Phase 2b Study of BPZE1 Intranasal Pertussis Vaccine in Adults to Assess Immunological Response and Safety Profile of 1-Dose (Prime) and 2-Doses (Prime+Boost) Schedule, Compared to a Boostrix™ Prime Dose With or Without a BPZE1 Boost Dose
Phase: PHASE2
Conditions: Pertussis, Whooping Cough
Sponsor: ILiAD Biotechnologies

CLINICAL STUDY PROTOCOL 
A Phase 2b, Multi-Center, Placebo-Controlled, Randomized Study of 
BPZE1 Intranasal Pertussis Vaccine in Healthy Adults to Assess the 
Immunological Response and Safety Profile of Single Dose (Prime) and 
Two Doses (Prime + Boost) Schedule, and Compared to a Boostrix™ Prime 
Dose With or Without a BPZE1 Boost Dose 
IB-200P 
Sponsor: 
Sponsor Contact: 
Medical Monitor: 
Date of Original Protocol: 
Date of Amendment 1: 
Date of Amendment 2: 
Date of Amendment 3: 
Date of Amendment 4: 
Date of Amendment 5: 
ILiAD Biotechnologies 
4581 Weston Road, Suite 260 
Weston, FL 33331 
Chief Operating Officer 
Medical Monitor 
04 January 2018 (Version 1.0) 
06 March 2019 (Version 2.0) 
17 April 2019 (Version 3.0) 
15 May 2019 (Version 4.0) 
31 May 2019 (Version 5.0) 
20 November 2019 (Version 6.0) 
CONFIDENTIAL  
All financial and nonfinancial support for this study will be provided by ILiAD 
Biotechnologies. The concepts and information contained in this document or generated 
during the study are considered proprietary and may not be disclosed in whole or in part 
without the expressed, written consent of ILiAD Biotechnologies. 
The study will be conducted according to the International Council for Harmonisation 
harmonised tripartite guideline E6(R2): Good Clinical Practice.  

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Table of Contents 
Table of Contents ....................................................................................................................... 6
List of Tables ............................................................................................................................ 10
Protocol Synopsis..................................................................................................................... 11
List of Abbreviations................................................................................................................ 27
1
Introduction ...................................................................................................................... 29
1.1 
Background Information ......................................................................................... 29
1.2 
Rationale ................................................................................................................. 31
1.3 
Potential Risks and Benefits ................................................................................... 32
1.3.1
Potential Risks ......................................................................................... 32
1.3.2
Risks of Study Participation .................................................................... 33
1.3.3
BPZE1 Risks to Study Subjects ............................................................... 33
1.3.4
Risks to the Environment or Potential for Interaction With Wild-Type B. 
Pertussis Strains ....................................................................................... 34
1.3.5
Boostrix Risks to Study Subjects ............................................................. 36
1.3.6
Known Potential Benefits ........................................................................ 37
2
Study Objectives and Endpoints ...................................................................................... 38
2.1 
Primary Objectives.................................................................................................. 38
2.1.1
Primary Immunogenicity Objective......................................................... 38
2.1.2
Primary Safety Objective ......................................................................... 38
2.2 
Secondary Objectives.............................................................................................. 38
2.2.1
Secondary Immunogenicity Objectives ................................................... 38
2.2.2
Secondary Colonization Objectives ......................................................... 39
2.2.3
Secondary Safety Objectives ................................................................... 39
2.3 
Exploratory Objective ............................................................................................. 39
2.4 
Primary Endpoints .................................................................................................. 39
2.4.1
Primary Immunogenicity Endpoints ........................................................ 39
2.4.2
Primary Safety Endpoints ........................................................................ 40
2.5 
Secondary Endpoints .............................................................................................. 40
2.5.1
Secondary Systemic Immunogenicity Endpoints .................................... 40
2.5.2
Secondary Mucosal Immunogenicity Endpoints ..................................... 42

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2.5.3
Secondary Colonization Endpoints .......................................................... 43
2.5.4
Secondary Safety Endpoints .................................................................... 44
2.6
Exploratory Endpoint .............................................................................................. 44
3
Investigational Plan .......................................................................................................... 45
3.1
Study Design ........................................................................................................... 45
3.1.1 
Rationale of Study Design ....................................................................... 48
4
Subject Selection and Withdrawal Criteria ...................................................................... 50
4.1
Selection of Study Population ................................................................................. 50
4.1.1 
Inclusion Criteria ..................................................................................... 50
4.1.2 
Exclusion Criteria .................................................................................... 51
4.2
Withdrawal of Subjects From Study Treatment and/or the Study .......................... 54
4.2.1 
Reasons for Withdrawal/Discontinuation ................................................ 54
4.2.2 
Handling of Withdrawals ......................................................................... 55
4.2.3 
Replacements ........................................................................................... 56
5
Study Treatments .............................................................................................................. 56
5.1 
Method of Assigning Subjects to Treatment Groups .............................................. 56
5.2 
Treatments Administered ........................................................................................ 57
5.3 
Identity of Investigational Product.......................................................................... 58
5.3.1
Study Drug Packaging and Storage ......................................................... 59
5.3.2
Investigational Product Accountability .................................................... 60
5.3.3
Other Supplies.......................................................................................... 60
5.4
Overdose Management ........................................................................................... 61
5.4.1 
Treatment of Overdose ............................................................................ 61
5.5
Blinding................................................................................................................... 61
5.5.1
Breaking the Blind Due to Medical Emergency ...................................... 62
5.6
Treatment Compliance ............................................................................................ 62
5.7
Prior Vaccinations and Concomitant Therapy ........................................................ 62
6
Study Assessments and Procedures .................................................................................. 64
6.1
Demographic and Baseline Data ............................................................................. 64
6.2
Medical History ...................................................................................................... 64
6.2.1 
Concomitant Medication.......................................................................... 64

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6.3 
Safety Assessments ................................................................................................. 65
6.3.1
Vital Sign Measurements ......................................................................... 65
6.3.2
Post-vaccination Evaluation .................................................................... 65
6.3.3
Complete Physical Examination .............................................................. 66
6.3.4
Clinical Safety Laboratory Tests .............................................................. 66
6.3.4.1
Serology ................................................................................................... 67
6.3.4.2
Urine Drug Screen ................................................................................... 67
6.3.4.3
Urine Pregnancy Test ............................................................................... 67
6.3.5
Adverse Events ........................................................................................ 68
6.3.5.1
Definitions of Adverse Events ................................................................. 68
6.3.5.2
Serious Adverse Events ........................................................................... 68
6.3.5.3
Site-Specific and General Systemic Reactogenicity Symptoms.............. 68
6.3.5.4
Assessing and Documenting Adverse Events .......................................... 71
6.3.5.5
Reporting Adverse Events ....................................................................... 72
6.3.5.6
Reporting Serious Adverse Events .......................................................... 73
6.3.5.7
Suspected Unexpected Serious Adverse Reactions and Nonserious 
Adverse Events of Special Interest .......................................................... 73
6.3.5.8
Assessment of Severity ............................................................................ 74
6.3.5.9
Assessment of Causality .......................................................................... 74
6.3.5.10 Follow-up of Subjects Reporting Adverse Events ................................... 75
6.3.6
Immunogenicity Assessments .................................................................. 75
6.4
Halting Rules .......................................................................................................... 76
6.5
Pregnancy ................................................................................................................ 77
6.6
Laboratory Analyses ............................................................................................... 77
6.7
Sample Collections ................................................................................................. 78
7
Statistical and Analytical Plan .......................................................................................... 79
7.1
Primary Immunogenicity and Safety Endpoints ..................................................... 79
7.2
Secondary Immunogenicity and Safety Endpoints ................................................. 80
7.3
Exploratory Endpoints ............................................................................................ 84
7.4
Sample Size Calculations ........................................................................................ 84
7.5
Analysis Sets ........................................................................................................... 85
7.6
Description of Subgroups to be Analyzed .............................................................. 86
7.7
Statistical Analysis Methodology ........................................................................... 86

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7.7.1
Analysis of Primary Immunogenicity Endpoint ...................................... 87
7.7.2
Analysis of Primary Safety Endpoint ...................................................... 88
7.7.3
Analysis of Secondary Immunogenicity Endpoint .................................. 88
7.7.4
Analyses of Efficacy Endpoint ................................................................ 89
7.7.5
Analysis of Secondary Safety Endpoints ................................................. 89
7.7.6
Other Analyses ......................................................................................... 90
7.7.7
Interim Analyses ...................................................................................... 90
8
Data Quality Assurance .................................................................................................... 91
8.1
Data Management ................................................................................................... 91
9
Ethics ................................................................................................................................ 92
9.1
Institutional Review Board ..................................................................................... 92
9.2
Ethical Conduct of the Study .................................................................................. 92
9.3
Subject Information and Consent............................................................................ 92
10 Investigator’s Obligations ................................................................................................ 94
10.1 Confidentiality ........................................................................................................ 94
10.2 Financial Disclosure and Obligations ..................................................................... 94
10.3 Investigator Documentation .................................................................................... 95
10.4 Study Conduct ......................................................................................................... 96
10.5 Adherence to Protocol............................................................................................. 96
10.6 Adverse Events and Study Report Requirements ................................................... 96
10.7 Investigator’s Final Report ..................................................................................... 96
10.8 Records Retention ................................................................................................... 96
10.9 Publications ............................................................................................................. 97
11 Study Management ........................................................................................................... 98
11.1 Monitoring .............................................................................................................. 98
11.1.1
External Data Monitoring Committee ..................................................... 98
11.1.1.1 Safety Monitoring Committee ................................................................. 98
11.1.2
Monitoring of the Study ........................................................................... 99
11.1.3
Inspection of Records .............................................................................. 99
11.2 Management of Protocol Amendments and Deviations........................................ 100
11.2.1
Modification of the Protocol .................................................................. 100

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11.2.2
Protocol Deviations................................................................................ 100
11.3 Study Termination ................................................................................................. 101
11.4 Final Report .......................................................................................................... 101
12 Reference List................................................................................................................. 102
13 Appendices ..................................................................................................................... 104
13.1 Appendix: Schedule of Events .............................................................................. 104
13.2 Appendix: FDA Table for Laboratory Grading ..................................................... 108
13.3 Appendix: FDA Table for Vital Sign Grading ...................................................... 110
List of Tables 
Table 3-1
Dosing Scheme ............................................................................................... 45
Table 3-2
Dosing and Safety Lead-In Cohort ................................................................. 47
Table 6-1
Toxicity Grading Scales .................................................................................. 69
Table 7-1
95% Confidence Interval and Width for Selected Response Rate Assumptions 
for Relevant Treatment Arm Sample Sizes ..................................................... 85
Table 13-1
Schedule of Events ........................................................................................ 105
Table 13-2
Laboratory Abnormalities ............................................................................. 108
Table 13-3
Vital Sign Abnormality ..................................................................................110

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Protocol Synopsis 
Protocol 
Number: 
IB-200P 
Title: 
A Phase 2b, Multi-Center, Placebo-Controlled, Randomized Study of 
BPZE1 Intranasal Pertussis Vaccine in Healthy Adults to Assess the 
Immunological Response and Safety Profile of Single Dose (Prime) and 
Two Doses (Prime + Boost) Schedule, and Compared to a Boostrix™ 
Prime Dose With or Without a BPZE1 Boost Dose 
Sponsor: 
ILiAD Biotechnologies 
4581 Weston Road, Suite 260 
Weston, FL 33331 
Study Phase: 
2b 
Study Sites: 
3 to 5 clinical sites in the United States 
Indication: 
Pertussis in adults and adolescents 
Rationale: 
The availability of a cost-effective pertussis vaccine that provides 
improved efficacy and prolonged protection with the potential to reduce 
or eliminate transmission would present a breakthrough in the 
prevention of colonizing pertussis infections. This novel approach may 
not only protect BPZE1-vaccinated individuals from Bordetella 
pertussis infection but may also reduce the B. pertussis reservoir in the 
adult population. The ability to prevent colonization by wild type B. 
pertussis that enable transmission may facilitate substantial reduction in 
the incidence of pertussis in infants. 
The intranasally administered BPZE1 vaccine provides an opportunity 
to generate a locally effective mucosal antibody response at the site of 
potential exposure, and thereby mimics the route of entry of the wild 
type pathogen and results in a broader immune response (type 1 T helper 
cells, type 2 T helper cells, and nasal mucosal immune responses). The 
study population, healthy adults, has been chosen to maximize the 
quality of immunogenicity data while minimizing risk and potential 
safety signals.  
We hypothesize that the BPZE1 vaccine will be safe and induce nasal 
mucosal immunity beyond that observed with standard vaccination with 
Boostrix™ and that BPZE1 will also induce systemic immunity. 
Immunity will be measured in enzyme-linked immunosorbent assays 
(ELISA) specific for pertussis toxin (PT), filamentous hemagglutinin 
(FHA), pertactin (PRN), and fimbriae (FIM) 2/3, and a broader pertussis 
ELISA developed with BPZE1 whole cell extract. In addition, we 
hypothesize that a priming dose of intranasal BPZE1 vaccine will result 

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in fewer subjects colonized (eg, lower colony counts) following a 
boosting dose of BPZE1, whereas a priming dose of Boostrix will not 
reduce colonization following a boosting dose of BPZE1, ie, Boostrix 
will generate less nasal mucosal immunity to prevent colonization by the 
BPZE1 live attenuated B. pertussis strain. Lastly, given that the majority 
of the population has received pertussis vaccination on multiple 
occasions, this study will assess the safety and immune response of 
BPZE1 as booster delivered after a prime dose of Boostrix in an adult 
population. 
Objectives: 
Primary objectives 
Immunogenicity: 

To assess nasal mucosal secretion immune response (secretory
immunoglobulin A [S-IgA]) following intranasal vaccination with
BPZE1 (109 colony-forming units [CFU]) when used as a single
(eg, prime) or 2-dose (eg, prime + boost) series.
Safety 

To assess reactogenicity (all) and specific safety laboratory
parameters (safety lead-in cohort only) following intranasal
vaccination with BPZE1, either 107 CFU (safety lead-in cohort
only) or 109 CFU (safety lead-in cohort and full cohort), in healthy
adults.
Secondary Objectives 
Immunogenicity: 

To assess the systemic immune response (immunoglobulin G [IgG],
immunoglobulin A [IgA]) following intranasal vaccination with
BPZE1 when used as a single (eg, prime) or 2-dose (eg, prime +
boost) series.

To assess nasal mucosal secretion (S-IgA) and systemic (IgG, IgA)
immune response following intranasal vaccination with BPZE1
boost dose proceeded by Boostrix or BPZE1 prime dose.

To assess nasal mucosal secretion (S-IgA) and systemic (IgG, IgA)
immune response through 9 months after a single (eg, prime) dose
and 6 months after a 2-dose series (eg, prime + boost), where the
prime dose is BPZE1 or Boostrix, and BPZE1 (or placebo) is the
boost dose.

To assess nasal mucosal secretion (S-IgA) and systemic (IgG, IgA)
immune response following immunization with BPZE1 or Boostrix
prime dose, with or without a BPZE1 boost dose, in relation to
baseline immunity status (positive [Yes/No]) of pertussis antibodies
PT, PRN, FHA, and FIM 2/3.

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Colonization: 

To assess nasopharyngeal colonization or clearance of BPZE1 in
either a prime or prime + boost strategy, and in relationship to
vaccination strategies with Boostrix.
Safety: 

To describe (severity and clinical significance) of vaccine-related
adverse events (AEs) following a single or 2-series intranasal
vaccination (prime or prime + boost) with BPZE1 or Boostrix
prime dose with or without a BPZE1 boost dose.

To describe all serious AEs during the study.
Exploratory Objective

To examine cell-mediated (eg, B cell, CD4 T lymphocytes + T cell,
CD8T lymphocytes + T cell) responses in a subset of no more than
60 subjects using peripheral blood mononuclear cells to be
collected at baseline and 8 days post-vaccination (prime and boost).
This subset will be from the randomized cohort population of 109
CFU BPZE1 only.

To further characterize nasal mucosal secretion and serum
immunological responses across time, relative to baseline status and
relative to vaccination response, with the current assays and with
any future assays developed for BPZE1.
Primary Endpoints: 
Immunogenicity: 

Mucosal seroconversion (nasal mucosal secretion sampling):
Proportion of subjects who achieve seroconversion against at least
1 pertussis antigen (PT, FHA, PRN, FIM 2/3, or BPZE1 whole cell
extract) in nasal secretions on Day 29 or 113 (prime or prime +
boost).
Mucosal seroconversion is defined as a 2-fold increase over the
baseline value (collected during screening) or a 4-fold increase over
the minimal limit of assay detection (whenever the baseline value
falls below the limits of assay detection) for any of the
pertussis-specific antibodies (S-IgA ELISA): PT, FHA, PRN, FIM
2/3, BPZE1 whole cell extract. Seroconversion will be calculated
based on absolute titer response over baseline and by standardizing
pertussis specific ELISA responses relative to non-pertussis specific
total mucosal secretion (eg, IgA). To be further defined during
assay development and within the statistical analysis plan.

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Mucosal baseline samples will be taken at the screening visit. 
Safety: 

Solicited AEs (local, nasal/respiratory, and systemic reactogenicity
events) for 7 days following each vaccination by severity score,
duration, and peak intensity. Local reactogenicity will only be
monitored following the intramuscular (IM) vaccination.

Safety laboratory results (serum chemistry, hematology,
coagulation) by US Food and Drug Administration (FDA) toxicity
score (change from baseline or absolute toxicity score) in the safety
lead-in cohort at Day 8 following each vaccination. In the case of
no toxicity classification the score of 0 will be assigned.
Secondary Endpoints: 
Systemic Immunogenicity (serum sampling) expressed separately for 
IgG, IgA, and IgG or IgA ELISA when possible: 

Proportion of subjects who achieve seroconversion against pertussis
antigen (PT, FHA, PRN, FIM 2/3, or BPZE1 whole cell extract)
over baseline for.

At least 1 antigen on each of the Days 29, 85, 113, 169, or 254

At least 1 antigen on any of the Days 29, 85, 113, 169, or 254

At least any 1 antigen on all Days 29, 85, 113, 169, or 254
Systemic seroconversion is defined as a 2-fold increase over the 
baseline value or a 4-fold increase over the minimal limit of assay 
detection (whenever the baseline value falls below the limits of 
assay detection). Both IgG and IgA ELISA will measure antibodies 
against the following pertussis-specific antigens of PT, FHA, PRN, 
FIM 2/3, and IgG ELISA will measure antibodies against broader 
pertussis-specific antigens in BPZE1 whole cell extract. 
Serum baseline samples will be taken at Day 1 prior to vaccination. 

Proportion of subjects who achieve seroconversion (IgG ELISA
only) against BPZE1 whole cell extract over baseline:

On either Day 29 (prime) or 113 (boost)

On both Days 29 (prime) and 113 (boost).

Proportion of subjects who achieve seroconversion against the
acellular pertussis (aP) antigens PT, FHA, and PRN over baseline:

On either Day 29 (prime) or 113 (boost)

On both Days 29 (prime) or 113 (boost).

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
Proportion of subjects who achieve seroconversion against 2 or
more pertussis antigens (PT, FHA, PRN, FIM 2/3, and BPZE1
whole cell extract) over baseline:

On each of the Days 29, 85, 113, 169, or 254

On any of the Days 29, 85, 113, 169, or 254

At least the same 2 antigens on all Days 29, 85, 113, 169, and
254.

Proportion of subjects who demonstrate boosting for each pertussis
antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole cell extract)
on Day 113. Boost is defined as at least a 2-fold increase from the
pre-boost sample taken on Day 85.

The Geometric Mean Fold Rise against each pertussis antigen (PT,
FHA, PRN, FIM 2/3, and BPZE1 whole cell extract):

On Days 29, 85, 113, 169, and 254 over baseline (Day 1)

On Days 113, 169, and 254 over pre-boost (Day 85)

The maximum over baseline on either Day 29 or 85
(post-priming response)

The maximum over pre-boost (Day 85) on any of the
Days 113, 169, or 254 (post-boost response)

The maximum during the study.

The Geometric Mean Titer against each pertussis antigen (PT, FHA,
PRN, FIM 2/3, and BPZE1 whole cell extract):

On Days 29, 85, 113, 169, and 254

The maximum on Day 29 or 85 (after priming dose)

The maximum after Days 113, 169, or 254 (after boosting
dose)

The maximum during the study.
Mucosal Immunogenicity S-IgA ELISA (nasal mucosal secretion 
sampling): 

Proportion of subjects who achieve seroconversion against any
pertussis-specific antigen (PT, PRN, FHA, FIM 2/3, or BPZE1
whole cell extract) over baseline:

At least 1 antigen on each of the Days 29, 78, 113, 169, or 254

At least 1 antigen on any of the Days 29, 78, 113, 169, or 254

At least any 1 antigen on all Days 29, 78, 113, 169, and 254.

Proportion of subjects who achieve seroconversion against BPZE1
whole cell extract over baseline:

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
On either Day 29 (prime) or 113 (boost)

On both Days 29 (prime) and 113 (boost).

Proportion of subjects who achieve seroconversion against aP
antigens PT, FHA, and PRN over baseline:

On either Days 29 (prime) or 113 (boost)

On both Days 29 (prime) and 113 (boost)

Proportion of subjects who achieve seroconversion for any 2 or
more pertussis antigens (PT, PRN, FHA, or BPZE1 whole cell
extract) over baseline:

On each of Days 29, 78, 113, 169, or 254

On any of Days 29, 78, 113, 169, or 254

At least the same 2 antigens on all Days 29, 78, 113, 169, and
254

Proportion of subjects who demonstrate boosting against each
pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole cell
extract) on Day 113. Boost is defined as at least a 2-fold increase
from pre-boost sample taken at Day 78.

The Geometric Mean Fold Rise against each pertussis antigen (PT,
FHA, PRN, FIM 2/3, and BPZE1 whole cell extract):

On Days 29, 78, 113, 169, and 254 over baseline (Day 1)

On Days 113, 169, and 254 over pre-boost (Day 78)

The maximum over baseline on either Day 29 or 78
(post-priming response)

The maximum over pre-boost (Day 78) on any of the
Days 113, 169, or 254 (post-boost response)

The maximum during the study.

The Geometric Mean Titer against each pertussis antigen (PT, FHA,
PRN, FIM 2/3, and BPZE1 whole cell extract):

On Days 29, 78, 113, 169, and 254

The maximum on Days 29 or 78 (after priming dose)

The maximum after Days 113, 169, or 254 (after boosting
dose)

The maximum during the study.
Colonization: 

Proportion of subjects with positive B. pertussis by bacterial culture
of nasal sample on each day and on any of Days 92, 96, and 113.

B. pertussis colony counts on each day (Days 92, 96, and 113).

Number of subjects who remain culture positive for B. pertussis at

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Days 78 (following priming) and 254 (following boost). 
Safety: 

Unsolicited AEs (eg, treatment-emergent AEs, serious AEs, and
suspected unexpected serious adverse reactions) collected for
28 days following each vaccination by Medical Dictionary for
Regulatory Activities (MedDRA) classification and severity score.

Unsolicited AEs related to vaccination through Day 113 by
MedDRA classification and severity score.

Serious AEs through 6 months following the last vaccination (or
until resolved or stable) by MedDRA classification, relatedness, and
severity score.

