REGULATORY ASPECTS 
10.1 Declaration of Helsinki 
Study investigators will ensure that this study is conducted according to the principles of the latest 
revision of the Declaration of Helsinki (Fortaleza, Brazil, October 2013). 
10.2 ICH Guidelines for Good Clinical Practice (GCP) 
Study investigators will ensure that this study is conducted in full conformity with the ICH Good Clinical 
Practice (GCP), the requirements of the Swiss Human Research Act (HRA; 810.30, 2011) and the Swiss 
ordinance on clinical trials (ClinO; 810.305, 2013), and local regulatory requirements. 
10.3 Study registration 
The study will be registered in www.clinicaltrials.gov as soon as we have all authorizations to start the 
study. 
10.4 Categorization of study  
This Clinical Trial is under Category C, as it is evaluating the effects of a medicinal product that is 
authorized in other countries but not yet in Switzerland.  
10.5 Ethics committee and regulatory agency review 
The protocol, proposed ICF, and all other study documents, will be submitted to the Geneva Canton 
ethics committee and Swissmedic for approval. The Principal Investigator will submit and, where 
necessary, obtain approval from the EC and Swissmedic for all subsequent substantial amendments to 
the protocol and ICF. 
10.6 Declaration of interest 
The Principal Investigator and all co-investigators declare no conflict of interest in the concept and 
execution of this study.  
10.7 Informed consent 
Written, informed consent must be obtained before a volunteer can be enrolled, as described in 4.2.1 
Informed consent. The risks and benefits incurred by the volunteer’s participation will be stated clearly 
in the ICF and discussed directly with the volunteer before any enrollment can occur. 
10.8 Benefits and risks to the participant 
All the participants will receive an efficient pertussis immunization with a BNA® aP (Pertagen®) and 
Revaxis®, to ensure the recall of immunity against diphtheria, tetanus and the 3 pertussis antigens. 
Vaccine-induced immunity will be confirmed by serological analyses. 
The risks to the participant are the potential side effects of the vaccine, as described above, as well as 
the pain and bruising that may occur as a result of the blood draws described above. 
Participants will receive a compensation of 200 CHF for the inconvenience (time, blood draws, etc.). 
10.9 Subject confidentiality 
All data will be coded: subject data will be identified by a unique study number containing no 
personally identifiable information (PII) in the CRF and database. A separate confidential file containing 

 
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PII will be stored in a secured (locked) location in accordance with data protection requirements. Only 
the sponsor study investigators, the study monitor, the EC and regulatory authorities will have access 
to the records. Photographs taken of vaccination sites (if required, with the subject’s written, informed 
consent) will not include the subject’s face and will be identified by the date, trial code and subject’s 
unique identifier. Photographs will be stored as confidential records, as above. Again, with the 
subject’s written consent, this material may be shown to other professional staff, used for educational 
purposes, or included in a scientific publication.

 
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11 DATA HANDLING AND RECORD KEEPING 
11.1 Data handling and management 
The Principal Investigator will have the responsibility for overseeing the receiving, entering, cleaning, 
querying, analyzing and storing all data that accrue from the study by designated persons. Data 
handling and management will be performed by the Plateforme de Recherche Clinique PGO. 
Throughout regular data collection and monitoring, clinical data reported on CRFs and/or relevant 
serological results will be integrated into a trial database using TeleForm (http://www.cardiff-
teleform.com/). This includes safety data and outcome data. 
 
For each set of data, quality control and triggers to computerized logic and/or consistency checks will 
be systematically applied in order to detect errors or omissions. After integration of all corrections in 
the complete set of data, the database will be locked and saved before being released for final 
statistical analyses. Each step of this process will be monitored through the implementation of 
individual passwords and/or regular backups in order to maintain appropriate database access and to 
guarantee database integrity. 
11.2 Record keeping 
The Investigator will maintain appropriate medical and research records for this trial, in compliance 
with ICH E6 GCP and regulatory and institutional requirements for the protection of confidentiality of 
volunteers. The Principal Investigator, co-investigators and clinical research nurses will have access to 
records. Investigators will permit authorized representatives of the Sponsor, monitors, as well as 
ethical and regulatory agencies to examine (and when required by applicable law, to copy) clinical 
records for the purposes of monitoring, quality assurance reviews, audits and evaluation of the study 
safety and progress. 
11.3 Source data and case report forms (CRFs) 
All protocol-required information will be collected in source documents and/or entered into CRFs by 
study investigators. Source documents are original documents, data, and records from which the 
subject’s CRF data are obtained. For this study, these will include, but are not limited to, subject 
consent form, clinical notes (medical history, concomitant medication, copy of vaccination records, 
vital signs, physical examination, AE data), laboratory data (pregnancy test for females, hematology 
and immunology results), diaries, and correspondence. All source data and CRFs will be stored 
securely.  
 
The information to be recorded in the CRF is listed in detail in Box 1. The CRF accompanies this study 
protocol.  
 
Box 1. Subject information to be recorded in the CRF. 
 
Demographic information and habits: 
 
Sex 
 
Age 
 
Ethnicity 
Medical history and physical findings: 
 
Past medical and surgical history 
 
Any current medical conditions  
 
Occurrence of AE, solicited and unsolicited 

 
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 
Concomitant medications and other therapy 
 
The contents of the subject diary card (Days 0 – 7) 
 
Physical examination findings 
Results of laboratory and other analyses: 
 
Results of urine pregnancy screens, if applicable 
 
In the event of an AE, the results of any additional laboratory testing as determined clinically 
indicated and appropriate 
 
Note: The collection of information on ethnicity is routine practice in vaccine studies, as ethnicity 
may influence vaccine responses (Haralambieva et al. 2013 and 2014, Avnir et al. 2016) 
11.4 Data protection and ownership 
The study protocol, documentation, data and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorized third 
party. As delineated in the Collaboration Agreement between the Sponsor and Bionet Asia, the data 
generated throughout the course of the study will be owned by the Sponsor. 
11.5 Retention and destruction of study data and biological material 
Study data and biological material will be stored for 15 years after study termination. Thereafter, 
biological samples will be destroyed according to usual biosafety/laboratory, which include 
documentation of each sample and its destruction. There is currently no plan for further use of samples 
(biobanking). 
 

 
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12 FINANCING AND INSURANCE 
12.1 Financing 
This investigator-driven study is funded by private foundations and available research funds of the 
Centre for Vaccinology. BNA will provide the Study vaccine (Pertagen®) and assistance at no charge. A 
contract between HUG and BioNet-Asia Co., Ltd. is finalized and will be communicated as soon as 
signed. 
 
There will be no costs to the institution. 
12.2 Insurance 
Study insurance will be provided by the Sponsor. The finalized insurance policy will be solicited 
following reception of Ethical Authorization and forwarded as soon available – prior to study initiation.   
12.3 Compensation of subjects 
A compensation of 200 CHF will be offered to the subjects after completing all 5 visits. 
All study visits and related assays will be financed by the Sponsor, with no charge to the subjects or 
their healthcare insurance carriers. 

 
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