Vital sign measurements with severity scoring immediately
following vaccination.
Exploratory Endpoint: 

Cell-mediated (eg, B cell, CD4 T lymphocytes + T cell, CD8 T
lymphocytes + T cell) responses (eg, cell staining, cytokine
production) following stimulation of peripheral blood mononuclear
cells collected at baseline, and 8 days post-vaccination (prime and
boost) to pertussis-specific antigens. Results expressed both as
absolute values and fold over baseline (per specific assay
characteristics).

Following the outcomes of the primary and second analyses,
additional exploratory endpoints may be tested for systemic or nasal
mucosal immunogenicity (IgG or IgA) responses at any time point
collected and not already performed in the primary or secondary
analysis sets.

The Geometric Mean Titer, expressed for serum IgG ELISA against
tetanus and diphtheria on Days 29 and 113.
Study 
Population: 
Inclusion Criteria 
Each subject must meet all the following criteria to be enrolled in this 
study: 
1. Is a male or nonpregnant female 18 to 50 years of age, inclusive, on
Day 1 (primary vaccination).
2. Is capable of understanding the written informed consent, provides
signed and witnessed written informed consent, and agrees to
comply with protocol requirements.
3. Female subjects must be nonpregnant and nonlactating and meet
1 of the following criteria:
a) Postmenopausal (defined as 12 consecutive months with no

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menses without an alternative medical cause or documented 
plasma follicle-stimulating hormone level in the postmenopausal 
range); 
b) Surgically sterile (ie, hysterectomy, bilateral tubal ligation, or
bilateral oophorectomy).
NOTE: These procedures and laboratory test results must be 
confirmed by physical examination, or by subject recall of specific 
date and hospital/facility of procedure, or by medical documentation 
of said procedure. 
c) Is of childbearing potential (defined as any female who has
experienced menarche and who is NOT permanently sterile or
postmenopausal), agrees to be heterosexually inactive from at
least 21 days prior to enrollment and through 3 months after the
boosting vaccination or agrees to consistently use any of the
following methods of contraception from at least 21 days prior
to enrollment and through 3 months after the boosting
vaccination:
i.
Condoms (male or female) with spermicide
ii.
Diaphragm with spermicide
iii.
Cervical cap with spermicide
iv.
Intrauterine device
v.
Oral or patch contraceptives
vi.
Norplant®, Depo-Provera®, or other FDA-approved
contraceptive method that is designed to protect against
pregnancy.
NOTE: Periodic abstinence (eg, calendar, ovulation, symptothermal, 
post-ovulation methods) and withdrawal are not acceptable methods 
of contraception. 
4. Has a stable health status as assessed by the investigator, as
established by physical examination, vital sign measurements, and
medical history.
5. Has access to a consistent and reliable means of telephone contact,
which may be in the home, workplace, or by personal mobile
electronic device.
6. Is able to understand and comply with planned study procedures.
7. Lives a reasonable distance from the clinical site to be able to travel
to and from the clinical site for follow-up visits and agrees to go to
the clinical site for evaluation (or provide medical record access if
evaluated elsewhere) in the event of an AE.
8. Agrees to stay in contact with the clinical site for the duration of the

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study, has no current plans to move from the study area, and 
provides updated contact information as necessary. 
Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the 
study: 
1. History of being vaccinated in the past 5 years against pertussis
(subject recall).
2. Any significant past reaction to any component of Boostrix (at the
discretion of the investigator).
3. Subject reported diagnosis of pertussis in the past 10 years (must be
laboratory confirmed or physician diagnosed from medical records).
4. Vital signs by FDA toxicity scoring >1 (may be repeated once
during the screening period to allow for inclusion and the most
recent measurement taken at baseline).
5. Chronic illness being treated actively and with evidence of recent
intervention for worsening or fluctuating symptoms (at the
discretion of the investigator).
6. The subject has a history of active cancer (malignancy) in the last
10 years (exception is subjects with adequately treated
non-melanomatous skin carcinoma, who may participate in the
study).
7. Current use of any smoking products and unwillingness to refrain
from the use of any smoking products from screening through
28 days after the boosting vaccination.
8. Use of narcotic drugs, evidenced by urine toxicology screen or a
history of drug/alcohol abuse within the past 2 years.
9. Has donated blood or suffered from blood loss of more than 450 mL
(1 unit of blood) within 60 days prior to screening or donated
plasma within 14 days prior to screening.
10. Receipt of immunoglobulin, blood-derived products, systemic
corticosteroids, or other immunosuppressant drugs within 90 days
prior to Day 1.
11. Asthma*, obstructive nasal canal, recurrent or acute sinusitis or
other chronic respiratory problems inclusive of the diagnosis of any
significant pulmonary disease. *Asthma as diagnosed with
spirometry showing reversibility of disease and must meet at least
Step 1 classification with current prescription/use of medications to
control symptoms (EPR-3 2007).
12. History of nasal surgery or Bell’s palsy.
13. Use of repeated nasal sprays, Neti pot, routine nasal washing within

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the past 1 month (more than 2 times per week). Subjects must agree 
to refrain from use of any of these modalities through Day 113.  
14. A temporary exclusion to vaccinate if acute respiratory tract
infection or rhinorrhea or temperature >100.4°F (no symptoms for
3 days prior to vaccination day). Subjects may be vaccinated if they
stay within the vaccination window (screening [30 days] or at the
time of the booster [10 days]).
NOTE: If a subject exceeds the screening window, they must be 
reconsented and screening must be reinitiated. 
15. Use of corticosteroids in the respiratory tract (eg, nasal steroids,
inhaled steroids) within 30 days prior to Day 1.
16. Receipt of a licensed vaccine within the last 30 days prior to Day 1
or planned vaccination during the active study conduct through
Day 113. In the case of seasonal influenza, vaccination should not
be withheld and is not contraindicated for subject participation.
However, vaccination should be planned outside of a 30-day pre- 
and 30-day post-vaccination window whenever possible.
17. Known hypersensitivity to any component of the study vaccines.
18. Participation in any other clinical trial for the testing of an
unlicensed product during the previous 6 months or planned during
the study conduct.
NOTE: “Testing” is intended to mean receipt an investigational product. 
Subjects in long term safety follow-up studies where vaccination has 
been completed greater than 6 months prior to this study enrollment are 
allowed. 
19. Inability to adhere to the protocol, including plans to move from the
area.
20. Personal history or family (first degree) history of congenital or
hereditary immunodeficiency.
21. Past or present infection with human immunodeficiency virus,
hepatitis B, or hepatitis C by screening test.
22. Any autoimmune or immunodeficiency disease/condition (inherited
or iatrogenic).
NOTE: Stable endocrine disorders that have a confirmed autoimmune 
etiology (eg, thyroid, pancreatic) are allowed. 
23. Any neurological disease or history of significant neurological
disorder (eg, meningitis, seizures, multiple sclerosis, vasculitis,
migraines*, Guillain-Barré syndrome [genetic/congenital or
acquired]). *Significant neurological migraine includes frequent
migraine (2 times a month or greater), migraine with aura or

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migraine with complications (status migraninosus, persist aura 
without infarction, infarction or aura triggered seizure defined by 
International Classification of Headache Disorders-3 
[ICHD-3 2018). 
24. Any medical condition that, in the opinion of the investigator, might
interfere with the evaluation of the study objectives or might affect
the safety of the individual, (eg, major depression or history of
suicidal attempt).
25. Toxicity grading >1 for screening laboratory test results for specific
kidney, hepatic, and hematologic values for all subjects and in
screening laboratory values for the safety cohort as indicated in
Table 13-2 (may be repeated once during the screening period to
allow for inclusion and the most recent measurement taken at
baseline). See Table 13-2 for specifically designated parameters.
26. Body mass index <17 kg/m2 or >40 kg/m2.
27. Frequent contact with children less than 1 year of age (parent,
childcare worker, nurse, etc.) or residence in the same household as
persons with known immunodeficiency including persons on
immunosuppressant therapy.
28. Study team member or first-degree relative of study team member.
Study Design: 
This is a multi-center, randomized, placebo-controlled, and 
observer-blinded trial with a 6-month safety follow-up after the last 
vaccination. After signing the informed consent form, subjects will be 
enrolled in the trial and screened over a window of 30 days; screening 
will include obtaining a nasal sample for mucosal pertussis immune 
status. Subjects will also be asked to provide a signed informed consent 
for the use of samples for further pertussis-specific testing or assay 
development. On Day 1, eligible subjects will be randomized to 1 of 
4 treatment arms and receive BPZE1 intranasal vaccine or formulation 
buffer for injection (placebo) (via the VaxINator™ atomization device) 
and a licensed aP comparator vaccine (ie, Boostrix) or sterile normal 
saline (placebo), given by IM injection. To maintain the blind 
throughout the trial period, placebo vaccination via intranasal and IM 
routes, using formulation buffer and normal saline, respectively will be 
included, and unblinded pharmacy staff will manage vaccine logistics, 
preparation, and (if needed) administration but will not be involved in 
study-related assessments or have subject contact for data collection 
after study vaccine administration. Approximately 300 subjects will be 
randomly assigned 2:1 for the first (prime) vaccination with 200 subjects 
assigned to BPZE1 vaccination and 100 subjects assigned to Boostrix 
(aP vaccine) vaccination. During the second (boosting) vaccination, half 

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of each of the treatment groups will be further randomly assigned to 
receive BPZE1 or placebo resulting in a 2:2:1:1 randomization scheme. 
Dosing Scheme 
Timing 
Day 1 
Day 85 
Treatment 
Arm 
Nasal Vaccination 
IM Vaccination 
Nasal Vaccination 
BPZE1 
Placeboa 
Boostrix 
Placebob 
BPZE1 
Placeboa 
A (N = 100)
X
-
-
X
X
-
B (N = 100)
X
-
-
X
-
X
C (N = 50)
-
X
X
-
X
-
D (N = 50)
-
X
X
-
-
X
Abbreviation: IM, intramuscular. 
a  Intranasal application of 2 × 0.4 mL (0.4 mL per nostril) placebo (formulation buffer). 
b  IM injection of 0.5 mL placebo (normal saline) to the deltoid region. 
As part of the screening procedures, all subjects will provide a nasal 
sample for determination of mucosal (S-IgA) pertussis antibody status, 
with this sample collected at least 6 days prior to randomization. Day 1 
vaccination (primary) will be delivered by intranasal application 
(BPZE1 or placebo) and by IM injection into the deltoid (Boostrix [aP 
vaccine] or placebo), with subjects randomized to receive 1 of the 
4 final treatment regimens. Nasal secretion sampling for mucosal 
antibody response (S-IgA ELISA) to pertussis-specific antigens will 
occur at baseline (screening) and Days 29 and 78 post-primary 
vaccination. Serum sampling for antibody response (IgG and IgA 
ELISA) will occur at baseline (Day 1, prior to primary vaccination) and 
on Days 29 and 85 (prior to boosting vaccination). Subjects will be 
tested for BPZE1 clearance (colonization) from the nasal tract via a 
standard nasal secretion sampling on Day 78. There needs to be at least 
6 days between the nasal secretion sampling, which will occur at Visit 4 
(Day 78), and the boosting intranasal vaccination. The boosting 
vaccination visit (Day 85 [+7 days]) will consist of all subjects receiving 
intranasal administration (BPZE1 or placebo) with half of the subjects 
who received BPZE1 for the primary vaccination receiving a second 
dose of BPZE1 and the other half of subjects receiving placebo 
(formulation buffer for injection). Similarly, half of the subjects 
receiving Boostrix will receive BPZE1 and half will receive placebo. 
Colonization following the boosting vaccination will be measured on 
Days 92, 96, and 113 by standard nasal secretion sampling. Any subject 
who tested positive by pertussis culture Day 113 will be retested at Day 
254 or at the time of the end-of-study visit. Chronic carriage of BPZE1 
has not been reported (ie, the majority of subjects have been clear at 
Day 29 and no subject has had positive cultures at Day 46) and is 
therefore not expected. Any subject who remains positive for pertussis at 
Day 254 will be provided a short course of azithromycin, which is 

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clinically used to eradicate B. pertussis from the nasopharynx. Should a 
subject be allergic to azithromycin, an appropriate antibiotic will be 
substituted that has effectiveness against B. pertussis. Mucosal (S-IgA 
ELISA) and serum response (IgG and IgA ELISA) to pertussis-specific 
antigens after boosting will be tested on Days 113, 169, and 254. 
The first 48 subjects randomly assigned will be designated the safety 
lead-in cohort and will be sequentially enrolled by escalating dose. The 
first 24 subjects will be randomly assigned as noted above in a ratio of 
2:1 to receive active products of either an intranasal dose of 107 CFU of 
BPZE1 or IM Boostrix. These subjects will be followed through Day 8 
with safety laboratory tests, reactogenicity, and AE assessments with 
daily review by the medical monitor for activation of any halting rule. 
Following accumulation of all safety data through Day 8 
post-vaccination and without a safety pause being triggered, the 
24 additional subjects will be randomly assigned 2:1 to receive active 
products of either an intranasal dose of 109 CFU of BPZE1 or IM 
Boostrix. To maintain the blind for intranasal and IM administered 
products, all subjects will also receive appropriate placebo vaccinations. 
All safety lead-in subjects will have safety laboratory testing at baseline 
(screening), and on Days 8, 85 (prior to vaccination), and 92. Subjects 
will continue with the booster using the same intranasal dose level 
(107 CFU or 109 CFU) assigned for the first dose. The medical monitor 
has the authority to request a review by the Safety Monitoring 
Committee should a halting rule be initiated or there are any other safety 
concerns. The Safety Monitoring Committee will convene after the 
subjects in the entire safety lead-in cohort (both dose levels) have 
completed Day 8 (Visit 2) and will review all safety data through Day 8 
(reactogenicity and safety laboratory results) and any AEs which have 
occurred since study initiation. The Safety Monitoring Committee will 
be authorized to allow the remainder of the subjects to be randomly 
assigned. The randomization scheme for the safety lead-in will follow 
the same scheme as the full cohort for second vaccination such that half 
the BPZE1 and half the Boostrix vaccinated subjects will receive 
intranasal BPZE1 vaccination on Day 85 and the other half will receive 
placebo. 
 
 
 
 

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Table 1 
Dosing and Safety Lead-In Cohort 
BPZE
1 Dose 
BPZE1 
Boostrix 
Trigger to 
advance 
Review 
Process 
Advancing 
to 
107 
N = 16 
N = 8 
Day 8 safety on 
107 dosing 
cohort 
Pause rules; 
daily medical 
monitor 
reviews
109 safety 
lead-in 
109 
N = 16 
N = 8 
Day 8 safety on 
full safety lead-
in cohort; all 
adverse events
Safety 
Monitoring 
Committee 
review
Full cohort 
All subjects will be monitored for 60 minutes after vaccine 
administration on Days 1 and 85. After the subjects have been monitored 
for 60 minutes post-vaccination, vital signs will be collected and a 
post-vaccination examination for reactogenicity (local, nasal/respiratory, 
and systemic) with toxicity grade will be completed. 
Subjects will receive a daily subject diary on Days 1 and 85 after each 
vaccination. All subjects will record reactogenicity in the daily subject 
diary starting the same day of the primary (Day 1) and boosting 
(Day 85) vaccinations and for 7 additional days (not counting 
vaccination day). For primary vaccination site-specific local (arm), 
nasal/respiratory, general systemic reactogenicity reactions, and other 
unsolicited symptoms/complaints (including start and stop dates) will be 
recorded and standard toxicity grading will be applied by the 
investigator at the subsequent visit (Visit 2). For the boost vaccination, 
nasal/respiratory, general systemic reactogenicity reactions, and other 
unsolicited symptoms/complaints (including start and stop dates) will be 
recorded and standard toxicity grading will be applied by the 
investigator at the subsequent visit (Visit 6). The clinical staff will 
review the information from the subject diaries with the subjects on 
Days 8 and 92 (Visits 2 and 6). Should any reactogenicity event extend 
beyond 7 days post-vaccination and be clinically significant by toxicity 
grade 1 or greater, then it will be entered as an AE with the same start 
date as the reactogenicity event and followed to resolution. 
All AEs will be monitored through 28 days after the primary and 
boosting vaccinations. Unsolicited AEs related to vaccination will be 
monitored through Day 113 (unless resolved or felt to be stable at an 
earlier date). Serious AEs and AEs of special interest (if newly 
identified) will be monitored to the end of the study. The primary 
database lock will occur at Day 113, and all data collected through 
Day 113 will be included in the clinical study report and submitted to 
regulatory authorities. A subsequent longer-term safety follow-up, 
including longer term persistence of immune responses, will occur 

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through Day 254. These data will be provided, following a second 
database lock, in an addendum to the clinical study report. Subjects will 
return to the clinical site on Day 254 (±15 days) for end-of-study 
procedures. 
A subset of no more than 60 subjects (randomly assigned to the 109 CFU 
dose) will opt in to provide blood samples for peripheral blood 
mononuclear cell harvesting on Days 1, 8, and 92. 
Estimated 
Study Duration: 
Study duration is approximately 15 months; subject participation 
duration is approximately 10 months. 
Immunogenicity 
Assessments: 
Immune measurements (ELISA) will be conducted on serum (IgG and 
IgA) and nasal secretion (S-IgA) for the common pertussis antigens of 
PT, FHA, PRN, FIM 2/3 and on serum (IgG) and nasal secretions 
(S-IgA) for BPZE1 whole cell extract. Testing of additional antigens 
specific to B. pertussis may be performed at a later date as BPZE1 
induces broader immunity more similar to whole cell pertussis and does 
not contain the purified antigen levels of PT, FHA, and PRN found in 
Boostrix. Subjects will be asked to provide a signed informed consent 
for the use of samples for further pertussis-specific testing or assay 
development. Aliquots of collected samples from this study may be 
retained for additional testing of antigens specific to B. pertussis for a 
maximum of 10 years (starting from the date at which the last subject 
had the last study visit), unless local rules, regulations, or guidelines 
require different timeframes or different procedures, in accord with 
subject consent. Testing for colonization using B. pertussis culture 
following the primary vaccination and post-boost will also occur. 
Colony counts as well as culture positivity (yes/no) will be included in 
the colonization assessments post-boosting.  
Safety 
Assessments: 
Safety assessments will include the following: 
 Vital sign measurements (oral temperature, pulse rate, and blood 
pressure) 
 Physical examination 
 Clinical safety laboratory tests (hematology, chemistry, coagulation 
at baseline and in the safety lead-in cohort following vaccination) 
and urine pregnancy test in women of childbearing potential 
 Solicited local, nasal/respiratory, and systemic reactogenicity 
symptoms during the 7 days after each vaccination (Days 1 
through 8 and 85 through 92). Local reactogenicity will only be 
monitored following the IM vaccination. 
 Adverse events through 28 days after the primary and boosting 
vaccination 

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 Adverse events associated with vaccination through Day 113 (unless 
resolved or stable at an earlier date) 
 Serious AEs and any AEs of special interest from the time of the 
primary vaccination through the last visit 
Study Drug, 
Dosage, and 
Route of 
Administration: 
Live attenuated B. pertussis BPZE1 vaccine, 2 × 0.4 mL (0.4 mL per 
nostril containing half the dose 5 × 108 bacteria to give a total dose of 
109 CFU) and a dilution of the same stock to achieve 107 CFU in the 
same total volume for the first cohort lead-in (n = 24 subjects). See the 
pharmacy manual for specific dilution requirements. 
Boostrix IM injection, 0.5 mL to the deltoid region (aP vaccine, 
manufactured by GlaxoSmithKline) 
Placebo (BPZE1 formulation buffer for injection) 2 × 0.4 mL (0.4 mL 
per nostril)  
Placebo IM injections of 0.5 mL sterile normal saline to the deltoid 
region 
Sample Size: 
The sample size is based on clinical considerations but not a statistical 
power analysis as the study does not test any formal null hypothesis. A 
total of 300 subjects will be globally assigned at 2:2:1:1 allocation ratio 
and receive BPZE1 intranasal administration with placebo IM or 
Boostrix IM with placebo intranasal administration on Day 1 and then 
BPZE1 or placebo intranasal administration on Day 85. 
Statistical 
Methods: 
The objectives of this study are to assess the nasal mucosal and systemic 
immunogenicity, reactogenicity, and general safety parameters of 
lyophilized BPZE1 at 107 and 109 CFU administered intranasally via 
VaxINator atomization device to either a single (prime) or 2 dose (prime 
+ boost) schedule. Secondly, to compare responses to a licensed aP 
comparator vaccine (ie, Boostrix) given by IM injection, in healthy 
volunteers 18 to 50 years of age, as well as to assess safety and immune 
response to BPZE1 boost after Boostrix priming. 
Statistical analysis will be performed using SAS software Version 9.3 or 
later. Continuous variables will be summarized using the mean, 2-sided 
95% CI of the mean, SD, median, minimum value, and maximum value. 
Categorical variables will be summarized using frequency counts and 
percentages, as well as 2-sided 95% CI for proportions computed using 
Clopper-Pearson method. Where applicable, data analyses will be 
conducted for the prime period (prior to boosting) and boost period (at 
or after boosting). 
Version and 
Date of 
Protocol: 
Version 6.0; 20 November 2019 

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List of Abbreviations 
Abbreviation 
Definition 
AE 
adverse event 
aP 
acellular pertussis 
CDROM 
compact disc read-only memory 
CFR 
Code of Federal Regulations 
CFU 
colony-forming units 
CRO 
contract research organization 
CSR 
clinical study report 
DNT 
dermonecrotic toxin 
eCRF 
electronic case report form 
ELISA 
enzyme-linked immunosorbent assay 
FDA 
US Food and Drug Administration 
FHA 
filamentous hemagglutinin 
FIM 
fimbriae 
GCP 
Good Clinical Practice 
GMFR 
Geometric Mean Fold Rise 
GMT 
Geometric Mean Titer 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IgA 
immunoglobulin A 
IgG 
immunoglobulin G 
IM 
intramuscular 
IRB 
institutional review board 
MedDRA 
Medical Dictionary for Regulatory Activities 
PBMC 
peripheral blood mononuclear cell 
PRN 
pertactin 
PT 
pertussis toxin 
S-IgA 
secretory immunoglobulin A 
SAE 
serious adverse event 
SMC 
Safety Monitoring Committee 
SUSAR 
suspected unexpected serious adverse reaction 

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Abbreviation 
Definition 
TCT 
tracheal cytotoxin 
WFI 
water for injection 

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1 
Introduction 
1.1 
Background Information 
Currently registered acellular pertussis (aP) vaccines protect against respiratory disease but 
not against colonizing Bordetella pertussis infection and transmission. B. pertussis is a 
gram-negative bacterium and a causative agent of pertussis, more commonly known as 
whooping cough. In a nonhuman primate model, convalescence from a natural B. pertussis 
infection protected against colonizing infection and transmission caused by a subsequent 
virulent B. pertussis challenge (Warfel et al 2014), ie, a natural infection confers sterilizing 
immunity. Similarly, a single intranasal administration of the highly attenuated live B. 
pertussis vaccine BPZE1 has demonstrated in the nonhuman primate model the ability to 
reduce the bacterial burden of a substantial B. pertussis challenge by more than 99.8% 
compared to prior studies challenging baboons immunized with 3 doses of aP vaccine (Locht 
et al 2017). ILiAD has licensed BPZE1 from the Institut Pasteur de Lille and Inserm with 
worldwide rights and the company is conducting further clinical and regulatory development.  
Despite the dramatic decline in whooping cough cases and deaths in industrialized nations 
during the 20th century due to public health vaccine initiatives, recent decades have 
witnessed a sharp increase in cases and it is generally agreed that there is a critical need for a 
new and more effective vaccine targeting B. pertussis. In 2014, it was estimated there were 
24.1 million pertussis cases and 160,700 deaths from pertussis in children younger than 
5 years of age, with 53% of the estimated deaths being in infants younger than 1 year 
(Yeung et al 2017). Infants are not fully protected and require a series of vaccinations against 
pertussis. With the current acellular vaccines being ineffective against colonization (and 
therefore transmission) there is little to any herd immunity that can develop, leaving infants 
at risk for acquiring pertussis from close contacts. As a potential solution to this problem, the 
BPZE1 vaccine has been developed to be given as a single intranasal administration. Unlike 
existing vaccines, BPZE1 has the potential to prevent transmission of B. pertussis from 
siblings and adults to neonatal infants. While ultimately intended for vaccinating neonatal 
infants, a nearer term solution is to immunize adults and adolescents with BPZE1 to prevent 
transmission of B. pertussis to vulnerable infants. 
BPZE1 was engineered by genetically altering or removing 3 B. pertussis toxins: pertussis 
toxin (PT), tracheal cytotoxin (TCT), and dermonecrotic toxin (DNT). Genetic stability of 

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liquid BPZE1 formulation was demonstrated in vitro and in vivo. The safety of liquid BPZE1 
has been assessed in immunocompetent and immunosuppressed animals (Feunou et al 2008; 
Meilcarek et al 2006; Meilcarek et al 2010; Skerry et al 2009). These results contributed to 
downgrading BPZE1 from a biosafety level 2 organism to biosafety level 1 in France and 
other European countries. Good Laboratory Practice-compliant toxicological studies have 
confirmed the safety of BPZE1 in 2 animal models (mouse and rabbit) (ILiAD 
Biotechnologies 2017).  
BPZE1 in a liquid formulation has been studied at various doses from 103 colony-forming 
units (CFU) to 109 CFU in 2 Phase 1 clinical studies in Sweden with no vaccine-related 
serious adverse events (SAEs) and comparable general adverse events (AE) to placebo 
controls. A total of 78 healthy subjects have now received intranasally administered BPZE1 
in a liquid formulation. The most recent Phase 1b study has demonstrated the ability for a 
0.4 mL (400 µL) per nostril dose of 107, 108, and 109 CFU BPZE1 to achieve transient 
nasopharyngeal colonization in >80% of subjects. Furthermore, 92% of the subjects in the 
107 and 108 CFU/dose groups and 100% of the 109 CFU group had a positive serological 
response (immunoglobulin G [IgG] or immunoglobulin A [IgA]) to any of the 4 B. pertussis 
antigens tested, and 100% of the 109 CFU subjects had a positive serological response (IgG 
or IgA) to 2 or more of the antigens tested. The 109 CFU dosage appears to be the most 
promising to elicit the needed immune response in the majority of adults. None of the 
placebo subjects had a positive serological response (IgG or IgA) to 2 or more antigens tested 
(ILiAD Biotechnologies 2017). 
A separately ongoing Phase 2a clinical study is comparing 2 doses (107 and 109 CFU) of the 
lyophilized formulation of BPZE1, delivered by the VaxINator™ conical-shape atomization 
device connected to a 1-mL syringe. The study will assess the new lyophilized formulation of 
the BPZE1 vaccine to be evaluated in US adults and will provide an opportunity to 
characterize the immunological response of 2 different dosages delivered by nasal 
immunization. The main advantage of the lyophilized BPZE1 formulation is long-term 
stability and storage at refrigeration temperature instead of storage at a very low freezing 
temperature. Mouse potency and adherence assays have demonstrated similar results for the 
lyophilized and liquid formulations. Prior to vaccination, the lyophilized product will be 
reconstituted, and vaccine will be delivered as a liquid formulation using a nasal applicator to 
improve consistent delivery.  

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For this Phase 2b study, the BPZE1 experimental vaccine will be supplied in a lyophilized 
vial for reconstitution prior to intranasal administration via the VaxINator atomization device. 
Two lyophilized BPZE1 experimental vaccine doses, 107 CFU and 109 CFU, will be 
evaluated in the safety lead-in cohort of the 2b study with subjects continuing with the same 
intranasal dose level through the booster (107 CFU or 109 CFU). The dose targeted for the 
remainder of the subjects in the Phase 2b study will be 109 CFU unless a safety concern 
arises and the Safety Monitoring Committee (SMC) recommends proceeding with the 107 
CFU dose only. The 109 CFU is described throughout this protocol as the default dose level 
for the full cohort for purposes of consistent presentation. 
The vaccine will be shipped from ILiAD’s European contract manufacturing organization to 
the contract research organization’s (CRO’s) repository and distribution center and should be 
stored at –20°C or below prior to shipping to the clinical sites, where the vaccine can be 
stored at –10°C or below, and is expected to have a 1-year shelf-life that can be extended 
with periodic ongoing retests conducted every 4 months by ILiAD’s European contract 
manufacturing organization. The lyophilized BPZE1 is reconstituted in 1 mL of sterile water 
for injection (WFI), with 0.8 mL per dose removed from the vial for use. The reconstituted 
vaccine is recommended to remain at room temperature for 60 minutes or less prior to 
vaccination and therefore attention to the timing of pharmacy reconstitution and vaccination 
of individuals will be critical. After correct dilution (to obtain 107 or 109 CFU per the 
pharmacy manual) the VaxINator will be attached to the syringe filled with reconstituted 
BPZE1, with half of the dose (0.4 mL) administered into each nostril. For the placebo control 
nasal vaccination, the formulation buffer used for BPZE will be similarly diluted with sterile 
water (WFI) and used with the vaccinator at the same dose (0.4 mL per nostril). Only clinical 
staff trained on use of the VaxINator will be allowed to provide intranasal vaccinations and 
the study blind will be maintained by use of an opaque syringe (or other similar blinding 
technique). Unblinded study drug personnel will deliver the intramuscular (IM) vaccination 
unless the syringes can be masked to ensure no unblinding will occur for clinical staff 
involved in subject assessments.  
1.2 
Rationale 
The availability of a cost-effective pertussis vaccine that provides improved efficacy and 
prolonged protection with the potential to reduce or eliminate transmission would present a 
breakthrough in the prevention of colonizing pertussis infections. This novel approach may 

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not only protect BPZE1-vaccinated individuals from B. pertussis infection but may also 
reduce the B. pertussis reservoir in the adult population. The ability to prevent colonization 
by wild type B. pertussis that enable transmission may facilitate substantial reduction in the 
incidence of pertussis in infants. 
The intranasally administered BPZE1 vaccine provides an opportunity to generate a locally 
effective nasal mucosal antibody response at the site of potential exposure, and thereby 
mimics the route of entry of the wild type pathogen and results in a broader immune response 
(type 1 T helper cells, type 2 T helper cells, and nasal mucosal immune responses) (Wearing 
and Rohani 2009). The study population, healthy adults, has been chosen to maximize the 
quality of immunogenicity data while minimizing risk and potential safety signals.  
We hypothesize that the BPZE1 vaccine will be safe and induce nasal mucosal immunity 
beyond that observed with standard vaccination with Boostrix™ and that BPZE1 will also 
induce systemic immunity. Immunity will be measured in enzyme-linked immunosorbent 
assays (ELISA) specific for PT, filamentous hemagglutinin (FHA), pertactin (PRN), and 
fimbriae (FIM) 2/3, and a broader pertussis ELISA developed with BPZE1 whole cell 
extract. In addition, we hypothesize that a priming dose of intranasal BPZE1 vaccine will 
result in fewer subjects colonized (eg, lower colony counts) following a boosting dose of 
BPZE1, whereas a priming dose of Boostrix will not reduce colonization following a 
boosting dose of BPZE1, ie, Boostrix will generate less nasal mucosal immunity to prevent 
colonization by the BPZE1 live attenuated B. pertussis strain. Lastly, given that the majority 
of the population has received pertussis vaccination on multiple occasions, this study will 
assess the safety and immune response of BPZE1 as booster delivered after a prime dose of 
Boostrix in an adult population. 
1.3 
Potential Risks and Benefits 
1.3.1 
Potential Risks 
Potential risks include risks of study participation (in general), specific risks to study 
subjects, and theoretic risks to the environment through the introduction of an attenuated 
B. pertussis strain into human hosts. 

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1.3.2 
Risks of Study Participation 
The risks of study participation include exposure to the study product, maintenance of 
confidentiality, and side effects of phlebotomy. All risks will be minimized to every extent 
possible.  
1.3.3 
BPZE1 Risks to Study Subjects 
The risks of BPZE1 administration are expected to be minimal and clinically manageable. 
B. pertussis colonization is strictly limited to respiratory epithelium without dissemination of 
the bacteria outside the respiratory tract, which also excludes systemic bacteremia of the 
BPZE1 strain.  
B. pertussis is spread mainly by aerosol formed by coughing of infected persons. The 
coughing is induced by the TCT, which is more than 95% reduced in BPZE1. The BPZE1 
strain is not expected to induce coughing, therefore transmission is highly unlikely. 
Bordetella species have fastidious growth requirements and have limited survival time 
outside the human body.  
B. pertussis has not been shown to be allergenic in any preclinical or clinical studies to date, 
nor to have any of the excipients in the lyophilized formulation. BPZE1 has been shown to 
protect against airway inflammation induced by allergens or viral infections in a murine 
model (Althouse and Scarpino 2015). BPZE1 has also been shown to protect against wild 
type B. pertussis infection 3 hours after immunization in a murine model (Mielcarek et al 
2006). However, there remains a theoretical risk of allergic reaction, as is present with any 
vaccine product. 
BPZE1 vaccine or the placebo will be administered nasally via the VaxINator atomization 
device attached to a syringe to healthy adult volunteers under strictly controlled conditions. 
The VaxINator atomizes the liquid vaccine as it exits the syringe. There are no additional 
risks to study subjects based on the use of the VaxINator device.  
To minimize the risk of transmission, the subjects will stay at the study center for at least 
60 minutes after administration on Days 1 and 85. In addition, subjects with frequent contact 
with children less than 1 year of age (parent, childcare worker, nurse, etc.) or subjects who 
live in the same household as individuals with known immunodeficiency or individuals on 

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immunosuppressant therapy will be excluded from participation in the study. The attenuated 
BPZE1 bacteria colonize the upper respiratory tract similarly to wild-type B. pertussis. 
Colonization of the live organism will be assessed from nasopharyngeal sampling performed 
on Days 78 (after a mucosal pertussis nasal antibody collection is completed), 92, 96, and 
113 (after a mucosal pertussis nasal antibody collection is completed). Any subject who 
tested positive by pertussis culture at Day 113 will also have a nasal collection taken for 
pertussis culture on Day 254. Any subject who remains positive at Day 254 will be provided 
a short course of azithromycin, which is clinically used to eradicate B. pertussis from the 
nasopharynx. Should a subject be allergic to azithromycin, an appropriate antibiotic will be 
substituted that has effectiveness against B. pertussis. 
Furthermore, in animal studies, when female mice were vaccinated with BPZE1 shortly 
before mating, no negative effect on either the pregnancy or their offspring was observed. 
The offspring were protected against B. pertussis challenge (Feunou et al 2016). 
Previous clinical trials completed in subjects who received 107, 108, or 109 CFU/subject 
reported AEs. None of the subjects had spasmodic cough of grade 2 or more or any other AE 
related or possibly related to vaccination of grade 3 or higher. Among 54 subjects 
(42 vaccinated with an active vaccine and 12 with placebo), the most frequently solicited 
AEs during the first 28 days were sneezing (n = 61 in 29 subjects), fatigue (n = 51 in 
28 subjects), headache (n = 42 in 27 subjects), rhinorrhea (n = 41 in 26 subjects), and nasal 
congestion (n = 39 in 25 subjects). The reported symptoms were mostly mild or moderate. 
There were no consistent signals for differences in AE occurrence between placebo and the 
different dose groups. 
In summary, the risk assessment for this study shows a very low potential risk for the study 
subjects and impact associated with administering BPZE1.  
1.3.4 
Risks to the Environment or Potential for Interaction With 
Wild-Type B. Pertussis Strains 
To avoid accidental exposure actions should be taken to minimize generation of aerosols, 
since the bacterium is strictly a respiratory tract organism. The subjects and clinical staff 
members should wear eye-protective glasses and masks during the vaccination. Persons 
handling the BPZE1 bacteria should wear gloves and must wash their hands with a suitable 

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disinfecting soap before touching their skin and eyes. Effective antibiotic treatment with 
azithromycin (or an appropriate antibiotic if the subject is allergic to azithromycin) should be 
given in case of accidental transmission to other humans. 
The attenuated strain of B. pertussis (BPZE1) was engineered by genetically altering or 
removing 3 B. pertussis toxins: PT, TCT, and DNT. The genetic modifications (replacement 
of the ampG gene, deletion of the DNT, and the mutations of the PT) are not expected to alter 
the host range of B. pertussis BPZE1 compared to the wild-type B. pertussis.  
Due to the robust preclinical safety data, BPZE1 has been classified as a Biosafety 
Level 1 organism by French authorities Republique Francaise Ministere De L’enseignement 
Superieur Et De La Recherche (French Ministry of Higher Education and Research). 
Germany, Belgium, Spain, and Sweden have accepted the French Authority’s Biosafety 
Level 1 rating for the purpose of manufacturing and clinical studies.  
The genetic modifications in BPZE1 strongly increase the in vivo and in vitro safety: 
 The double nucleotide mutation in the substrate binding and the active site of the PT 
results in a strong reduction of the enzyme activity. 
 The replacement of the B. pertussis ampG gene by the Escherichia coli ampG gene 
results in an over 95% reduction in release of the TCT in the medium. 
 The DNT is not expressed in the BPZE1 strain. 
 BPZE1 is not invasive and has no selective advantage in the environment. The 
potential for exchange of genetic material is virtually nonexistent since B. pertussis 
does not harbor plasmids or conjugative transposons. In addition, B. pertussis 
Tohama I (origin of BPZE1) does not harbor intact prophage genomes and is 
therefore incapable of producing functional phage particles. 
Chronic carriage of B. pertussis has not been reported and is therefore not expected. No 
cross-contamination between the subjects was observed in the previous Phase 1 clinical trials 
of BPZE1, nor was any risk to the family members of study subjects observed. In case of 
transmission to other humans, accidentally exposed, an efficient treatment against 
B. pertussis is commercially available and is based on administering erythromycin. BPZE1 
has been shown to be sensitive to erythromycin. 

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In summary, the preliminary risk assessment for this study suggests there is an extremely low 
risk for potential environmental impact associated with administering the BPZE1 to study 
subjects. 
1.3.5 
Boostrix Risks to Study Subjects 
The risks of Boostrix administration are expected to be minimal and clinically manageable. 
Local adverse reactions include pain, redness, swelling, and injected arm circumference 
increase. General adverse reactions include headache, fatigue, gastrointestinal symptoms, and 
fever. 
The tip caps of the prefilled syringes contain natural rubber latex which may cause allergic 
reactions.  
If Guillain-Barré syndrome occurred within 6 weeks of receipt of a prior vaccine containing 
tetanus toxoid, the risk of Guillain-Barré syndrome may be increased following a subsequent 
dose of tetanus toxoid-containing vaccine, including Boostrix.  
Syncope can occur in association with administration of injectable vaccines, including 
Boostrix. Syncope can be accompanied by transient neurological signs such as visual 
disturbance, paresthesia, and tonic-clonic limb movements. Procedures for administration 
should be in place to avoid falling injury and to restore cerebral perfusion following syncope.  
Progressive or unstable neurologic conditions (eg, cerebrovascular events and acute 
encephalopathic conditions) are reasons to defer vaccination with a pertussis-containing vaccine, 
including Boostrix. It is not known whether administration of Boostrix to subjects with an 
unstable or progressive neurologic disorder might hasten manifestations of the disorder or affect 
the prognosis. Administration of Boostrix to subjects with an unstable or progressive neurologic 
disorder may result in diagnostic confusion between manifestations of the underlying illness and 
possible adverse effects of vaccination.  
Persons who experienced an Arthus-type hypersensitivity reaction following a prior dose of a 
tetanus toxoid-containing vaccine usually have a high serum tetanus antitoxin level and should 
not receive Boostrix or other tetanus toxoid-containing vaccines unless at least 10 years have 
elapsed since the last dose of tetanus toxoid-containing vaccine.  

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As with any vaccine, if administered to immunosuppressed individuals, including individuals 
receiving immunosuppressive therapy, the expected immune response may not be obtained.  
Prior to administration, the healthcare provider should review the immunization history for 
possible vaccine sensitivity and previous vaccination-related adverse reactions to allow an 
assessment of benefits and risks. Epinephrine and other appropriate agents used for the control of 
immediate allergic reactions must be immediately available should an acute anaphylactic reaction 
occur.  
1.3.6 
Known Potential Benefits 
The benefits of the study lie primarily in the opportunities to science and humanity. No direct 
personal benefit from participation in the study can be guaranteed, as the vaccine may or may 
not confer protection in humans.  

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2 
Study Objectives and Endpoints 
2.1 
Primary Objectives 
2.1.1 
Primary Immunogenicity Objective 
 To assess nasal mucosal secretion immune response (secretory Ig A [S-IgA]) 
following intranasal vaccination with BPZE1 (109 CFU) when used as a single (eg, 
prime) or 2-dose (eg, prime + boost) series. 
2.1.2 
Primary Safety Objective 
 To assess reactogenicity (all) and specific safety laboratory parameters (safety lead-in 
cohort only) following intranasal vaccination with BPZE1 either 107 CFU (safety 
lead-in cohort only) or 109 CFU (safety lead-in cohort and full cohort), in healthy 
adults. 
2.2 
Secondary Objectives 
2.2.1 
Secondary Immunogenicity Objectives 
 To assess the systemic immune response (IgG, IgA) following intranasal vaccination 
with BPZE1 when used as a single (eg, prime) or 2-dose (eg, prime + boost) series. 
 To assess nasal mucosal secretion (S-IgA) and systemic (IgG, IgA) immune response 
following intranasal vaccination with BPZE1 boost dose proceeded by Boostrix or 
BPZE1 prime dose. 
 To assess nasal mucosal secretion (S-IgA) and systemic (IgG, IgA) immune response 
through 9 months after a single (eg, prime) dose and 6 months after a 2-dose series 
(eg, prime + boost), where the prime dose is BPZE1 or Boostrix, and BPZE1 (or 
placebo) is the boost dose. 
 To assess nasal mucosal secretion (S-IgA) and systemic (IgG, IgA) immune response 
following immunization with BPZE1 or Boostrix prime dose, with or without a 
BPZE1 boost dose, in relation to baseline immunity status (positive [Yes/No]) of 
pertussis antibodies PT, PRN, FHA, and FIM 2/3. 

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2.2.2 
Secondary Colonization Objectives 
 To assess nasopharyngeal colonization or clearance of BPZE1 in either a prime or 
prime + boost strategy, and in relationship to vaccination strategies with Boostrix. 
2.2.3 
Secondary Safety Objectives 
 To describe (severity and clinical significance) of vaccine-related AEs following a 
single or 2-series intranasal vaccination (prime or prime + boost) with BPZE1 or 
Boostrix prime dose with or without a BPZE1 boost dose. 
 To describe all SAEs during the study. 
2.3 
Exploratory Objective 
 To examine cell-mediated (eg, B cell, CD4 T lymphocytes + T cell, CD8 
T lymphocytes + T cell) responses in a subset of no more than 60 subjects using 
peripheral blood mononuclear cells (PBMCs) to be collected at baseline and 8 days 
post-vaccination (prime and boost). This subset will be from the randomized cohort 
population of 109 CFU BPZE1 only. 
 To further characterize nasal mucosal secretion and serum immunological responses 
across time, relative to baseline status and relative to vaccination response, with the 
current assays and with any future assays developed for BPZE1.  
2.4 
Primary Endpoints 
2.4.1 
Primary Immunogenicity Endpoints 
The primary immunogenicity endpoints of this study are: 
 Mucosal seroconversion (nasal mucosal secretion sampling): Proportion of 
subjects who achieve seroconversion against at least 1 pertussis antigen (PT, FHA, 
PRN, FIM 2/3, or BPZE1 whole cell extract) in nasal secretions on Day 29 or 113 
(prime or prime + boost). 
Mucosal seroconversion is defined as a 2-fold increase over the baseline value 
(collected during screening) or a 4-fold increase over the minimal limit of assay 
detection (whenever the baseline value falls below the limits of assay detection) for 
any of the pertussis-specific antibodies (S-IgA ELISA): PT, FHA, PRN, FIM 2/3, or 

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BPZE1 whole cell extract. Seroconversion will be calculated based on absolute titer 
response over baseline and by standardizing pertussis-specific ELISA responses 
relative to non-pertussis-specific total nasal mucosal secretion (eg, IgA). To be further 
defined during assay development and within the statistical analysis plan. 
Mucosal baseline samples will be taken at the screening visit. 
2.4.2 
Primary Safety Endpoints 
The primary safety endpoints of this study are: 
 Solicited AEs (local, nasal/respiratory, and systemic reactogenicity events) for 7 days 
following each vaccination by severity score, duration, and peak intensity. Local 
reactogenicity will only be monitored following the IM vaccination. 
 Safety laboratory results (serum chemistry, hematology, coagulation) by US Food and 
Drug Administration (FDA) toxicity score (change from baseline or absolute toxicity 
score) in the safety lead-in cohort at Day 8 following each vaccination. In the case of 
no toxicity classification, the score of 0 will be assigned. 
2.5 
Secondary Endpoints 
2.5.1 
Secondary Systemic Immunogenicity Endpoints 
The secondary systemic immunogenicity (serum sampling [expressed separately for IgG, 
IgA, and IgG or IgA ELISA when possible]) endpoints of this study are: 
 Proportion of subjects who achieve seroconversion against pertussis antigen (PT, FHA, 
PRN, FIM 2/3, or BPZE1 whole cell extract) over baseline for: 
 At least 1 antigen on each of the Days 29, 85, 113, 169, or 254 
 At least 1 antigen on any of the Days 29, 85, 113, 169, or 254 
 At least any 1 antigen on all Days 29, 85, 113, 169, or 254 
Systemic seroconversion is defined as a 2-fold increase over the baseline value or a 
4-fold increase over the minimal limit of assay detection (whenever the baseline value 
falls below the limits of assay detection). Both IgG and IgA ELISA will measure 
antibodies against the following pertussis-specific antigens of PT, FHA, PRN, and FIM 

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2/3, and IgG ELISA will measure antibodies against broader pertussis-specific antigens 
in BPZE1 whole cell extract. 
Serum baseline samples will be taken at Day 1 prior to vaccination. 
 Proportion of subjects who achieve seroconversion (IgG ELISA only) against BPZE1 
whole cell extract over baseline: 
 On either Day 29 (prime) or 113 (boost) 
 On both Days 29 (prime) and 113 (boost). 
 Proportion of subjects who achieve seroconversion against the aP antigens PT, FHA, and 
PRN over baseline: 
 On either Day 29 (prime) or 113 (boost) 
 On both Days 29 (prime) or 113 (boost). 
 Proportion of subjects who achieve seroconversion against 2 or more pertussis antigens 
(PT, FHA, PRN, FIM 2/3, and BPZE1 whole cell extract) over baseline: 
 On each of the Days 29, 85, 113, 169, or 254 
 On any of the Days 29, 85, 113, 169, or 254 
 At least the same 2 antigens on all Days 29, 85, 113, 169, and 254. 
 Proportion of subjects who demonstrate boosting for each pertussis antigen (PT, FHA, 
PRN, FIM 2/3, and BPZE1 whole cell extract) on Day 113. Boost is defined as at least a 
2-fold increase from the pre-boost sample taken on Day 85. 
 The Geometric Mean Fold rise (GMFR) against each pertussis antigen (PT, FHA, PRN, 
FIM 2/3, and BPZE1 whole cell extract): 
 On Days 29, 85, 113, 169, and 254 over baseline (Day 1) 
 On Days 113, 169, and 254 over pre-boost (Day 85) 
 The maximum over baseline on either Day 29 or 85 (post-priming response) 
 The maximum over pre-boost (Day 85) on any of the Days 113, 169, or 254 
(post-boost response) 

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 The maximum during the study. 
 The Geometric Mean Titer (GMT) against each pertussis antigen (PT, FHA, PRN, FIM 
2/3, and BPZE1 whole cell extract): 
 On Days 29, 85, 113, 169, and 254 
 The maximum on Day 29 or 85 (after priming dose) 
 The maximum after Days 113, 169, or 254 (after boosting dose) 
 The maximum during the study. 
2.5.2 
Secondary Mucosal Immunogenicity Endpoints 
The secondary mucosal immunogenicity S-IgA ELISA endpoints (nasal mucosal secretion 
sampling) of this study are: 
 Proportion of subjects who achieve seroconversion against any pertussis-specific antigen 
(PT, PRN, FHA, FIM 2/3, or BPZE1 whole cell extract) over baseline: 
 At least 1 antigen on each of the Days 29, 78, 113, 169, or 254 
 At least 1 antigen on any of the Days 29, 78, 113, 169, or 254 
 At least any 1 antigen on all Days 29, 78, 113, 169, and 254. 
 Proportion of subjects who achieve seroconversion against BPZE1 whole cell extract 
over baseline: 
 On either Day 29 (prime) or 113 (boost) 
 On both Days 29 (prime) and 113 (boost). 
 Proportion of subjects who achieve seroconversion against aP antigens PT, FHA, and 
PRN over baseline: 
 On either Days 29 (prime) or 113 (boost) 
 On both Days 29 (prime) and 113 (boost). 
 Proportion of subjects who achieve seroconversion for any 2 or more pertussis antigens 
(PT, PRN, FHA, or BPZE1 whole cell extract) over baseline: 
 On each of Days 29, 78, 113, 169, or 254 

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 On any of Days 29, 78, 113, 169 or 254 
 At least the same 2 antigens on all Days 29, 78, 113, 169, and 254. 
 Proportion of subjects who demonstrate boosting against each pertussis antigen (PT, 
FHA, PRN, FIM 2/3, and BPZE1 whole cell extract) on Day 113. Boost is defined as at 
least a 2-fold increase from pre-boost sample taken at Day 78.  
 The GMFR against each pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole 
cell extract): 
 On Days 29, 78, 113, 169, and 254 over baseline (Day 1) 
 On Days 113, 169, and 254 over pre-boost (Day 78) 
 The maximum over baseline on either Day 29 or 78 (post-priming response) 
 The maximum over pre-boost (Day 78) on any of the Days 113, 169, or 254 
(post-boost response) 
 The maximum during the study. 
 The GMT against each pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole 
cell extract): 
 On Days 29, 78, 113, 169, and 254 
 The maximum on Days 29 or 78 (after priming dose) 
 The maximum after Days 113, 169, or 254 (after boosting dose) 
 The maximum during the study. 
2.5.3 
Secondary Colonization Endpoints 
 Proportion of subjects with positive B. pertussis by bacterial culture of nasal sample 
collected on each day and on any day (Days 92, 96, and 113). 
 B. pertussis colony counts on each day (Days 92, 96, and 113). 
 Number of subjects who remain culture positive for B. pertussis at Days 78 (following 
priming) and 254 (following boost). 

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2.5.4 
Secondary Safety Endpoints 
 Unsolicited AEs (eg, treatment-emergent AEs, SAEs, and suspected unexpected serious 
adverse reactions [SUSARs]) collected for 28 days following each vaccination by 
Medical Dictionary for Regulatory Activities (MedDRA) classification and severity 
score. 
 Unsolicited AEs related to vaccination through Day 113 by MedDRA classification and 
severity score. 
 Serious AEs through 6 months following the last vaccination (or until resolved or stable) 
by MedDRA classification, relatedness, and severity score. 
 Vital sign measurements with severity scoring immediately following vaccination. 
2.6 
Exploratory Endpoint 
 Cell-mediated (eg, B cell, CD4 T lymphocytes + T cell, CD8 T lymphocytes + T cell) 
responses (eg, cell staining, cytokine production) following stimulation of PBMC 
collected at baseline, and 8 days post-vaccination (prime and boost) to pertussis-specific 
antigens. Results expressed both as absolute values and fold over baseline (per specific 
assay characteristics). 
 Following the outcomes of the primary and secondary analyses, additional exploratory 
endpoints may be tested for systemic or nasal mucosal immunogenicity (IgG or IgA) 
responses at any time point collected and not already performed in the primary or 
secondary analysis sets. 
 The GMT, expressed for serum IgG ELISA against tetanus and diphtheria on Days 29 
and 113. 

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3 
Investigational Plan 
3.1 
Study Design 
This is a multi-center, randomized, placebo-controlled, and observer-blinded trial with a 
6-month safety follow-up after the last vaccination. After signing the informed consent form 
(ICF), subjects will be enrolled in the trial and screened over a window of 30 days; screening 
will include obtaining a nasal sample for mucosal pertussis immune status. Subjects will also 
be asked to provide a signed ICF for the use of samples for further pertussis-specific testing 
or assay development. On Day 1, eligible subjects will be randomized to 1 of 4 treatment 
arms and receive BPZE1 intranasal vaccine or formulation buffer for injection (placebo) (via 
the VaxINator atomization device) and a licensed aP comparator vaccine (ie, Boostrix) or 
sterile normal saline (placebo), given by IM injection. To maintain the blind throughout the 
trial period, placebo vaccination via intranasal and IM routes, using formulation buffer and 
normal saline, respectively will be included, and unblinded pharmacy staff will manage 
vaccine logistics, preparation, and (if needed) administration but will not be involved in 
study-related assessments or have subject contact for data collection after study vaccine 
administration. Approximately 300 subjects will be randomly assigned 2:1 for the first 
(prime) vaccination with 200 subjects assigned to BPZE1 vaccination and 100 subjects 
assigned to Boostrix (aP vaccine) vaccination. During the second (boosting) vaccination, half 
of each of the treatment groups will be further randomly assigned to receive BPZE1 or 
placebo resulting in a 2:2:1:1 randomization scheme (Table 3-1).  
Table 3-1 
Dosing Scheme 
Timing 
Day 1 
Day 85 
Treatment Arm 
Nasal Vaccination 
IM Vaccination 
Nasal Vaccination 
BPZE1 
Placeboa 
Boostrix 
Placebob 
BPZE1 
Placeboa 
A (N = 100)
X
-
-
X
X
-
B (N = 100)
X
-
-
X
-
X
C (N = 50)
-
X
X
-
X
-
D (N = 50)
-
X
X
-
-
X
Abbreviation: IM, intramuscular. 
a  
Intranasal application of 2 × 0.4 mL (0.4 mL per nostril) placebo (formulation buffer). 
b  
IM injection of 0.5 mL placebo (normal saline) to the deltoid region. 
As part of the screening procedures, all subjects will provide a nasal sample for 
determination of mucosal (S-IgA) pertussis antibody status, with this sample collected at 
least 6 days prior to randomization. Day 1 vaccination (primary) will be delivered by 

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intranasal application (BPZE1 or placebo) and by IM injection into the deltoid (Boostrix [aP 
vaccine] or placebo), with subjects randomly assigned to receive 1 of the 4 final treatment 
regimens. Nasal secretion sampling for mucosal antibody response (S-IgA ELISA) to 
pertussis-specific antigens will occur at baseline (screening) and on Days 29 and 78 
post-primary vaccination. Serum sampling for antibody response (IgA and IgA ELISA) will 
occur at baseline (Day 1 and prior to primary vaccination) and on Days 29 and 85 (prior to 
boosting vaccination). Subjects will be tested for BPZE1 clearance (colonization) from the 
nasal tract via a standard nasal secretion sampling on Day 78 and used for pertussis culture 
and colony count. There needs to be at least 6 days between the nasal secretion sampling, 
which will occur at Visit 4 (Day 78), and the boosting intranasal vaccination. The boosting 
vaccination visit (Day 85 [+7 days]) will consist of all subjects receiving intranasal 
administration (BPZE1 or placebo) with half of the subjects who received BPZE1 for the 
primary vaccination receiving a second dose of BPZE1 and the other half of subjects 
receiving placebo (Table 3-1). Similarly, half of the subjects receiving Boostrix will receive 
BPZE1 and half will receive placebo. Colonization following the boosting vaccination will 
be measured on Days 92, 96, and 113 by standard nasal secretion sampling. Any subject who 
tested positive by pertussis culture on Day 113 will be retested on Day 254 or at the time of 
the end-of-study visit. Chronic carriage of BPZE1 has not been reported (ie, the majority of 
subjects have been clear at Day 29 and no subject has had positive cultures at Day 46) and is 
therefore not expected. Any subject who remains positive at Day 254 will be provided a short 
course of azithromycin, which is clinically used to eradicate B. pertussis from the 
nasopharynx. Should a subject be allergic to azithromycin, an appropriate antibiotic will be 
substituted that has effectiveness against B. pertussis. Mucosal (S-IgA ELISA) and serum 
response (IgG and IgA ELISA) to pertussis-specific antigens after boosting will be tested on 
Days 113, 169, and 254.  
The first 48 subjects randomly assigned will be designated the safety lead-in cohort and will 
be sequentially enrolled by escalating dose. The first 24 subjects will be randomly assigned 
as noted above in a ratio of 2:1 to receive active product of either an intranasal dose of 
107 CFU of BPZE1 or IM Boostrix. These subjects will be followed through Day 8 with 
safety laboratory tests, reactogenicity, and AE assessments with daily review by the medical 
monitory for activation of any halting rule. Following accumulation of all safety data through 
Day 8 post-vaccination, the 24 additional subjects will be randomly assigned 2:1 to receive 
active products of either an intranasal dose of 109 CFU of BPZE1 or IM Boostrix. To 

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maintain the blind for intranasal and IM administered products, all subjects will receive 
appropriate placebo vaccinations. All safety lead-in subjects will have safety laboratory 
testing at baseline (screening), and on Days 8, 85 (prior to vaccination), and 92. The medical 
monitor has the authority to request a review by the SMC should a halting rule be initiated or 
there are any other safety concerns. The SMC will convene after the subjects in the entire 
safety lead-in cohort (both dose levels) have completed Day 8 (Visit 2) and will review all 
safety data through Day 8 (reactogenicity and safety laboratory results) and any AEs which 
have occurred since study initiation. The SMC will be authorized to allow the remainder of 
the subjects to be randomly assigned (see Table 3-2). The randomization scheme for the 
safety lead-in will follow the same scheme as the full cohort for the second vaccination 
(keeping at either 107 CFU or 109 CFU based on initial dosing assignment) such that half the 
BPZE1 and half the Boostrix vaccinated subjects will receive intranasal BPZE1 vaccination 
on Day 85 and the other half will receive placebo. 
Table 3-2 
Dosing and Safety Lead-In Cohort 
BPZE1 
Dose 
BPZE1 
Boostrix 
Trigger to advance 
Review Process 
Advancing to 
107 
N = 16 
N = 8 
Day 8 safety on 107 dosing 
cohort
Pause rules; daily 
medical monitor reviews
109 safety lead-in 
109 
N = 16 
N = 8 
Day 8 safety on full safety 
lead-in cohort; all adverse 
events to date
Safety Monitoring 
Committee review 
Full cohort 
All subjects will be monitored for 60 minutes after vaccine administration on Days 1 and 85. 
After the subjects have been monitored for 60 minutes post-vaccination, vital signs will be 
collected and a post-vaccination examination for reactogenicity (local, nasal/respiratory, and 
systemic) with toxicity grade will be completed.  
Subjects will receive a daily subject diary on Days 1 and 85 after each vaccination. All 
subjects will record reactogenicity in the daily subject diary starting the same day of the 
primary (Day 1) and boosting (Day 85) vaccinations and for 7 additional days (not counting 
vaccination day). For primary vaccination site-specific local (arm), nasal/respiratory, general 
systemic reactogenicity reactions, and other unsolicited symptoms/complaints (including 
start and stop dates) will be recorded and standard toxicity grading will be applied by the 
investigator at the next visit (Visit 2). For the boost vaccination, nasal/respiratory, general 
systemic reactogenicity reactions, and other unsolicited symptoms/complaints (including 
start and stop dates) will be recorded and standard toxicity grading will be applied by the 

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investigator at the next visit (Visit 6). The clinical staff will review the information from the 
subject diaries with the subjects on Days 8 and 92 (Visits 2 and 6). Should any reactogenicity 
event extend beyond 7 days post-vaccination and be clinically significant by toxicity grade 1 
or greater, then it will be entered as an AE with the same start date as the reactogenicity event 
and followed to resolution. 
All AEs will be monitored through 28 days after the primary and boosting vaccinations. 
Unsolicited AEs related to vaccination will be monitored through Day 113 (unless resolved 
or felt to be stable at an earlier date). Serious AEs will be monitored to the end of the study. 
The primary database lock will occur on Day 113, and all data collected through Day 113 
will be included in the clinical study report (CSR) and submitted to regulatory authorities. A 
subsequent longer-term safety follow-up, including longer-term persistence of immune 
responses, will occur through Day 254. These data will be provided, following a second 
database lock, in an addendum to the CSR. Subjects will return to the clinical site on Day 
254 (±15 days) for end-of-study procedures. 
A subset of no more than 60 subjects (randomly assigned to the 109 CFU dose) will opt in to 
provide blood samples for PBMCs harvested on Days 1, 8, and 92. 
Blood or blood cell samples may be stored frozen by ILiAD or companies working for 
ILiAD for up to 10 years. 
3.1.1 
Rationale of Study Design 
In order to advance BPZE1 into later stage licensure trials, demonstration of an adequate 
immune response (mucosal and/or serum immunity) is necessary. As BPZE1 is a mucosal 
immunogen first and foremost, the IgA response is likely to be of key importance. Since 
regulators are accustomed to seeing the IgG response and IgG is known to be important for 
long-term protection against disease, this parameter will also be assessed. In addition, 
demonstrating boosting and persistence of the immune response with BPZE1 is critical. As 
aP vaccines are given as boosters to the adult population, describing the immune response to 
BPZE1 following aP vaccination is of interest. Understanding these responses relative to 
subject’s baseline mucosal and serum immunity is of interest. The common pertussis 
antigens found in acellular products (PT, PRN, FHA, and FIM 2/3) will be measured in 
serum samples (IgG and IgA) and a specific whole cell pertussis ELISA (based on BPZE1) 
will be measured in mucosal (S-IgA) and serum (IgG). As the concentration of individual 

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antigens is vastly reduced in BPZE1 compared to aP vaccines, it is not anticipated that 
BPZE1 will have the same magnitude of immune response to the antigens found in acellular 
products. However, demonstration of a measurable response akin to that seen with whole cell 
pertussis vaccines is anticipated and a measurable response to a whole cell pertussis ELISA 
provides additional immunological evidence. Development of assays for additional markers 
of immunity may be needed. 
Nasal vaccination with BPZE1 has been shown to induce temporary nasal colonization 
followed by clearance, which is thought to be the result of development of mucosal 
immunity. The level of colonization/clearance following a 2-course vaccination series is of 
interest using this higher dose of BPZE1 and it is anticipated that prior vaccination with 
BPZE1 will result in rapid mucosal immune response to a second vaccination (boosting) and 
may avert/reduce colonization at the time of boosting. It is anticipated that prior vaccination 
with aP will not induce the same protection against colonization as compared to prior 
vaccination with BPZE1 and therefore a greater proportion of subjects will become colonized 
following boosting with BPZE1. Prior immunization with aP may result in a boosted serum 
immune response (IgG) to the pertussis antigens found in Boostrix when subjects then 
receive BPZE1. Whether prior aP immunization can also enhance the serum IgA response to 
these pertussis antigens following BPZE1 vaccination is uncertain. Immunization with 
BPZE1 should result in a measurable whole cell pertussis antibody response (IgG and IgA). 
A second vaccination with BPZE1 is expected to boost this immunological response. 
However, it is not anticipated that aP would induce a measurable whole cell pertussis 
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4 
Subject Selection and Withdrawal Criteria 
4.1 
Selection of Study Population 
Approximately 300 subjects will be enrolled at 3 to 5 clinical sites in the United States. 
Subjects will be assigned to study vaccine only if they meet all the inclusion criteria and none 
of the exclusion criteria. 
Deviations from the inclusion and exclusion criteria are not allowed because they can 
potentially jeopardize the scientific integrity of the study, regulatory acceptability, or subject 
safety. Therefore, adherence to the criteria as specified in the protocol is essential. 
4.1.1 
Inclusion Criteria 
Each subject must meet all the following criteria to be enrolled in this study: 
1. Is a male or nonpregnant female 18 to 50 years of age, inclusive, on Day 1 (primary 
vaccination). 
2. Is capable of understanding the written informed consent, provides signed and 
witnessed written informed consent, and agrees to comply with protocol 
requirements. 
3. Female subjects must be nonpregnant and nonlactating and meet 1 of the following 
criteria:  
a) Postmenopausal (defined as 12 consecutive months with no menses without an 
alternative medical cause or documented plasma follicle-stimulating hormone 
level in the postmenopausal range); 
b) Surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral 
oophorectomy).  
NOTE: These procedures and laboratory test results must be confirmed by physical 
examination, or by subject recall of specific data and hospital/facility of procedure, or by 
medical documentation of said procedure. 
c) Is of childbearing potential (defined as any female who has experienced menarche 
and who is NOT permanently sterile or postmenopausal), agrees to be 
heterosexually inactive from at least 21 days prior to enrollment and through 

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3 months after the boosting vaccination or agrees to consistently use any of the 
following methods of contraception from at least 21 days prior to enrollment and 
through 3 months after the boosting vaccination: 
i. Condoms (male or female) with spermicide 
ii. Diaphragm with spermicide 
iii. Cervical cap with spermicide 
iv. Intrauterine device 
v. Oral or patch contraceptives 
vi. Norplant®, Depo-Provera®, or other FDA-approved contraceptive 
method that is designed to protect against pregnancy.  
NOTE: Periodic abstinence (eg, calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
4. Has a stable health status as assessed by the investigator, as established by physical 
examination, vital sign measurements, and medical history. 
5. Has access to a consistent and reliable means of telephone contact, which may be in 
the home, workplace, or by personal mobile electronic device. 
6. Is able to understand and comply with planned study procedures. 
7. Lives a reasonable distance from the clinical site to be able to travel to and from the 
clinical site for follow-up visits and agrees to go to the clinical site for evaluation (or 
provide medical record access if evaluated elsewhere) in the event of an AE.  
8. Agrees to stay in contact with the clinical site for the duration of the study, has no 
current plans to move from the study area, and provides updated contact information 
as necessary. 
4.1.2 
Exclusion Criteria 
Subjects meeting any of the following criteria will be excluded from the study: 
1. History of being vaccinated in the past 5 years against pertussis (subject recall). 
2. Any significant past reaction to any component of Boostrix (at the discretion of the 
investigator). 

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3. Subject reported diagnosis of pertussis in the past 10 years (must be laboratory 
confirmed or physician diagnosed from medical records). 
4. Vital signs by toxicity scoring >1 (may be repeated once during the screening period 
to allow for inclusion and the most recent measurement taken at baseline). 
5. Chronic illness being treated actively and with evidence of recent intervention for 
worsening or fluctuating symptoms (at the discretion of the investigator). 
6. The subject has a history of active cancer (malignancy) in the last 10 years 
(exception is subjects with adequately treated non-melanomatous skin carcinoma, 
who may participate in the study). 
7. Current use of any smoking products and unwillingness to refrain from the use of 
any smoking products from screening through 28 days after the boosting 
vaccination. 
8. Use of narcotic drugs, evidenced by urine toxicology screen or a history of 
drug/alcohol abuse within the past 2 years. 
9. Has donated blood or suffered from blood loss of more than 450 mL (1 unit of 
blood) within 60 days prior to screening, or donated plasma within 14 days prior to 
screening. 
10. Receipt of immunoglobulin, blood-derived products, systemic corticosteroids, or 
other immunosuppressant drugs within 90 days prior to Day 1. 
11. Asthma*, obstructive nasal canal, recurrent or acute sinusitis or other chronic 
respiratory problems inclusive of the diagnosis of any significant pulmonary disease. 
*Asthma as diagnosed with spirometry showing reversibility of disease and must 
meet at least Step 1 classification with current prescription/use of medications to 
control symptoms (EPR-3 2007). 
12. History of nasal surgery or Bell’s palsy. 
13. Use of repeated nasal sprays, Neti pot, or nasal washing within the past 1 month 
(more than 2 times per week). Subjects must agree to refrain from use of any of 
these modalities through Day 113. 

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14. A temporary exclusion to vaccinate if acute respiratory tract infection or rhinorrhea 
or temperature >100.4°F (no symptoms for 3 days prior to Vaccination Day). 
Subjects may be vaccinated if they stay within the vaccination window (screening 
[30 days] or at the time of the booster [10 days]. 
NOTE: If a subject exceeds the screening window, they must be reconsented and 
screening must be reinitiated. 
15. Use of corticosteroids in the respiratory tract (eg, nasal steroids, inhaled steroids) 
within 30 days prior to Day 1.  
16. Receipt of a licensed vaccine within the last 30 days prior to Day 1 or planned 
vaccination during the active study conduct through Day 113. In the case of seasonal 
influenza, vaccination should not be withheld and is not contraindicated for subject 
participation. However, vaccination should be planned outside of a 30-day pre- and 
30-day post-vaccination window whenever possible. 
17. Known hypersensitivity to any component of the study vaccines. 
18. Participation in any other clinical trial for the testing of an unlicensed product during 
the previous 6 months or planned during the study conduct. 
NOTE: “Testing” is intended to mean receipt of an investigational product. Subjects in 
long term safety follow-up studies where vaccination has been completed greater than 6 
months prior to this study enrollment are allowed. 
19. Inability to adhere to the protocol, including plans to move from the area. 
20. Personal history or family (first degree) history of congenital or hereditary 
immunodeficiency.  
21. Past or present infection with human immunodeficiency virus, hepatitis B, or 
hepatitis C by screening test. 
22. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic). 
NOTE: Stable endocrine disorders that have a confirmed autoimmune etiology (eg, 
thyroid, pancreatic) are allowed. 

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23. Any neurological disease or history of significant neurological disorder (eg, 
meningitis, seizures, multiple sclerosis, vasculitis, migraines*, Guillain-Barré 
syndrome [genetic/congenital or acquired]).*Significant neurological migraine 
includes frequent migraine (2 times a month or greater), migraine with aura or 
migraine with complications (status migraninosus, persist aura without infarction, 
infarction or aura triggered seizure defined by International Classification of 
Headache Disorders-3 [ICHD-3 2018]). 
24. Any medical condition that, in the opinion of the investigator, might interfere with 
the evaluation of the study objectives or might affect the safety of the individual, eg, 
major depression or history of suicidal attempt. 
25. Toxicity grading >1 for screening laboratory test results for specific kidney, hepatic, 
and hematologic values for all subjects and in screening laboratory values for the 
safety cohort as indicated in Table 13-2 (may be repeated once during the screening 
period to allow for inclusion and the most recent measurement taken at baseline). 
See Table 13-2 for specifically designed parameters.  
26. Body mass index <17 kg/m2 or >40 kg/m2. 
27. Frequent contact with children less than 1 year of age (parent, childcare worker, 
nurse, etc.) or residence in the same household as persons with known 
immunodeficiency including persons on immunosuppressant therapy. 
28. Study team member or first-degree relative of study team member. 
4.2 
Withdrawal of Subjects From Study Treatment and/or the Study 
The duration of the study is defined for each subject as the date signed written informed 
consent is provided through the last follow-up visit on Day 254. 
4.2.1 
Reasons for Withdrawal/Discontinuation 
Subjects may withdraw or discontinue from the study at any time and for any reason without 
prejudice to their future medical care by the investigator or at the study center. Every effort 
should be made to keep subjects in the study. The reasons for subjects not completing the 
study will be recorded. A subject may be withdrawn from the study or study treatment (ie, no 
longer receive study vaccine) for any of the following reasons: 

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1. Failure to continue to meet the protocol inclusion or exclusion criteria. 
2. Noncompliance with the protocol. 
3. Serious or intolerable AE(s) that in the investigator’s opinion requires withdrawal or 
discontinuation from the study.  
4. The subject has laboratory safety results that reveal clinically significant 
hematological or biochemical changes from the baseline values. 
5. The subject has symptoms or an intercurrent illness not consistent with the protocol 
requirements or that justify withdrawal or discontinuation. 
6. The subject is lost to follow-up. 
7. Other reasons (eg,  development of contraindications of use of study drug, use of 
disallowed substances). 
8. If pregnancy occurs further vaccination will be discontinued. 
9. The subject withdraws consent or the investigator or ILiAD Biotechnologies decides 
to discontinue the subject’s participation in the study. 
The investigator will also withdraw a subject if ILiAD Biotechnologies terminates the study. 
Upon occurrence of a serious or intolerable AE, the investigator will confer with the sponsor. 
If a subject is discontinued because of an AE, the event will be followed until it is resolved. 
Any subject may withdraw his or her consent at any time. 
4.2.2 
Handling of Withdrawals 
Subjects are free to withdraw from the study or study treatment at any time upon request. 
Subject participation in the study may be stopped at any time at the discretion of the 
investigator or at ILiAD Biotechnologies request. 
Subjects who discontinue study treatment or active participation in the study will no longer 
receive study vaccination but will continue to be followed and are not considered withdrawn. 
When a subject withdraws from the study, the reason(s) for withdrawal shall be recorded by 
the investigator on the relevant page in the electronic case report form (eCRF).  
All subjects who discontinue from study treatment prematurely will follow the same visit 
schedule as other subjects without further vaccination. 

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Whenever possible, all subjects who discontinue from the study prematurely will stay in the 
study for safety reasons and will follow the schedule of events (Table 13-1) if they have 
received vaccination. Subjects who fail to return for final assessments will be contacted by 
the clinical site in an attempt to have them comply with the protocol. A subject will not be 
considered lost to follow-up until every attempt to contact the subject has been made, at 
minimum 2 (documented) phone calls, followed by a registered letter. Every effort should be 
made to collect safety data on subjects through the end-of-study visit. 
It is vital to obtain follow-up data on any subject withdrawn from the study or study vaccine 
(ie, no longer receiving study vaccination) because of an AE or serious AE (SAE). In every 
case, efforts must be made to undertake protocol-specified safety follow-up procedures. 
4.2.3 
Replacements 
Subjects who withdraw, are withdrawn or terminated from this study, or are lost to follow-up 
after signing the ICF but before receipt of any study vaccine may be replaced. Subjects who 
receive the study vaccine and subsequently withdraw, are discontinued from receiving further 
vaccination, are terminated from the study, or are lost to follow-up will not be replaced. 
5 
Study Treatments 
5.1 
Method of Assigning Subjects to Treatment Groups 
Subjects will be randomly assigned to 1 of 4 treatment arms, in a 2:2:1:1 ratio, as presented 
in Table 3-1. An interactive response technology will be used to administer the randomization 
schedule centrally. Biostatistics will generate the randomization schedule using SAS® 
software Version 9.3 or later (SAS Institute Inc, Cary, North Carolina) for the interactive 
response technology, which will link sequential subject randomization numbers to treatment 
codes. The randomization schedule will be created by the dedicated randomization team, 
stored in a separate project area, and will be blinded to the project team with the exception of 
the unblinded pharmacy staff who will manage vaccine logistics, preparation, and 
administration, but will not be involved in study-related assessments or have subject contact 
for data collection following study vaccine administration. 

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5.2 
Treatments Administered 
Subjects in Treatment Arm A (N = 100) will receive an intranasal application of 2 × 0.4 mL 
(0.4 mL per nostril containing half the dose 5 × 108 bacteria to give a total dose of 109 CFU) 
BPZE1 and an IM injection of 0.5 mL placebo (sterile normal saline) to the deltoid region on 
Day 1 and an intranasal application of 2 × 0.4 mL (0.4 mL per nostril containing half the dose 
5 × 108 bacteria to give a total dose of 109 CFU) BPZE1 on Day 85. Note: the first 
24 subjects will be assigned to the 107 CFU dose. 
Subjects in Treatment Arm B (N = 100) will receive an intranasal application of 2 × 0.4 mL 
(0.4 mL per nostril containing half the dose 5 × 108 bacteria to give a total dose of 109 CFU) 
BPZE1 and an IM injection of 0.5 mL placebo (sterile normal saline) to the deltoid region on 
Day 1 and an intranasal application of 2 × 0.4 mL (0.4 mL per nostril) placebo (formulation 
buffer) on Day 85. Note: the first 24 subjects will be assigned to the 107 CFU dose.  
Subjects in Treatment Arm C (N = 50) will receive an intranasal application of 2 × 0.4 mL 
(0.4 mL per nostril) placebo (formulation buffer) and an IM injection of 0.5 mL Boostrix (aP 
vaccine, manufactured by GlaxoSmithKline, Research Triangle Park, North Carolina) to the 
deltoid region on Day 1 and an intranasal application of 2 × 0.4 mL (0.4 mL per nostril 
containing half the dose 5 × 108 bacteria to give a total dose of 109 CFU) BPZE1 on Day 85. 
Note: the first 24 subjects will be assigned to the 107 CFU dose. 
Subjects in Treatment Arm D (N = 50) will receive an intranasal application of 2 × 0.4 mL 
(0.4 mL per nostril) placebo (formulation buffer) and an IM injection of 0.5 mL Boostrix (aP 
vaccine), to the deltoid region on Day 1 and an intranasal application of 2 × 0.4 mL (0.4 mL 
per nostril) placebo (formulation buffer) on Day 85. Note: the first 24 subjects will be 
assigned to the 107 CFU dose. 
The dose of BPZE1 active ingredient will be administered to the subject within 60 minutes of 
removal from the freezer. One milliliter of WFI will be used to reconstitute the 1 mL vial of 
lyophilized BPZE1, but only 0.8 mL of vaccine will be withdrawn for administration into 
both nostrils. Following reconstitution, the VaxINator will be attached to the syringe, and 
0.4 mL volume will be administered to each nostril. In the case of placebo nasal vaccination, 
a similar volume of WFI will be reconstituted into a vial containing only lyophilized buffer, 
followed by 0.4 mL volume administered into each nostril with the vaccinator. The 
VaxINator provides a uniform, controlled delivery, which allows the vaccinator to accurately 

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deliver 0.4 mL of vaccine to the initial nostril and then administer the remaining 0.4 mL to 
the opposite nostril.  
The study vaccine will be labeled according to manufacturer specifications and include the 
statement “Caution: New Drug – Limited by Federal Law to Investigational Use.” 
5.3 
Identity of Investigational Product 
The BPZE1 investigational vaccine is for intranasal administration and is an off-white 
lyophilized cake that contains genetically modified, live B. pertussis strain BPZE1 bacteria in 
lyophilization buffer.  
ILiAD Biotechnologies will provide the CRO with the investigational vaccine and 
lyophilized buffer and the CRO will ensure proper labelling and distribution to the clinical 
sites. 
The following supplies will be used for vaccination in the study: 
Product 
Dosage and Route of Administration: 
BPZE1 
2 × 0.4 mL (0.4 mL per nostril containing 
half the dose 5 × 108 bacteria to give a total 
dose of 109 CFU) administered intranasally 
by syringe + VaxINator 
aP (Boostrix vaccine; manufactured by 
GlaxoSmithKline) 
0.5 mL administered by IM injection to the 
deltoid region as active control 
Intranasal placebo 
2 × 0.4 mL (0.4 mL per nostril) reconstituted 
lyophilized buffer administered intranasally 
by syringe + VaxINator 
IM placebo 
0.5 mL sterile normal saline USP 
administered by IM injection to the deltoid 
region 
Abbreviations: aP, acellular pertussis; CFU, colony-forming units; IM, intramuscular; USP, United States 
Pharmacopeia. 
The intranasal placebo consists of lyophilized buffer diluted with sterile WFI which, is the 
same constituents in the same quantities as the BPZE1 investigational vaccine, absent the 
attenuated B. pertussis cells. The IM placebo is sterile normal saline (eg, normal saline).  

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Each vaccination with BPZE1 or Boostrix will utilize a single vial/syringe of product for 
each single use (1:1 assignment from study drug accountability). See pharmacy manual for 
specifics on product preparation. 
5.3.1 
Study Drug Packaging and Storage 
The primary packaging for BPZE1 is a sterile glass 2R DIN vial with a chlorobutyl 
lyophilization stopper. The vial closure system is a combination of the stopper and the 
aluminum cap. The vials are crimped directly after the lyophilization process using the 
automated Fill & Finish unit that filled the vials with 1.0 mL suspension. The intranasal 
placebo dose contains the lyophilized buffer (ie, the vaccine formulation without the BPZE1 
attenuated bacteria) and packaged in similar fashion. 
Sufficient supplies of 1 vial for each subject in the clinical trial will be provided, with 
approximately 30% spare vials, packaged in a box of 49 vials for the BPZE1 drug product 
and 41 vials per box for the placebo. The vials and the boxes will be labeled with the required 
information applicable to investigational vaccine or placebo product used in clinical trials. 
The boxes either contain the vaccine or the placebo (lyophilized buffer only).  
The 18G (or larger) needles, WFI, and syringes capable of holding 1 mL WFI used to 
reconstitute the investigational vaccine or placebo (formulation buffer) vials will be stored 
separately from the investigational vaccine vials at ambient temperature.  
Boostrix will be procured from commercial stock and supplied as either single dose vials or 
prefilled syringes containing a 0.5 mL suspension for injection. The IM placebo is sterile 
normal saline United States Pharmacopeia (from a commercial supplier) and is supplied in a 
similar fashion. 
Vaccines and placebos must be stored in a secure area (eg, locked room or locked 
refrigerator), protected from light and moisture as required by manufacturer. Vaccine will be 
shipped from ILiAD’s European contract manufacturing organization to the CRO’s 
repository and distribution center and should be stored at –20°C or below prior to shipping to 
the clinical sites, where the vaccine will be stored at –10°C or below. Clinical sites will store 
the vaccine in order to maintain viability of BPZE1 prior to reconstitution with WFI. The 
exposure of reconstituted BPZE1 to room temperature prior to vaccination should not exceed 

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60 minutes. A detailed description regarding the storage, reconstitution, and handling the 
investigational vaccines will be in the Pharmacy Manual. 
Boostrix should be stored at 2°C to 8°C.  
5.3.2 
Investigational Product Accountability 
The investigator will maintain accurate records of receipt of all study vaccine and placebo 
vials, including dates of receipt. In addition, accurate records will be kept regarding when 
and how much study vaccine is dispensed and used by each subject in the study. Reasons for 
departure from the expected dispensing regimen must also be recorded. At the completion of 
the study, to satisfy regulatory requirements regarding drug accountability, all study vaccine 
will be reconciled and retained or destroyed according to applicable regulations. No study 
vaccine will be destroyed until authorized in writing by the sponsor. 
5.3.3 
Other Supplies 
Other clinical supplies that will be provided to the clinical sites for distribution to subjects 
include subject diaries, a measuring tool for measuring injection site erythema and swelling, 
and a thermometer for measuring body temperature.  
A single VaxINator kit (sterile pouch containing a VaxINator atomization devise, a 1-mL 
single-use syringe, and other accessories not used in this protocol) is provided for each 
intranasal vaccination. The VaxINator boxes will be labeled with the required information 
applicable to a medical device accessory, for clinical trial investigational use only. The 
VaxINator is manufactured by Teleflex Medical. Teleflex has DMF #025388 for the 
VaxINator. The VaxINator is a conical shape plastic component that Luer-locks onto a 1-mL 
syringe. The VaxINator atomizes the liquid vaccine as it exits the syringe. The conical shape 
forms a plug in the nostril and high applied-pressure atomizes the liquid into a fine mist. 
Kits for serum immune collection, mucosal immune collection, PBMCs and mucosal 
pertussis culture will all be provided and in sufficient quantity to allow for each subject 
sample collection. Bar coding will be applied to allow for sample tracking at the time of 
collection and throughout storage, transport, and testing. 
Adequate supplies for immunization of individuals including, 18G (or larger) needles for 
injection, syringes, normal saline, nasal vaccinators, and blinding tape will be supplied. The 

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WFI will be provided for reconstituting the investigational vaccine and placebo vials for 
nasal immunization and will be stored separately from the investigational vaccine vials, at 
ambient temperature in a secure area.  
5.4 
Overdose Management 
An overdose is any dose of study treatment given to a subject or taken by a subject that 
exceeds the dose described in the protocol. Any overdose, with or without associated AEs, 
must be promptly reported to the CRO’s pharmacovigilance reporting center. In case of any 
AEs associated with the overdose, these should be reported on relevant AE/SAE sections in 
the eCRF. Any overdose should be recorded as a protocol violation and promptly reported to 
the sponsor. No overdoses are expected as the vaccine and adjuvant will be administered by 
clinical staff. 
5.4.1 
Treatment of Overdose 
Treatment of overdose would include supportive and symptomatic care, according to the 
standards of care at the site. The investigator should promptly notify the medical monitor 
about the overdose and seek his/her input on the medical management, as needed. 
5.5 
Blinding 
This is an observer-blinded study. To maintain the blind, placebo vaccination via intranasal 
and IM routes will be included and unblinded pharmacy staff will manage vaccine logistic, 
preparation, and administration (when necessary) so as to maintain the blind from the 
remainder of the study personnel and subjects. The pharmacy staff will not be involved in 
study-related assessments or have subject contact for data collection following study vaccine 
administration. 
The full database lock will occur on Day 113 and all data collected through Day 113 will be 
included in the CSR and submitted to regulatory authorities. A subsequent longer-term safety 
follow-up, including longer-term persistence of immune responses, will occur through 
Day 254. These data will be provided in an addendum to the CSR. The clinical site study 
team directly participating in subject contact/care will remain blinded to the treatment 
assignment during this extended safety follow-up period. All unblinded data analyses prior to 
full database lock on Day 113 will be handled by the unblinded team of statisticians and 

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programmers. A strict firewall between the blinded and unblinded teams will be maintained 
during study conduct. 
5.5.1 
Breaking the Blind Due to Medical Emergency 
A subject’s treatment assignment will not be broken until the end of the study for the clinical 
site study team unless medical treatment of the subject depends on knowing the study 
treatment the subject received. In the event that the blind needs to be broken because of a 
medical emergency, the investigator may unblind an individual subject’s treatment allocation.  
As soon as possible, the investigator should first contact the medical monitor to discuss the 
medical emergency and the reason for revealing the actual treatment received by that subject. 
The treatment assignment will be unblinded through interactive response technology. 
Reasons for treatment unblinding must be clearly explained and justified in the eCRF. The 
date on which the code was broken together with the identity of the person responsible must 
also be documented. 
5.6 
Treatment Compliance 
The study vaccination will be administered to maintain the blind to site personnel conducting 
subject assessments. The location (in case of IM administration, right or left arm), date, and 
timing of all product administrations will be recorded in the subjects’ eCRF. Compliance will 
be determined by the number and percentage of subjects who receive study vaccination. Any 
deviations from the dosing schedule outside the defined visit windows (Table 13-1) will be 
flagged in the clinical database.  
5.7 
Prior Vaccinations and Concomitant Therapy 
Administration of medications, therapies, or vaccines will be recorded in the eCRF. 
Concomitant medications will include all medications (including vaccines) taken by the 
subject from the time of signing the ICF through 28 days after the boosting vaccination (or 
through the early termination visit if prior to that time). Intake will include whether there was 
knowledge of past pertussis vaccination and (when available) the year of receipt. Prescription 
and over-the-counter drugs will be included, as well as herbals, vitamins, and supplements. 
In addition, receipt of nonstudy vaccines will be solicited through approximately 28 days 
after the boosting vaccination and reported in the eCRF. 

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Use of new medication should prompt evaluation for the presence of a new diagnosis of 
chronic medical disease or condition. Medications that might interfere with the evaluation of 
the study vaccines should not be used during the study-reporting period unless clinically 
indicated as part of the subject’s health care. New medications may indicate a new onset 
medical condition. As an example, the use of a bronchodilator medication due to wheezing 
(new prescription) will be used along with signs and symptoms to define a medically 
significant wheezing AE. 

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6 
Study Assessments and Procedures 
Before performing any study-related procedures, the investigator will explain the study to 
potential subjects and all potential subjects will be given an ICF to read and sign. Subjects 
will have the opportunity to have any questions answered before signing the ICF. The 
investigator must address all questions raised by the subject. The investigator or designee 
will also sign the ICF and a copy of the ICF will be given to the subjects. In addition, 
subjects will be asked to provide a signed informed consent for the use of samples for further 
pertussis-specific testing or assay development. The subjects will also be informed that a 
urine drug screen may be performed, at the discretion of the investigator, on any subject who 
experiences an AE. The schedule of events by study visit is shown in Table 13-1. 
6.1 
Demographic and Baseline Data 
Demographic and baseline data such as date of birth (day, month, and year), sex, race, 
ethnicity, weight, height, and body mass index should be collected at screening and recorded 
in the subject’s eCRF. 
6.2 
Medical History 
A complete medical history (including prior and concomitant medical conditions, 
surgeries/significant procedures for medical conditions [eg, endoscopy, uterine ablation] 
history of past tobacco use) will be collected at screening. If the year of past pertussis 
vaccination is known by the subject this will be entered as part of the medical history (eg, 
Tdap booster). 
6.2.1 
Concomitant Medication 
Concomitant medications include all known medications (including herbal supplements, 
multivitamins and over-the-counter medications) taken by the subject from the time of 
signing the informed consent through 28 days after the boosting vaccination (or through early 
termination visit if prior to that time). Concomitant medications received associated with an 
SAE will be collected throughout the study period. 

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6.3 
Safety Assessments 
Safety assessments for all subjects will include the following: vital sign measurements, 
targeted symptom directed physical examination, clinical safety laboratory tests (screening 
for all subjects, safety cohort to have additional testing), reactogenicity (post-vaccination), 
AEs and the occurrence of SAEs. These assessments are detailed in Sections 6.3.1 through 
6.3.6.  
The first 48 subjects randomly assigned will be designated the safety lead-in cohort and will 
have additional safety laboratory testing performed on Days 8, 85 (prior to vaccination), and 
92. 
6.3.1 
Vital Sign Measurements 
Vital sign measurements will include oral temperature, pulse rate, and diastolic and systolic 
blood pressure (after subject is seated for at least 5 minutes). Subjects must not eat or drink 
anything hot or cold within 10 minutes prior to taking oral temperature. Vital signs will be 
toxicity graded per the FDA toxicity (Table 13-3). 
Vital signs will be collected at screening and on Days 1 (before vaccine administration and 
60 minutes [±15 minutes] after vaccine administration [before subject is discharged]), 8, 29, 
85 (before vaccine administration and 60 minutes [±15 minutes] after vaccine administration 
[before subject is discharged]), 92, 96, and 113.  
6.3.2 
Post-vaccination Evaluation 
On Days 1 and 85, subjects will be monitored for 60 minutes after vaccine administration. 
Details regarding collecting and reporting site-specific local and nasal/respiratory and 
systemic reactogenicity symptoms are presented in Section 6.3.5.3. Subject diaries will be 
distributed according to Table 13-1 and will be used to record site-specific local, 
nasal/respiratory, and systemic reactions. Solicited local, nasal/respiratory, and systemic 
reactogenicity will be graded by the investigator at the return visit (Days 8 and 92). Should 
any reactogenicity event extend beyond 7 days post-vaccination and be clinically significant 
by toxicity grade 1 or greater, then it will be entered as an AE with the same start date as the 
reactogenicity event and followed to resolution. 

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In addition, a measuring tool for measuring injection site erythema and swelling and a 
thermometer for measuring body temperature will also be distributed.  
After the subject has been monitored for 60 minutes after vaccination, the following 
evaluations will be performed: 
1. Obtain vital sign measurements (oral temperature, pulse rate, and diastolic and 
systolic blood pressure) at 60 minutes (±15 minutes) after vaccination. Vital signs 
will be toxicity graded per the FDA toxicity (Table 13-3). 
2. Complete an injection site examination for reactogenicity (local, nasal/respiratory, 
and systemic) and toxicity grade (see Section 6.3.5.3) at 60 minutes (±15 minutes) 
after vaccination. 
6.3.3 
Complete Physical Examination 
A full physical examination will be completed at screening and will include the following: an 
assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, abdomen, 
lymph nodes, musculoskeletal system/extremities, and neurological system. Height and 
weight will be measured at the screening visit only. 
A targeted or symptom-directed physical examination will be performed as mentioned in the 
schedule of events for all subjects on Days 1, 8, 29, 85, 92, 96, and 113 (Table 13-1). On 
Days 1 and 85, this physical examination is done before vaccination. For unscheduled visits, 
targeted symptom directed physical examinations will be performed at the discretion of the 
investigator, if necessary, to evaluate AEs or clinical laboratory abnormalities. 
6.3.4 
Clinical Safety Laboratory Tests 
Clinical safety laboratory tests will include the following and will be collected as mentioned 
in the schedule of events for all subjects at screening and for the safety lead-in cohort at 
screening, and Days 8, 85 (prior to vaccination), and 92 (Table 13-1): 
 Hematology: hemoglobin, white blood cell count and differential, and platelet count. 
 Chemistry panel: sodium, potassium, glucose (random), blood urea nitrogen, creatinine, 
calcium, albumin, total protein, bilirubin, alanine aminotransferase, and aspartate 
aminotransferase 

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 Coagulation: Prothrombin time/international normalized ratio and partial thromboplastin 
time 
For the full cohort, toxicity scoring of >1 for hemoglobin, white blood count, platelets, 
creatinine, alanine aminotransferase, aspartate aminotransferase, bilirubin, prothrombin time 
and partial thromboplastin time will be used as exclusionary criteria (Table 13-2). For the 
safety cohort all laboratory tests noted in Table 13-2 with toxicity score >1 will be used as 
exclusionary criteria. For the safety cohort being followed with additional scheduled safety 
labs, should any laboratory value result in a grade 3 or greater toxicity score this lab must be 
entered as an adverse event and followed with retesting and observing for resolution or new 
clinical baseline. In the case of an alternative explanation for the abnormal laboratory (eg, 
urinary tract infection with an elevated WBC) the illness should be the AE classification. 
Investigators should determine if any laboratory values resulting in a grade 2 toxicity score 
should be entered as an AE, with repeat testing based on clinical judgement and the 
laboratory value of concern. 
6.3.4.1 
Serology 
Serology testing will be collected at screening and will include hepatitis B, hepatitis C, and 
human immunodeficiency virus.  
6.3.4.2 
Urine Drug Screen 
A urine drug screen will be performed at screening and will include the following 
non-prescription drugs of abuse: opiates, cocaine, phencyclidine, amphetamines, 
benzodiazepines, and methadone.  
At the discretion of the investigator a urine drug screen may be performed on any subject 
who experiences an AE. 
6.3.4.3 
Urine Pregnancy Test 
For female subjects of childbearing potential, a urine pregnancy test will be performed at 
screening and prior to vaccination on Days 1 and 85. 

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6.3.5 
Adverse Events 
6.3.5.1 
Definitions of Adverse Events 
The investigator is responsible for reporting all AEs that are observed or reported during the 
study, regardless of their relationship to study vaccination or their clinical significance. 
An AE is defined as any untoward medical occurrence in a subject enrolled into this study 
regardless of its causal relationship to study vaccination. Subjects will be instructed to 
contact the investigator at any time after randomization if any symptoms develop.  
6.3.5.2 
Serious Adverse Events 
An SAE is defined as any event that 
 results in death 
 is immediately life threatening 
 requires inpatient hospitalization or prolongation of existing hospitalization 
 results in persistent or significant disability/incapacity 
 is a congenital anomaly/birth defect 
Important medical events that may not result in death, be life threatening, or require 
hospitalization may be considered SAEs when, based upon appropriate medical judgment, 
they may jeopardize the subject or may require medical or surgical intervention to prevent 
one of the outcomes listed in this definition. Examples of such medical events include 
allergic bronchospasm requiring intensive treatment in an emergency room or at home, 
blood dyscrasias or convulsions that do not result in inpatient hospitalization, or the 
development of drug dependency or drug abuse. 
At the discretion of the investigator, a urine drug screen may be performed on any subject 
who experiences an SAE. 
6.3.5.3 
Site-Specific and General Systemic Reactogenicity Symptoms 
Subjects will receive a daily subject diary on Days 1 and 85 after each vaccination. All 
subjects will record reactogenicity in the daily subject diary starting the same day of the 
primary (Day 1) and boosting (Day 85) vaccinations and for 7 additional days (after each 

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vaccination, not counting vaccination day). Reactogenicity events are common and known to 
occur following administration of these types of vaccinations. For primary vaccination site-
specific local (arm), nasal/respiratory, general systemic reactogenicity reactions, and other 
unsolicited symptoms/complaints, including start and stop dates will be recorded and the 
investigator will apply a standard toxicology grading at the subsequent visit (Table 6-1). For 
the boosting vaccination, nasal/respiratory, general systemic reactogenicity reactions, and 
other unsolicited symptoms/complaints, including start and stop dates will be recorded and 
then toxicity graded by the investigator (Table 6-1). The clinical staff will review the 
information from the subject diary with the subjects on Days 8 and 92. The subject diary will 
be collected from the subjects and stored as a source document. Should any reactogenicity 
event extend beyond 7 days post-vaccination and be clinically significant by toxicity grade 1 
or greater, then it will be entered as an AE with the same start date as the reactogenicity event 
and followed to resolution. The following toxicity grading scales will be used to grade 
solicited local, nasal/respiratory, and systemic reactions:  
Table 6-1 
Toxicity Grading Scales 
Local Reactogenicity Grading 
Local Reaction to 
Injectable Product 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4) 
Pain 
Does not interfere 
with activity 
Repeated use of 
nonnarcotic pain 
reliever >24 hours or 
interferes with 
activity 
Any use of narcotic 
pain reliever or 
prevents daily 
activity 
Emergency room 
visit or 
hospitalization 
Tenderness 
Mild discomfort to 
touch 
Discomfort with 
movement 
Significant 
discomfort at rest 
Emergency room 
visit or 
hospitalization 
Erythema/rednessa 
2.5 to 5 cm 
5.1 to 10 cm 
>10 cm 
Necrosis or 
exfoliative 
dermatitis 
Induration/swellingb 
2.5 to 5 cm and 
does not interfere 
with activity 
5.1 to 10 cm or 
interferes with 
activity 
>10 cm or prevents 
daily activity 
Necrosis 
Nasal/Respiratory Reactogenicity Grading 
Local Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Runny nose 
Noticeable but does not 
interfere with daily 
activity 
Moderate discomfort that 
interferes with daily 
activity 
Significant 
discomfort/prevents daily 
activity or seeks medical 

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Nasal/Respiratory Reactogenicity Grading 
Local Reaction 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
care 
Stuffy nose/congestion 
Noticeable but does not 
interfere with daily 
activity 
Moderate discomfort that 
interferes with breathing 
from nose 
Unable to breathe through 
nose or seeks medical care 
Nasal pain/irritation 
Noticeable but does not 
interfere with daily 
activity 
Moderate discomfort that 
interferes with daily 
activity 
Significant discomfort that 
prevents daily activity or 
seeks medical care 
Epistaxis 
Total duration of all 
episodes in a 24-hour 
period <30 minutes 
Total duration of all 
episodes in a 24-hour 
period >30 minutes 
Any bleeding that required 
visit for medical encounter 
Sneezing 
Noticeable but does not 
interfere with daily 
activity 
Moderate discomfort that 
interferes with daily 
activity 
Significant discomfort; 
prevents daily activity 
Sinus pressure/pain 
Noticeable but does not 
interfere with daily 
activity 
Moderate discomfort that 
interferes with daily 
activity 
Significant discomfort that 
prevents daily activity or 
seeks medical care 
Sore/irritated throat 
Noticeable but does not 
interfere with eating or 
drinking 
Moderate discomfort that 
interferes with eating or 
drinking 
Significant discomfort that 
prevents eating or drinking 
or seeks medical care 
Cough 
Noticeable but does not 
interfere with daily 
activity or sleeping 
Frequent cough that 
interferes with daily 
activity or sleeping 
Prevents daily activity, 
prevents sleep, or seeks 
medical care 
Shortness of 
breath/wheezing 
Noticeable but does not 
interfere with daily 
activity 
Moderate discomfort that 
interferes with daily 
activity 
Significant discomfort/ 
prevents daily activity or 
seeks medical encounter 
Subjective Systemic Reactogenicity Grading 
Systemic (Subjective) 
Mild (Grade 1) 
Moderate (Grade 2) 
Severe (Grade 3) 
Feverc - orald 
100.4°F – 101.1°F 
101.2°F – 102.0°F 
>102.0°F 
Fatigue (tiredness) 
No interference with daily 
activity 
Some interference 
with daily activity 
Significant interference, 
prevents daily activity 
Malaise (general 
unwell feeling) 
No interference with daily 
activity 
Some interference 
with daily activity 
Significant interference, 
prevents daily activity 
Myalgia (body 
aches/muscular pain) 
No interference with daily 
activity 
Some interference 
with daily activity 
Significant interference, 
prevents daily activity 
Arthralgia (joint pain) 
No interference with daily 
activity 
Some interference 
with daily activity 
Significant interference, 
prevents daily activity 
Headache 
No interference with daily 
activity 
Some interference 
with daily activity 
Significant interference, 
prevents daily activity 
Rash/hypersensitivitye 
Pruritus OR local rash 
Diffuse rash 
Diffuse rash with blisters or 
mouth ulcerations, 
anaphylaxis, or angioedema 

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Note: Grade 0 will be the classification if the observation is less than a Grade 1. 
a 
In addition to grading the measured local reaction at the greatest single diameter, the measurement should 
be recorded as a continuous variable. 
b 
Induration/swelling should be evaluated and graded using the functional scale as well as the actual 
measurement. 
c 
A fever can be considered not related to the study product if an alternative etiology can be documented. 
d 
Subjects must not eat or drink anything hot or cold within 10 minutes prior to taking oral temperature. Oral 
temperature assessed on Day 1 prior to the first study vaccination will be considered as baseline. 
e 
Adapted from the Division of AIDS Table for Grading the Severity of Adult and Pediatric Adverse Events 
Version 2. 2014.  
Source: DHHS 2007 
6.3.5.4 
Assessing and Documenting Adverse Events 
Safety will be assessed by the frequency and severity of: 
1. Serious AEs occurring from the time of vaccination through the end of the study. 
2. Solicited reactogenicity – reactogenicity events occurring from the time of each study 
vaccination through 7 days after each study vaccination: 
a. Nasal/respiratory reactions including runny nose, stuffy nose/congestion, nasal 
pain/irritation, epistaxis, sneezing, sinus pressure/pain, sore/irritated throat, cough, 
and shortness of breath/wheezing. 
b. Systemic reactions including fever, fatigue, malaise, myalgia, arthralgia, headache, 
and rash/hypersensitivity. 
c. Local reactions – pain, tenderness, erythema/redness, induration/swelling  
3. Unsolicited AEs – all AEs regardless of causality, will be collected for 28 days after 
each vaccination. Adverse events related to vaccination will be collected through 
Day 113. Between screening (signing of ICF) and Day 1, AEs will be collected if 
classifies as serious or if related to study procedure or study involvement. Any AE that 
results in vaccination delay (eg, temporary exclusions due to acute illness or fever, or 
investigator determined medical condition) during screening or during study conduct 
will also be recorded as an AE. Any newly identified potential AE of special interest 
will be followed through Day 254. 
4. Any scheduled safety laboratory value that results in a Grade 3 toxicity score in the 
safety cohort will be recorded as an AE. Recording will be appropriate for either the 

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variable itself (eg, elevated creatine) or the condition which is diagnosed (eg, 
dehydration or chronic renal insufficiency). 
At every study visit, subjects will be asked a standard nonleading question to elicit any 
medically related changes in their well-being. They will also be asked if they have been 
hospitalized, had any accidents, used any new medications, or changed concomitant 
medication regimens (both prescription and over-the-counter medications). 
In addition to subject observations, AEs identified from any study data (eg, laboratory values, 
physical examination findings) or identified from review of other documents (eg, subject 
diaries) that are relevant to subject safety will be documented on the AE page in the eCRF. 
6.3.5.5 
Reporting Adverse Events 
All AEs reported or observed during the study will be recorded on the AE page in the eCRF. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational) product. The occurrence of an AE may come to the attention of study 
personnel during study visits and interviews of a study recipient presenting for medical care, 
or upon review by a study monitor. 
Adverse events not meeting the protocol-defined criteria for SAEs will be captured on the 
appropriate data collection form and eCRF. Information to be collected for unsolicited 
nonserious AEs includes event description, date of onset, licensed study physician’s 
assessment of severity and relationship to study product and alternate etiology (if not related 
to study product), date of resolution of the event, seriousness, and outcome. Adverse events 
occurring during the collection and reporting period will be documented appropriately 
regardless of relationship (as defined in Section 6.3.5.4). 
Any medical condition that is present at the time that the subject is screened will be 
considered as baseline and not reported as an AE; however, if the severity of any pre-existing 
medical condition increases, it will be recorded as an AE. 
Adverse events must be graded for severity and assessed for relationship to study product. 
Adverse events characterized as intermittent require documentation of onset and duration of 

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each episode. The start and stop date of each reported AE will be recorded on the appropriate 
data collection form and eCRF. 
Adverse events resulting from concurrent illnesses, reactions to concurrent illnesses, 
reactions to concurrent medications, or progression of disease states must also be reported. 
All AEs will be followed to adequate resolution. The MedDRA will be used to code all AEs. 
6.3.5.6 
Reporting Serious Adverse Events 
Any AE that meets SAE criteria (Section 6.3.5.2) must be reported to the CRO immediately 
(ie, within 24 hours) after the time site personnel first learn about the event. The contact 
information to be used for SAE reporting will be provided to the CRO and the CRO will 
oversee the SAE reporting. 
6.3.5.7 
Suspected Unexpected Serious Adverse Reactions and 
Nonserious Adverse Events of Special Interest 
The sponsor will promptly evaluate all SUSARs and nonserious AEs of special interest 
against cumulative product experience to identify and expeditiously communicate possible 
new safety findings to investigators, institutional review boards (IRBs), and applicable health 
authorities based on applicable legislation. 
To determine reporting requirements for single AE cases, the sponsor will assess the 
expectedness of these events using the following reference documents: 
 study vaccination investigator's brochure 
The sponsor will compare the severity of each SUSAR and the cumulative event frequency 
reported for the study with the severity and frequency reported in the applicable reference 
document. 
Reporting requirements will also be based on the investigator's assessment of causality and 
seriousness, with allowance for upgrading by the sponsor as needed. 

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6.3.5.8 
Assessment of Severity 
The severity, or intensity, of an AE refers to the extent to which an AE affects the subject’s 
daily activities. The intensity of the AE will be rated as mild, moderate, or severe using the 
following criteria: 
Mild 
(Grade 1): 
These events require minimal or no treatment and do not interfere with the 
subject’s daily activities. 
Moderate 
(Grade 2): 
These events result in a low level of inconvenience or concern with the 
therapeutic measures. Moderate events may cause some interference with 
normal functioning. 
Severe 
(Grade 3): 
These events interrupt a subject’s usual daily activity and may require systemic 
drug therapy or other treatment. Severe events are usually incapacitating. 
 
Changes in the severity of an AE should be documented to allow an assessment of the 
duration of the event at each level of intensity to be performed. Adverse events characterized 
as intermittent require documentation of onset and duration of each episode. 
6.3.5.9 
Assessment of Causality 
The investigator’s assessment of an AE’s relationship to study vaccination is part of the 
documentation process, but it is not a factor in determining what is or is not reported in the 
study. If there is any doubt as to whether a clinical observation is an AE, the event should be 
reported. 
The relationship or association of the test article in causing or contributing to the AE will be 
characterized using the following classification and criteria: 
 Related – There is a reasonable possibility that the study vaccination caused the AE. 
Reasonable possibility means that there is evidence to suggest a causal relationship 
between the study vaccination and the AE. 
 Not Related – There is not a reasonable possibility that the administration of the study 
vaccination caused the event. 

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6.3.5.10 
Follow-up of Subjects Reporting Adverse Events 
All AEs must be reported in detail on the appropriate page in the eCRF and followed to 
satisfactory resolution, until the investigator deems the event to be chronic or not clinically 
significant, or until the subject is considered to be stable. Adverse events will be collected, 
assessed, and followed through resolution based on Section 6.3.5.4. Serious AEs will be 
collected, assessed, and followed through end of study or until satisfactory resolution or 
clinically stable. 
Resolution of an AE/SAE is defined as the return to pretreatment status or stabilization of the 
condition with the expectation that it will remain chronic. 
If the investigator becomes aware of an acute febrile illness and the investigator decides to 
bring the subject in for an evaluation to determine etiology, then the investigator, at their own 
discretion, can determine the specific testing that should be performed. Follow-up 
procedures, evaluations, and outcomes will be recorded on the appropriate data collection 
form. 
6.3.6 
Immunogenicity Assessments 
At least 6 days prior to vaccination (during screening and on Day 78), and on Days 29, 113, 
169, and 254 a mucosal nasal secretion collection will be taken using a nasal secretion 
collection device for testing of mucosal antibodies (S-IgA) to pertussis antigens. The 
mucosal nasal secretion collected at screening will only be tested if the subject is randomized 
into the study unless consent is provided to use the sample for assay development needs 
specific to this vaccine program. 
On Days 78 (after a mucosal collection is completed), 92, 96, and 113 (after a mucosal 
collection is completed) a nasal secretion sample will be taken for pertussis culture. Any 
subject who tested positive for pertussis culture at Day 113 will also have a nasal secretion 
sample taken for pertussis culture on Day 254.  
Blood samples will be taken on Days 1 (prior to primary vaccination), 29, 85 (prior to 
boosting vaccination), 113, 169, and 254 for testing of serum pertussis antibodies (IgG and 
IgA ELISA) to pertussis antigens.  

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A subset of no more than 60 subjects (randomly assigned to the 109 CFU dose) will opt in to 
provide blood samples for PBMC harvesting on Days 1, 8, and 92. 
The details on the handling, processing, and shipping of immunogenicity samples will be 
provided in the Laboratory Manual.  
6.4 
Halting Rules 
Further enrollment and study vaccinations will be halted (paused) for SMC 
review/recommendation if any of the following are reported: 
 Any subject experiences ulceration, abscess, or necrosis in the nose that is considered 
to be related to study product administration, through 28 days following the boosting 
vaccination. 
 Any subject experiences laryngospasm, bronchospasm, or anaphylaxis within 1 day 
after administration of study vaccination that is considered to be related to study 
vaccination. 
 Three or more subjects experience generalized urticaria grade 3 or higher within 
3 days after administration of study vaccination that is considered to be related to 
study vaccination. 
 Any subject experiences a study product-related SAE from the time of the primary 
vaccination through the subject’s last study visit on Day 254. 
 Any subject experiences acute weakness of limbs and/or cranial nerve innervated 
muscles (description of potential signal of Guillain-Barré syndrome) after 
administration of study vaccination, through 28 days following the boosting 
vaccination. 
This study will also be halted for SMC review/recommendation if, within 8 days after 
administration of each study vaccination, the following occurs: 
 5% of subjects experience the same severe study product-related subjective systemic, 
local, or mucosal reaction, for which the severity (grade) is corroborated by study 
personnel. 
Grading scales for solicited reactions are included in Section 6.3.5.3. 

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If any of the halting rules are met following any subject receipt of study vaccination, then 
this study will not continue with the remaining enrollments or future vaccination without a 
review by and recommendation from the SMC to proceed. Vaccination windows will be 
adjusted for any such pause to allow subjects to remain within the expected schedule of 
events. All events that classify for halting rules will be entered as adverse events. 
ILiAD retains the authority to suspend additional enrollment and study interventions or 
administration of study product during the entire study, as applicable. 
6.5 
Pregnancy 
Pregnancy is not regarded as an AE unless there is a suspicion that an investigational vaccine 
may have interfered with the effectiveness of a contraceptive medication. Any pregnancy that 
occurs during study participation must be reported using a clinical study pregnancy form. To 
ensure subject safety, each pregnancy must be reported to the sponsor, ILiAD 
Biotechnologies, within 2 weeks of learning of its occurrence. If pregnancy occurs further 
vaccination will be discontinued. The pregnancy must be followed-up to determine outcome 
(including spontaneous miscarriage, elective termination, normal birth, or congenital 
abnormality) and status of mother and child, even if the subject was discontinued from the 
study. Pregnancy complications and elective terminations for medical reasons must be 
reported as an AE or SAE. Spontaneous miscarriages must be reported as an SAE. 
Any pregnancy, brought to the investigator’s attention after the subject has completed the 
study, but occurring while the subject was in the study, must be promptly reported to ILiAD 
Biotechnologies. 
6.6 
Laboratory Analyses 
Any abnormal laboratory test results (hematology, chemistry, or coagulation) resulting in a 
grade 3 or greater toxicity score which is associated with the scheduled safety cohort follow 
up testing must be entered as an adverse event and followed with retesting and observing for 
resolution. If an underlying disease or new condition is identified that accounts for the 
elevation than this should be documented as the adverse event.  
Any clinically significant safety assessments that are associated with the underlying or new 
onset condition for which laboratory testing occurs during the course of the study will not be 

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entered as adverse events per se, rather the new onset or worsening condition should be 
entered as judged by the investigator. 
6.7 
Sample Collections 
Procedures for the handling and processing of biological samples are provided in the 
Laboratory Manual or the Site Manual.  
The hematology, coagulation, and chemistry laboratory analyses will be performed at a 
central laboratory. Laboratory data will be graded according to the FDA Toxicity Grading 
Scale (Table 13-2) and will be adjusted according to local laboratory reference ranges. 
The samples collected for immunogenicity (B and T cell) testing and pertussis culture will be 
stored in appropriate conditions as specified in the Laboratory Manual until shipped for 
testing at a facility designated by the sponsor. 
Subjects will be asked to provide a signed informed consent for the use of samples for further 
pertussis-specific testing or assay development. Aliquots of collected samples from this study 
may be retained for additional testing of antigens specific to B. pertussis for a maximum of 
10 years (starting from the date at which the last subject had the last study visit), unless local 
rules, regulations, or guidelines require different timeframes or different procedures, in 
accord with subject consent. Testing for colonization using B. pertussis culture following the 
primary vaccination and post-boosting vaccination will also occur.  

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7 
Statistical and Analytical Plan 
The primary objectives of this study are to assess nasal mucosal immune response S-IgA 
following intranasal vaccination with BPZE1 (109 CFU) when used as a single (eg, prime) or 
2-dose (eg, prime + boost) series and reactogenicity (all) and specific safety laboratory 
parameters (safety lead-in cohort only) following intranasal vaccination with BPZE1 (109 
CFU), in healthy volunteers 18 to 50 years of age. This study is designed as a randomized, 
placebo-controlled, observer-blinded clinical trial evaluating the safety and immunogenicity 
of 1 or 2 doses of 109 CFU of BPZE1 delivered by intranasal VaxINator device or Boostrix 
delivered by IM injection. To maintain the blind, placebo vaccination via IM and intranasal 
routes will be included. 
The primary database lock will occur on Day 113 and all data collected through Day 113 will 
be included in the CSR and submitted to regulatory authorities. A subsequent longer-term 
safety follow-up, including longer-term persistence of immune responses, will occur through 
Day 254. These data will be provided in an addendum to the CSR. The clinical site study 
team directly participating in subject contact/care will remain blinded to the treatment 
assignment during this extended safety follow up period. All unblinded data analyses prior to 
primary database lock at Day 113 will be handled by the unblinded team of statisticians and 
programmers. A strict firewall between the blinded and unblinded teams will be maintained 
during study conduct. 
This Phase 2b study is not designed to test a formal null hypothesis. Rather, it is intended to 
obtain preliminary assessment of the safety and immunogenicity induced by the BPZE1 
lyophilized vaccine in healthy adults. 
7.1 
Primary Immunogenicity and Safety Endpoints 
Immunogenicity:  
 Mucosal seroconversion (nasal mucosal secretion sampling): Proportion of subjects 
who achieve seroconversion against at least 1 pertussis antigen (PT, FHA, PRN, FIM 
2/3, or BPZE1 whole cell extract) in nasal secretions on Day 29 or 113 (prime or prime 
+ boost). 
Mucosal seroconversion is defined as a 2-fold increase over the baseline value (collected 
during screening) or a 4-fold increase over the minimal limit of assay detection 

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(whenever the baseline value falls below the limits of assay detection) for any of the 
pertussis-specific antibodies (S-IgA ELISA): PT, FHA, PRN, FIM 2/3, or BPZE1 whole 
cell extract). Seroconversion will be calculated based on absolute titer response over 
baseline and by standardizing pertussis-specific ELISA responses relative to 
non-pertussis-specific total nasal mucosal secretion (eg, IgA). To be further defined 
during assay development and within the statistical analysis plan. 
Mucosal baseline samples will be taken at the screening visit. 
Safety: 
 Solicited AEs (local, nasal/respiratory, and systemic reactogenicity events) for 7 days 
following each vaccination by severity score, duration, and peak intensity. Local 
reactogenicity will only be monitored following the IM vaccination. 
 Safety laboratory results (serum chemistry, hematology, coagulation) by FDA toxicity 
score (change from baseline or absolute toxicity score as defined in Table 13-2) in the 
safety lead-in cohort at Day 8 following each vaccination. In the case of no toxicity 
classification the score of 0 will be assigned. 
7.2 
Secondary Immunogenicity and Safety Endpoints  
Systemic Immunogenicity (serum sampling [expressed separately for IgG, IgA, and 
IgG or IgA ELISA when possible): 
 Proportion of subjects who achieve seroconversion against pertussis antigen (PT, FHA, 
PRN, FIM 2/3, or BPZE1 whole cell extract) over baseline for: 
 At least 1 antigen on each of the Days 29, 85, 113, 169, or 254 
 At least 1 antigen on any of the Days 29, 85, 113, 169, or 254 
 At least any 1 antigen on all Days 29, 85, 113, 169, or 254 
Systemic seroconversion is defined as a 2-fold increase over the baseline value or a 
4-fold increase over the minimal limit of assay detection (whenever the baseline value 
falls below the limits of assay detection). Both IgG and IgA ELISA will measure 
antibodies against the following pertussis-specific antigens of PT, FHA, PRN, and FIM 
2/3, and IgG ELISA will measure antibodies against broader pertussis-specific antigens 
in BPZE1 whole cell extract. 

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Serum baseline samples will be taken at Day 1 prior to vaccination. 
 Proportion of subjects who achieve seroconversion (IgG ELISA only) against BPZE1 
whole cell extract over baseline: 
 On either Day 29 (prime) or 113 (boost) 
 On both Days 29 (prime) and 113 (boost). 
 Proportion of subjects who achieve seroconversion against the aP antigens PT, FHA, and 
PRN over baseline: 
 On either Day 29 (prime) or 113 (boost) 
 On both Days 29 (prime) or 113 (boost). 
 Proportion of subjects who achieve seroconversion against 2 or more pertussis antigens 
(PT, FHA, PRN, FIM 2/3, and BPZE1 whole cell extract) over baseline: 
 On each of the Days 29, 85, 113, 169, or 254 
 On any of the Days 29, 85, 113, 169, or 254 
 At least the same 2 antigens on all Days 29, 85, 113, 169, and 254. 
 Proportion of subjects who demonstrate boosting for each pertussis antigen (PT, FHA, 
PRN, FIM 2/3, and BPZE1 whole cell extract) on Day 113. Boost is defined as at least a 
2-fold increase from the pre-boost sample taken on Day 85. 
 The GMFR against each pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole 
cell extract): 
 On Days 29, 85, 113, 169, and 254 over baseline (Day 1) 
 On Days 113, 169, and 254 over pre-boost (Day 85) 
 The maximum over baseline on either Day 29 or 85 (post-priming response) 
 The maximum over pre-boost (Day 85) on any of the Days 113, 169, or 254 
(post-boost response) 
 The maximum during the study. 

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 The GMT against each pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole 
cell extract): 
 On Days 29, 85, 113, 169, and 254 
 The maximum on Day 29 or 85 (after priming dose) 
 The maximum after Days 113, 169, or 254 (after boosting dose) 
 The maximum during the study. 
Mucosal Immunogenicity S-IgA ELISA (nasal mucosal secretion sampling): 
 Proportion of subjects who achieve seroconversion against any pertussis-specific antigen 
(PT, PRN, FHA, FIM 2/3, or BPZE1 whole cell extract) over baseline: 
 At least 1 antigen on each of the Days 29, 78, 113, 169, or 254 
 At least 1 antigen on any of the Days 29, 78, 113, 169, or 254 
 At least any 1 antigen on all Days 29, 78, 113, 169, and 254. 
 Proportion of subjects who achieve seroconversion against BPZE1 whole cell extract 
over baseline: 
 On either Day 29 (prime) or 113 (boost) 
 On both Days 29 (prime) and 113 (boost). 
 Proportion of subjects who achieve seroconversion against aP antigens PT, FHA, and 
PRN over baseline: 
 On either Days 29 (prime) or 113 (boost) 
 On both Days 29 (prime) and 113 (boost). 
 Proportion of subjects who achieve seroconversion for any 2 or more pertussis antigens 
(PT, PRN, FHA, or BPZE1 whole cell extract) over baseline: 
 On each of Days 29, 78, 113, 169, or 254 
 On any of Days 29, 78, 113, 169 or 254 
 At least the same 2 antigens on all Days 29, 78, 113, 169, and 254. 

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 Proportion of subjects who demonstrate boosting against each pertussis antigen (PT, 
FHA, PRN, FIM 2/3, and BPZE1 whole cell extract) on Day 113. Boost is defined as at 
least a 2-fold increase from pre-boost sample taken at Day 78.  
 The GMFR against each pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole 
cell extract): 
 On Days 29, 78, 113, 169, and 254 over baseline (Day 1) 
 On Days 113, 169, and 254 over pre-boost (Day 78) 
 The maximum over baseline on either Day 29 or 78 (post-priming response) 
 The maximum over pre-boost (Day 78) on any of the Days 113, 169, or 254 
(post-boost response) 
 The maximum during the study. 
 The GMT against each pertussis antigen (PT, FHA, PRN, FIM 2/3, and BPZE1 whole 
cell extract): 
 On Days 29, 78, 113, 169, and 254 
 The maximum on Days 29 or 78 (after priming dose) 
 The maximum after Days 113, 169, or 254 (after boosting dose) 
 The maximum during the study. 
Colonization: 
 Proportion of subjects with positive B. pertussis by bacterial culture of nasal sample 
collected on each day and on any day (Days 92, 96, and 113). 
 B. pertussis colony counts on each day (Days 92, 96, and 113). 
 Number of subjects who remain culture positive for B. pertussis at Days 78 (following 
priming) and 254 (following boost). 
Safety: 
 Unsolicited AEs (eg, treatment-emergent AEs, SAEs, and SUSARs) collected for 
28 days following each vaccination by MedDRA classification and severity score.  

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 Unsolicited AEs related to vaccination through Day 113 by MedDRA classification and 
severity score. 
 Serious AEs, through 6 months following the last vaccination (or until resolved or 
stable) by MedDRA classification, relatedness, and severity score. 
 Vital sign measurements with severity scoring immediately following vaccination. 
7.3 
Exploratory Endpoints 
 Cell-mediated (eg, B cell, CD4 T lymphocytes + T cell, CD8 T lymphocytes + T cell) 
responses (eg, cell staining, cytokine production) following stimulation of PBMCs 
collected at baseline, and 8 days post-vaccination (prime and boost) to pertussis-specific 
antigens. Results expressed both as absolute values and fold over baseline (per specific 
assay characteristics). 
 Following the outcomes of the primary and secondary analyses, additional exploratory 
endpoints may be tested for systemic or nasal mucosal immunogenicity (IgG or IgA) 
responses at any time point collected and not already performed in the primary or 
secondary analysis sets. 
 The GMT, expressed for serum IgG ELISA against tetanus and diphtheria on Days 29 
and 113. 
7.4 
Sample Size Calculations 
A total of 300 subjects will be globally assigned at 2:2:1:1 allocation ratio and receive 
BPZE1 intranasal administration with placebo IM or Boostrix IM with placebo intranasal 
administration on Day 1 and BPZE1 or placebo intranasal administration on Day 85 (See 
Section 5.2). This sample size is based on clinical considerations but not a statistical power 
analysis as the study does not test any formal null hypothesis. Table 7-1 presents the width of 
95% CI for selected certain sample sizes under response rate assumptions (defined based on 
nasal mucosal immunogenicity) between 50% and 90%. Calculations were performed using 
PASS v12. 

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Table 7-1 
95% Confidence Interval and Width for Selected Response Rate 
Assumptions for Relevant Treatment Arm Sample Sizes 
Response 
Rate (%) 
N = 50 
N = 100 
N = 200 
N = 250 
CI (%) 
Width 
(%) 
CI (%) 
Width 
(%) 
CI (%) 
Width 
(%) 
CI (%) 
Width 
(%) 
50 
35.5, 64.5 
28.9 
39.8, 60.2 
20.3 
42.9, 57.1 
14.3 
43.6, 56.4 
12.7 
60 
45.2, 73.6 
28.4 
49.7, 69.7 
19.9 
52.9, 66.8 
14.0 
53.6, 66.1 
12.5 
70 
55.4, 82.1 
26.7 
60.0, 78.8 
18.7 
63.1, 76.3 
13.1 
63.9, 75.6 
11.7 
80 
66.3, 90.0 
23.7 
70.8, 87.3 
16.5 
73.8, 85.3 
11.5 
74.5, 84.8 
10.3 
90 
78.2, 96.7 
18.5 
82.4, 95.1 
12.7 
85.0, 93.8 
8.8 
85.6, 93.4 
7.8 
Abbreviation: N, sample size.  
Note: 
As described in the study design section, 200 subjects will receive a primary vaccination and 100 out 
of those 200 subjects will receive a boosting vaccination. In addition, 50 out of 100 active control subjects 
will receive a BPZE1 boost.  
7.5 
Analysis Sets 
The Safety Analysis Set will consist of all subjects who have received at least 1 dose of the 
study vaccine and have any safety data available. Subjects will be classified according to the 
vaccine actually received. The primary safety analysis will be done on this analysis set. 
The Intent to Treat Analysis Set will consist of all subjects who have been randomized to the 
study. Subjects will be classified according to the study group randomized. The data of 
subject disposition, demographics, and medical history will be summarized on this analysis 
set. 
The Immunogenicity Analysis Set will include all the Intent to Treat subjects who received 
the prime dose of the study vaccine(s) and have contributed both pre- and at least 
1 post-prime vaccination sample (mucosal or serum immunogenicity testing, respectively) 
for which valid results were reported and who have not received any component of a licensed 
pertussis vaccine in the 5 years through Day 113 of the study. Subjects will be classified 
according to the study vaccine received. For analysis of boosting, those subject who have 
received all vaccinations and have a pre- (Day 78 for mucosal and Day 85 for serum) and a 
post-boost immune sample (Day 113) for which valid results were reported will be utilized. 
Additional testing for maximum response will be assessed for those subjects who received all 
vaccinations and have both a baseline sample (screening or Day 1 depending on the sample 
type) and a sample at Day 113. Immune persistence will be assessed in those subjects who 
contribute to sampling at Days 169 and 254. 

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The Per Protocol Analysis Set will include all subjects in the Prime/Boost Immunogenicity 
Analysis Set, with the following exclusions: 
 Data from all available visits for subjects following the receipt of unsuitable 
investigational product (either via dispensed/assigned or delivered). 
 Data from all available visits for subjects found to be ineligible at baseline per 
Protocol Version 6.0. 
 Data from all visits for subjects following the use of major immune-modulators, 
immune suppressants, receipt of blood products, or use of forbidden nasal solutions 
(eg, sprays, washes, neti pot) from 30 days prior to Day 1 through Day 113. 
 Data from all visits for subjects following clinically significant protocol deviations 
that can affect the efficacy (immunogenicity) results. 
 Data from any visit that occurs substantially out of window as defined by exceeding 
30 days past the visit window or the time point whereby the follow-on visit should 
have occurred, whichever is most restrictive. Standard visit windows are described in 
schedule of events (Appendix 13.1).  
For analyses using the Per Protocol Analysis Set, subjects will be grouped based on study 
vaccines actually received. 
7.6 
Description of Subgroups to be Analyzed 
Immunogenicity endpoints (seroconversion, GMT, and GMFR) will be summarized by 
baseline negative and positive status of various pertussis antibodies (eg, any subject positive 
for PT, PRN, FHA, or FIM 2/3). Other subgroup analyses may be performed for selected 
factors, such as pertussis vaccination history, smoking status, or nasal spray use at study 
baseline or during the study. 
7.7 
Statistical Analysis Methodology 
Statistical analysis will be performed using SAS software Version 9.3 or later. Continuous 
variables will be summarized using the mean, 2-sided 95% CI of the mean, SD, median, 
minimum value, and maximum value. Categorical variables will be summarized using 

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frequency counts and percentages, as well as 2-sided 95% CI for proportions computed using 
Clopper-Pearson method. Graphics of reverse cumulative distribution of anti-pertussis 
antibody titers will be generated for Days 29 and 113. 
Where applicable, data analyses will be conducted for the prime period (prior to boosting) 
and boost period (at or post-boosting).  
Data will be listed in data listings.  
Further details of the planned statistical analyses, methods, and data conventions are 
described in the statistical analysis plan. 
No formal hypothesis will be tested in this study. 
7.7.1 
Analysis of Primary Immunogenicity Endpoint 
Summaries and analysis of immunogenicity data will be presented for the Immunogenicity 
and Per Protocol Analysis Set. For immunogenicity data in the prime period, subjects in the 
Prime Immunogenicity Analysis Set will be grouped into BPZE1 prime (A+B) and Boostrix 
prime (C+D) arms. For immunogenicity data in the boost period, subjects in the Boost 
Immunogenicity Analysis Set will be grouped to BPZE1 prime with BPZE1 boost (A), 
BPZE1 prime with no boost (B), Boostrix prime with BPZE1 boost (C) and Boostrix prime 
with no boost (D). In addition, as multiple antigens are being tested across vaccine 
combinations, all possible treatment group combinations will be displayed. For priming data 
analysis, the primary endpoint will be based on nasal mucosal immunogenicity change from 
screening, and for boost data analysis that will be based on screening and Day 78 prior to 
boost vaccination. The Immunogenicity and Per Protocol Analysis Sets will be used for 
sensitivity analysis. 
The proportion and 95% CI of subjects who achieve seroconversion at Day 29 for prime 
vaccination and Day 113 for boost vaccination will be analyzed. Seroconversion is defined as 
a 2-fold increase over the baseline value or a 4-fold increase over the minimal limit of assay 
detection in S-IgA ELISA from nasal secretions for any of the pertussis-specific antibodies 
(S-IgA ELISA): PT, FHA, PRN, FIM 2/3, or BPZE1 whole cell extract). Baseline is defined 
as the value at screening.  

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7.7.2 
Analysis of Primary Safety Endpoint 
All summaries and analyses will be presented over all subjects and by treatment arm for 
prime and boost periods whenever possible. The treatment arms are BPZE1 versus Boostrix 
in prime period. For boost period, treatment arms are BPZE1 prime with BPZE1 boost (A), 
BPZE1 prime with no boost (B), Boostrix prime with BPZE1 boost (C), and Boostrix prime 
with no boost (D). The combination of A + C (received BPZE1 on Day 85) and B + D (did 
not receive BPZE1 on Day 85) will be combined when assessing short term reactogenicity 
and AEs through Day 28 post-boost. 
Solicited AEs will be summarized by severity for each day after each study vaccination for 
7 days and as the maximum severity over all 7 days after each vaccination. Additionally, 
solicited AEs will be analyzed by taking the most severe response over the follow-up period, 
dichotomizing into a binary variable (none versus mild, moderate, or severe) to summarize 
the proportion (with exact 95% CIs) of subjects reporting each symptom, any local, mucosal, 
or general systemic symptom. Summaries of solicited AEs will be presented separately by 
treatment arm for the prime period and the boost period when applicable as mentioned in the 
previous paragraph. Should any reactogenicity event extend beyond 7 day post-vaccination 
and be clinically significant by toxicity grade of 1 or greater, than the event will be entered as 
an AE with the same start date as the reactogenicity event and followed to resolution.  
Clinical safety laboratory test results for the safety lead-in cohort will be classified per FDA 
toxicity scoring system (Table 13-2) based on test value and change from baseline when 
applicable (as defined in Table 13-2). Counts and percentages of subjects by toxicity 
classifications and classification shift from baseline will be presented in tabulations by 
treatment arm. The full cohort will have baseline safety values expressed as mean/median 
with standard error per treatment group(s). 
7.7.3 
Analysis of Secondary Immunogenicity Endpoint 
The secondary nasal mucosal immunogenicity endpoints will be summarized by treatment 
arm. Analyses will include the GMTs along with corresponding 95% CIs and GMFRs from 
baseline at each time point and maximum titer or ratio at any time point, as well as the 
proportion of subjects with seroconversion, defined as a 2-fold increase in S-IgA over 
baseline or 4-fold over the minimal limit of assay detection at any time point and at each time 
point. The baseline refers to screening and Day 78 prior to boost vaccination. 

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Systemic immune responses in terms of seroconversion of IgG and IgA antibody titers (PT, 
FHA, PRN, FIM 2/3, or BPZE1 whole cell extract for IgG only) will be summarized by 
treatment arm. Analyses will include the GMTs along with corresponding 95% CIs and 
GMFR at each time point and maximum titer or ratio at any time point, as well as the 
proportion and 95% CI of subjects achieving seroconversion (defined as 2-fold increase over 
baseline or 4-fold increase over the minimum limit of detection) at any time point and at each 
time point. 
Colonization data will be summarized by treatment arm at available time points. Analysis 
will include dichotomized results (Yes/No) for B. pertussis culture along with colony counts 
from Days 92 to 113 following vaccination with BPZE1 or placebo. The effect of recent and 
post vaccination with BPZE1 on absolute colony counts and clearance of colonization will be 
assessed for this period. The analyses will include proportion of subjects with positive B. 
pertussis at Day 78 (prior to boosting vaccination) as well as Day 254 (end-of-study). 
7.7.4 
Analyses of Efficacy Endpoint 
No clinical efficacy endpoint will be collected in this study other than immunological 
response. 
7.7.5 
Analysis of Secondary Safety Endpoints 
Adverse events (eg, treatment-emergent AEs, SAEs, and SUSARs) will be coded by 
MedDRA for preferred term and system organ class. 
Serious AEs will be reported by detailed listings showing the event description, MedDRA 
preferred term and system organ class, relevant dates (study vaccinations and AEs), severity, 
relatedness, and outcome for each event. Any SAE attributed to vaccination will be classified 
as a SUSAR. Nonserious unsolicited AEs will be summarized as number and percentage of 
subjects reporting at least one event in each MedDRA preferred term and system organ class, 
and cross tabulated by severity and relationship to study product.  
Measurements of vital signs will be statistically described, and categorical severity scores of 
vital signs will be summarized in counts and percentages of subjects by treatment arm. 
Change from baseline will be expressed where applicable. 

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7.7.6 
Other Analyses 
Summary statistics will be provided for exploratory endpoints, demographics, medical 
history, study dose compliance, physical examination, social history, and risk factor variables 
at baseline. Exploratory analysis will include testing of T-cell responses using stimulated 
PBMCs for the subset of subjects at a later time point. Tetanus and diphtheria testing (per 
validated ELISA) may occur at a later date and may include only selected subsets. Future 
assays developed for BPZE1 may also utilize samples from this study for either development 
or testing at a future time. 
7.7.7 
Interim Analyses 
A SMC will be convened by ILiAD Biotechnologies to review study progress and 
participant, clinical, safety, and reactogenicity data, as described after all doses in the safety 
lead-in cohort complete Day 8 following first (prime) vaccination to allow the remainder of 
the subjects to be randomized. The SMC safety review must include at minimum 
demographic information, clinical laboratory values (with toxicity grading), dosing 
compliance, reactogenicity (with toxicity grading), and AE/SAEs (graded and attributed). 
Additional data may be requested by the SMC, and an interim statistical report may be 
generated as deemed necessary and appropriate by ILiAD Biotechnologies. The SMC may 
receive data in aggregate and presented by treatment arm, including expected and observed 
rates of the expected AEs. The SMC will review grouped data in the closed session only. The 
SMC will meet and review these data at scheduled time points or ad hoc as needed during 
this trial as defined in the SMC charter. As an outcome of any meeting (after the safety 
lead-in cohort or with a safety pause), the SMC will make a recommendation as to the 
advisability of proceeding with study vaccinations (as applicable), and to continue, modify, 
or terminate this trial. The SMC will be provided with an executive summary of safety and 
immunogenicity results (graphic and written) for the overall study. 

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8 
Data Quality Assurance 
The sponsor will perform quality control and assurance checks on all clinical studies that it 
sponsors. Before enrolling any subjects in this study, sponsor personnel and the investigator 
will review the protocol, the package inserts, investigator brochures, the eCRFs and 
instructions for their completion, the procedure for obtaining informed consent, and the 
procedure for reporting AEs and SAEs. A qualified representative of the sponsor will monitor 
the conduct of the study by visiting the site and by contacting the site by telephone and 
e-mail. During these site visits, information recorded in the eCRFs will be verified against 
source documents. 
8.1 
Data Management 
As part of the responsibilities assumed by participating in the study, the investigator agrees to 
maintain adequate case histories for the subjects treated as part of the research under this 
protocol. The investigator agrees to maintain accurate eCRFs and source documentation as 
part of the case histories. These source documents may include laboratory reports and subject 
diaries for reactogenicity reporting. 
Study site staff will enter subject data into a FDA-approved and auditable data management 
system. The analysis data populations will be a combination of these data and data from other 
sources (eg, laboratory data). 
Clinical data management will be performed in accordance with applicable PPD and/or 
ILiAD standards and data cleaning procedures to ensure the integrity of the data, eg, 
removing errors and inconsistencies in the data. Adverse event terms (including SAEs) will 
be coded using the MedDRA, an internal validated medical dictionary, and concomitant 
medications will be coded using the WHO Drug Dictionary. 
After final database lock, each clinical site will receive a compact disc read-only memory 
(CDROM) containing all of their site-specific eCRF data as entered into an FDA-approved 
and auditable data management system for the study, including full discrepancy and audit 
history. Additionally, a CDROM copy of all of the study site’s data from the study will be 
created and sent to the sponsor for storage. The CRO will maintain a duplicate CDROM copy 
for their records. In all cases, subject initials will not be collected or transmitted to the 
sponsor. 

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9 
Ethics 
9.1 
Institutional Review Board 
Federal regulations and the International Council for Harmonisation (ICH) guidelines require 
that approval be obtained from an IRB before participation of human subjects in research 
studies. Before study onset, the protocol, informed consent, advertisements to be used for the 
recruitment of study subjects, and any other written information regarding this study to be 
provided to the subject or the subject’s legal guardian must be approved by the IRB. 
Documentation of all IRB approvals and of the IRB compliance with ICH harmonised 
tripartite guideline E6(R2): Good Clinical Practice (GCP) will be maintained by the site and 
will be available for review by the sponsor or its designee. 
All IRB approvals should be signed by the IRB chairman or designee and must identify the 
IRB name and address, the clinical protocol by title or protocol number or both, and the date 
approval or a favorable opinion was granted. 
The investigator is responsible for providing written summaries of the progress and status of 
the study at intervals not exceeding 1 year or otherwise specified by the IRB. The 
investigator must promptly supply the sponsor or its designee, the IRB, and, where 
applicable, the institution, with written reports on any changes significantly affecting the 
conduct of the study or increasing the risk to subjects. 
9.2 
Ethical Conduct of the Study 
The study will be performed in accordance with the ethical principles that have their origin in 
the Declaration of Helsinki, ICH GCP, the protocol, and all applicable regulations. 
9.3 
Subject Information and Consent 
A written informed consent in compliance with regulatory authority regulations US Title 21 
Code of Federal Regulations (CFR) Part 50 shall be obtained from each subject before 
entering the study or performing any unusual or nonroutine procedure that involves risk to 
the subject. An informed consent template may be provided by the sponsor to investigative 
sites. If any institution-specific modifications to study-related procedures are proposed or 
made by the site, the consent should be reviewed by the sponsor or its designee or both 
before IRB submission. Once reviewed, the consent will be submitted by the investigator to 

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his or her IRB for review and approval before the start of the study. If the ICF is revised 
during the course of the study, all active participating subjects must sign the revised form. 
Before recruitment and enrollment, each prospective subject or his or her legal guardian will 
be given a full explanation of the study and be allowed to read the approved ICF. Once the 
investigator is assured that the subject/legal guardian understands the implications of 
participating in the study, the subject/legal guardian will be asked to give consent to 
participate in the study by signing the ICF.  
The investigator shall retain the signed original ICF and give a copy of the signed original 
form to the subject or legal guardian. 
Subjects will also be asked to provide a signed informed consent for the use of samples for 
further pertussis-specific testing or assay development. 

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10 Investigator’s Obligations 
The following administrative items are meant to guide the investigator in the conduct of the 
study but may be subject to change based on industry and government standard operating 
procedures, working practice documents, or guidelines. Changes will be reported to the IRB 
but will not result in protocol amendments. 
10.1 Confidentiality 
All laboratory specimens, evaluation forms, reports, and other records will be identified in a 
manner designed to maintain subject confidentiality. All records will be kept in a secure 
storage area with limited access. Clinical information will not be released without the written 
permission of the subject (or the subject’s legal guardian), except as necessary for monitoring 
and auditing by the sponsor, its designee, the FDA, or the IRB. 
The investigator and all employees and coworkers involved with this study may not disclose 
or use for any purpose other than performance of the study any data, record, or other 
unpublished, confidential information disclosed to those individuals for the purpose of the 
study. Prior written agreement from the sponsor or its designee must be obtained for the 
disclosure of any said confidential information to other parties. 
10.2 Financial Disclosure and Obligations 
Investigators and subinvestigators are required to provide financial disclosure information to 
allow the sponsor to submit the complete and accurate certification or disclosure statements 
required under 21 CFR 54. In addition, the investigator and subinvestigator must provide to 
the sponsor a commitment to promptly update this information if any relevant changes occur 
during the course of the investigation and for 1 year following the completion of the study. 
Neither the sponsor nor the CRO is financially responsible for further testing or treatment of 
any medical condition that may be detected during the screening process. In addition, in the 
absence of specific arrangements, neither the sponsor nor the CRO is financially responsible 
for further treatment of the subject’s disease. 

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10.3 Investigator Documentation 
Prior to beginning the study, the investigator will be asked to comply with ICH E6(R2) 
8.2 and Title 21 of the CFR by providing the following essential documents, including but 
not limited to: 
 IRB approval 
 Original investigator-signed investigator agreement page of the protocol 
 Form FDA 1572, fully executed, and all updates on a new fully executed Form 
FDA 1572 
 Current (within 2 years) curriculum vitae for the investigator and each subinvestigator 
listed on Form FDA 1572 
 Financial disclosure information to allow the sponsor to submit complete and accurate 
certification or disclosure statements required under 21 CFR 54. In addition, the 
investigators must provide to the sponsor a commitment to promptly update this 
information if any relevant changes occur during the course of the investigation and for 
1 year after the completion of the study. 
 Executed clinical study agreement 
 Documentation of Federal Wide Assurance number and expiration date 
 IRB-approved informed consent, samples of site advertisements for recruitment for this 
study, and any other written information regarding this study that is to be provided to the 
subject or legal guardian 
 Site delegation log 
 Documentation of human subjects’ protection training by all staff listed on the site 
delegation log 
 Laboratory certifications and normal ranges for any local laboratories used by the site, in 
accordance with 42 CFR 493 
 Centers for Laboratory Improvement Amendments waived on site urine pregnancy test 

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10.4 Study Conduct 
The investigator agrees that the study will be conducted according to the principles of ICH 
E6(R2) and 21 CFR 312. The investigator will conduct all aspects of this study in accordance 
with all national, state, and local laws or regulations. Study information from this protocol 
will be posted on publicly available clinical trial registers before enrollment of subjects 
begins. 
10.5 Adherence to Protocol 
The investigator agrees to conduct the study as outlined in this protocol in accordance with 
ICH E6(R2) and 21 CFR 312 and all applicable guidelines and regulations. 
10.6 Adverse Events and Study Report Requirements 
By participating in this study, the investigator agrees to submit reports of SAEs according to 
the time line and method outlined in the protocol. In addition, the investigator agrees to 
submit annual reports to the study site IRB as appropriate. 
10.7 Investigator’s Final Report 
Upon completion of the study, the investigator, where applicable, should inform the 
institution; the investigator/institution should provide the IRB with a summary of the study’s 
outcome and the sponsor and regulatory authority(ies) with any reports required. 
10.8 Records Retention 
Essential documents should be retained until at least 2 years after the last approval of a 
marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product, as described in 
21 CFR 312.62. These documents should be retained for a longer period, however, if required 
by the applicable regulatory requirements or by an agreement with the sponsor. It is the 
responsibility of the sponsor to inform the investigator/institution as to when these 
documents no longer need to be retained. 

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10.9 Publications 
After completion of the study, the data may be considered for reporting at a scientific 
meeting or for publication in a scientific journal. In these cases, the sponsor will be 
responsible for these activities to determine how the manuscript is written and edited, the 
number and order of authors, the publication to which it will be submitted, and other related 
issues. The sponsor has final approval authority over all such issues. 
Data are the property of the sponsor and cannot be published without prior authorization 
from the sponsor, but data and publication thereof will not be unduly withheld. 

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11 Study Management 
The administrative structure will include an unblinded biostatistics team (statisticians and 
programmers). 
11.1 Monitoring 
11.1.1 
External Data Monitoring Committee 
11.1.1.1 
Safety Monitoring Committee 
Safety oversight will be conducted by a SMC that is an independent group of experts that 
monitors subject safety and advises ILiAD Biotechnologies. The SMC members will be 
separate and independent of study personnel participating in this study and should not have 
scientific, financial, or other conflict of interest related to this study. The SMC will consist of 
members with appropriate expertise to contribute to the interpretation of the data from this 
study. 
The SMC will review study progress and participant, clinical, safety, and reactogenicity data 
at the following time points: 
 After the subjects in the entire safety lead-in cohort (both dose levels) have completed 
Day 8 (Visit 2). The SMC will review all safety data through Day 8 (reactogenicity 
and safety laboratory results) and any AEs which have occurred since study initiation. 
 Ad hoc when a halting rule is met, for immediate concerns regarding observations 
during this study, or as needed. 
The SMC will operate under the rules of an ILiAD Biotechnologies-approved charter that 
will be approved at the organizational meeting of the SMC. At this time, each data element 
that the SMC needs to assess will be clearly defined. Procedures for SMC reviews/meetings 
will be defined in the charter. The SMC will review applicable data to include, but not 
limited to, study progress and participant, clinical, safety, and reactogenicity data. Reports 
may include enrollment and demographic information, medical history, concomitant 
medications, physical assessments, and solicited and unsolicited AE/SAEs. Additional data 
may be requested by the SMC, and interim statistical reports may be generated as deemed 
necessary and appropriate by ILiAD Biotechnologies. The SMC may receive data in 

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aggregate and presented by treatment arm. The SMC may also be provided with expected and 
observed rates of the expected AEs in an unblinded fashion and may request the treatment 
assignment be unblinded for an individual subject if required for safety assessment.  
The SMC will review grouped and unblinded data in the closed session only. The SMC will 
meet and review these data at scheduled time points or ad hoc as needed during this study as 
defined in the SMC charter. As an outcome of each review/meeting, the SMC will make a 
recommendation as to the advisability of proceeding with study vaccinations (as applicable), 
and to continue, modify, or terminate this study. 
ILiAD Biotechnologies or the SMC chair may convene the SMC on an ad hoc basis 
according to protocol criteria or if there are immediate concerns regarding observations 
during the course of the study. The ILiAD Biotechnologies medical monitor is empowered to 
stop enrollment and study vaccinations if AEs that meet the halting criteria are reported. The 
ILiAD Biotechnologies/CRO assigned medical monitor will be responsible for reviewing 
SAEs in real time. The SMC will review SAEs on a regular basis and ad hoc during the 
study. 
11.1.2 
Monitoring of the Study 
The clinical monitor, as a representative of the sponsor, has the obligation to follow the study 
closely. In doing so, the monitor will visit the investigator and study site at periodic intervals, 
in addition to maintaining necessary telephone and letter contact. The monitor will maintain 
current personal knowledge of the study through observation, review of study records and 
source documentation, and discussion of the conduct of the study with the investigator and 
personnel. 
All aspects of the study will be carefully monitored, by the sponsor or its designee, for 
compliance with applicable government regulation with respect to current GCP and current 
standard operating procedures. 
11.1.3 
Inspection of Records 
Investigators and institutions involved in the study will permit study-related monitoring, 
audits, IRB review, and regulatory inspections by providing direct access to all study records. 

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In the event of an audit, the investigator agrees to allow the sponsor, representatives of the 
sponsor, or a regulatory agency (eg, FDA) access to all study records. 
The investigator should promptly notify the sponsor and the CRO of any audits scheduled by 
any regulatory authorities and promptly forward copies of any audit reports received to the 
sponsor. 
11.2 Management of Protocol Amendments and Deviations 
11.2.1 
Modification of the Protocol 
Any changes in this research activity, except those necessary to remove an apparent, 
immediate hazard to the subject, must be reviewed and approved by the sponsor or its 
designee. Amendments to the protocol must be approved by the IRB before subjects can be 
enrolled into an amended protocol. Letters of amendment or clarification do not need to be 
approved by the IRB. 
11.2.2 
Protocol Deviations 
The investigator or designee must document and explain in the subject’s source 
documentation any deviation from the approved protocol. The investigator may implement a 
deviation from, or a change of, the protocol to eliminate an immediate hazard to study 
subjects without prior IRB approval. As soon as possible after such an occurrence, the 
implemented deviation or change, the reasons for it, and any proposed protocol amendments 
should be submitted to the IRB for review and approval, to the sponsor for agreement, and to 
the regulatory authorities, if required. 
A deviation from the protocol is an unintended or unanticipated departure from the 
procedures or processes approved by the sponsor and the IRB and agreed to by the 
investigator. A significant deviation occurs when there is nonadherence to the protocol by the 
subject or investigator that results in a significant, additional risk to the subject. Significant 
deviations can include nonadherence to inclusion or exclusion criteria, or nonadherence to 
FDA regulations or ICH GCP guidelines, and will lead to the subject being withdrawn from 
the study (Section 4.2). 
Protocol deviations will be documented by the clinical monitor throughout the course of 
monitoring visits. Investigators will be notified in writing by the monitor of deviations. The 

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IRB should be notified of all significant protocol deviations in a timely manner, as defined by 
the IRB. 
11.3 Study Termination 
Although ILiAD Biotechnologies has every intention of completing the study, ILiAD 
Biotechnologies reserves the right to discontinue the study at any time for clinical or 
administrative reasons. 
The end of the study is defined as the date on which the last subject completes Visit 9 
(end-of-study visit) (Table 13-1). 
11.4 Final Report 
Whether the study is completed or prematurely terminated, the sponsor will ensure that the 
CSRs are prepared and provided to the regulatory agency(ies) as required by the applicable 
regulatory requirement(s). The sponsor will also ensure that the CSRs in marketing 
applications meet the standards of the ICH harmonised tripartite guideline E3: Structure and 
content of CSRs.  
The primary database lock will occur at Day 113, and all data collected through Day 113 will 
be included in the CSR and submitted to regulatory authorities. A subsequent longer-term 
safety follow-up, including longer-term persistence of immune responses, will occur through 
Day 254. These data will be provided, following a second database lock, in an addendum to 
the CSR. Subjects will return to the clinical site on Day 254 (±15 days) for end-of-study 
procedures. 
Where required by applicable regulatory requirements, an investigator signatory will be 
identified for the approval of the CSR. The investigator will be provided reasonable access to 
statistical tables, figures, and relevant reports and will have the opportunity to review the 
complete study results. 
Upon completion of the CSR, the sponsor will provide the investigator with the full summary 
of the study results. The investigator is encouraged to share the summary results with the 
study subjects, as appropriate. The study results will be posted on publicly available clinical 
trial registers. 

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12 Reference List 
Althouse BM, Scarpino SV. Asymptomatic transmission and the resurgence of Bordetella 
pertussis. BMC Med. 2015;13:146. 
Department of Health and Human Services (DHHS), Food and Drug Administration, Center 
for Biologics Evaluation and Research (US). Guidance for industry: Toxicity grading for 
healthy adult and adolescent volunteers enrolled in preventive vaccine clinical trials. 
September 2007 [cited 2017 Nov 29]. Available from: https://www.gpo.gov/fdsys/pkg/FR-
2007-09-27/pdf/E7-19155.pdf 
Division of AIDS (DAIDS), National Institute of Allergy and Infectious Diseases, National 
Institutes of Health, US Department of Health and Human Services. Division of AIDS 
(DAIDS) table for grading the severity of adult and pediatric adverse events. July 2017 [cited 
2019 May 10]. Available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf 
Feunou PF, Ismaili J, Debrie AS, et al. Genetic stability of the live attenuated Bordetella 
pertussis vaccine candidate BPZE1. Vaccine. 2008;26(45):5722-7. 
Feunou PF, Mielcarek N, Locht C. Reciprocal interference of maternal and infant 
immunization in protection against pertussis. Vaccine. 2016;34(8):1062-9. 
Headache classification committee of the international headache society (IHS), The 
international classification of headache disorders (ICHD-3), 3rd edition. Cephalalgia. 
2018;38(1):1-211. 
ILiAD Biotechnologies. BPZE1. Investigator’s brochure, 0.42 ed. Weston (FL); 2017. 44 p. 
Locht C, Papin JF, Lecher S, et al. Live attenuated pertussis vaccine BPZE1 protects baboons 
against Bordetella pertussis disease and infection. J Infect Dis. 2017;216(1):117-24. 
Mielcarek N, Debrie AS, Maheiux S, et al. Dose response of attenuated Bordetella pertussis 
BPZE1-induced protection in mice. Clin Vaccine Immunol. 2010;17(3):317-24. 
Mielcarek N, Debrie AS, Raze D, et al. Live attenuated B. pertussis as a single-dose nasal 
vaccine against whooping cough. PLoS Pathog. 2006;2(7):e65. 

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National Asthma Education and Prevention Program Expert Panel Report 3 (EPR-3), 
National Institutes of Health, US Department of Health and Human Services, National Heart, 
Lung, and Blood Institute. Guidelines for the diagnosis and management of asthma. October 
2007 [cited 2019 May 10]. Available from: 
https://www.nhlbi.nih.gov/files/docs/guidelines/asthsumm.pdf 
Skerry CM, Cassidy JP, English K, et al. A live attenuated Bordetella pertussis candidate 
vaccine does not cause disseminating infection in gamma interferon receptor knockout mice. 
Clin Vaccine Immunol. 2009;16(9):1344-51. 
Warfel JM, Zimmerman LI, Merkel TJ. Acellular pertussis vaccines protect against disease 
but fail to prevent infection and transmission in a nonhuman primate model. Proc Natl Acad 
Sci USA. 2014;111(2):787-92. 
Wearing HJ, Rohani P. Estimating the duration of pertussis immunity using epidemiological 
signatures. PLoS Pathog. 2009;5(10):e1000647. 
Yeung KHT, Duclos P, Nelson EAS, et al. An update of the global burden of pertussis in 
children younger than 5 years: a modelling study. Lancet Infect Dis. 2017;17(9):974-80. 

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13 Appendices 
13.1 Appendix: Schedule of Events 
 

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Table 13-1 
Schedule of Events 
Procedure 
Screening 
Treatment Period 
Study visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10a 
Days relative to most recent vaccination 
–30 to 0 
1 
8 
29 
78 
85/1 
8 
12 
29 
85 
169 
Days relative to first vaccinationb 
–30 to 0 
1 
8 
29 
78 
85 
92 
96 
113 
169 
254 
Window allowance 
30 
0 
+3 
+7 
-7 
+10 
+2 
+/-2 
+7 
-7 
±15 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X c 
 
 
 
X c 
 
 
 
 
 
Demographic and baseline data d 
X 
 
 
 
 
 
 
 
 
 
 
Medical history e 
X 
X c 
 
 
 
X c 
 
 
 
 
 
Medication f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Xg 
X g 
Serology h 
X 
 
 
 
 
 
 
 
 
 
 
Urine drug screen 
X 
 
 
 
 
 
 
 
 
 
 
Physical examination i 
X 
X j 
X 
X 
 
X j 
X 
X 
X 
 
 
Vital sign measurements 
X 
X k 
X 
X 
 
X k 
X 
X 
X 
 
 
Safety laboratory tests for enrollment l 
X 
 
 
 
 
 
 
 
 
 
 
Safety laboratory tests for safety cohort m 
X 
 
X 
 
 
X n 
X 
 
 
 
 
Urine pregnancy test (female subjects of childbearing 
potential) 
X 
X n 
 
 
 
X n 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
Vaccination o 
 
X 
 
 
 
X 
 
 
 
 
 
Subject diary dispensing p 
 
X 
 
 
 
X 
 
 
 
 
 
Subject diary reviewed q 
 
 
X 
 
 
 
X 
 
 
 
 
Reactogenicity - post-vaccination 
 
X r 
X s 
 
 
X r 
X s 
 
 
 
 

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Procedure 
Screening 
Treatment Period 
Study visit 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10a 
Days relative to most recent vaccination 
–30 to 0 
1 
8 
29 
78 
85/1 
8 
12 
29 
85 
169 
Days relative to first vaccinationb 
–30 to 0 
1 
8 
29 
78 
85 
92 
96 
113 
169 
254 
Window allowance 
30 
0 
+3 
+7 
-7 
+10 
+2 
+/-2 
+7 
-7 
±15 
Immunogenicity laboratory tests for serum pertussis 
IgG and IgA ELISA 
 
X n 
 
X 
 
X n 
 
 
X 
X 
X 
Mucosal pertussis nasal antibody testing (S-IgA 
ELISA) – nasal absorption device t 
X u 
 
 
X 
X 
 
 
 
X 
X 
X 
Nasal collection for B. pertussis colonization 
 
 
 
 
X v 
 
X 
X 
X v 
 
Xw 
PBMC for cellular immunity (subset of no more than 
60 subjects)  
 
X 
X 
 
 
 
X 
 
 
 
 
Collection of serious adverse events and adverse 
events of special interest only  x 
 
 
 
 
 
 
 
 
 
X 
X 
Adverse events x y 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
End-of-study form completion  
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations: ELISA, enzyme-linked immunosorbent assay; Ig, immunoglobulin; PBMC, peripheral blood mononuclear cell; S-IgA, secretory 
immunoglobulin A. 
a 
End-of-study Visit. 
b 
Days relative to vaccination are only estimates as the window allowance is not inclusive. Should a study pause occur than visits/windows will be adjusted to 
allow for subjects to continue without protocol deviation. Visit schedule following the boosting vaccination is calculated relative to the day the boosting 
vaccination was received. 
c 
Inclusion/exclusion criteria and medical history will be reviewed and updated on Day 1 and Day 85 with specific vaccination exclusions applied.  
d 
Including date of birth (day, month, and year), sex, race, ethnicity, weight, height, and body mass index (derived). 
e 
Including prior and concomitant medical conditions, surgeries, and significant procedures. 
f 
Concomitant medications include all medications (including vaccines) taken by the subject from the time of signing the informed consent through 28 days 
after the boosting vaccination (or through early termination visit if prior to that time).  
g 
Only medications associated with serious adverse events. 
h 
Serology testing will include hepatitis B, hepatitis C, and human immunodeficiency virus.  

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i 
Full physical examination at screening; symptom-directed (targeted) physical examination at all other scheduled time points. Interim physical examinations 
will be performed at the discretion of the investigator, if necessary. Height and weight will be measured at screening only.  
j 
On Day 1 (Visit 1) and 85 (Visit 5), targeted symptom-directed physical examination will be performed before vaccine administration. 
k 
On Day 1 (Visit 1) and 85 (Visit 5), vital sign measurements will be collected once before vaccine administration and at 60 minutes (±15 minutes) after 
vaccine administration (before subjects are discharged). 
l 
Safety laboratory testing for safety cohort include (Table 13-2) hemoglobin, white blood count with differential, platelet count, sodium, potassium, random 
glucose, blood urea nitrogen, creatinine, calcium, albumin, total protein, bilirubin, alanine aminotransferase, aspartate aminotransferase, prothrombin time, 
and partial thromboplastin time. See Table 13-2 for specific laboratory tests to utilize for exclusion for the full cohort (kidney, hepatic, and 
hematology/coagulation only). Laboratory testing may be repeated once during the 30-day screening period if specific values used for exclusion criteria 
exceed toxicity Grade 1, with the last value being the value of record. 
m 
The first 48 subjects randomly assigned will be designated the safety lead-in cohort and safety laboratory testing will be performed in this subset beyond the 
screening visit. Should any laboratory value result in a grade 3 or greater toxicity score this lab must be entered as an adverse event and followed with 
retesting and observing for resolution or new clinical baseline 
n 
Performed prior to vaccination.  
 
Subjects will be randomly assigned as per Table 3-1. 
p 
All subjects will record reactogenicity in the daily subject diary starting on the same day of the prime (Day 1) and boosting (Day 85) vaccinations and 
for additional days (not counting vaccination day). 
q 
The clinical staff will review the information from the subject diary with the subjects on Days 8 and 92. Toxicity grading will be applied by investigator for 
all subject recorded reactogenicity on Days 1 through 8. Should any reactogenicity event extend beyond 7 days post vaccination and be clinically significant 
by toxicity grade 1 or greater, then it will be entered as an AE with the same start date as the reactogenicity event and followed to resolution. 
r 
Reactogenicity will be collected on Day 1 (Visit 1) and 85 (Visit 5) at 60 minutes (±15 minutes) after dose administration (before subjects are discharged). 
s 
To be collected from day of vaccination through additional 7 days post-vaccination by subject. 
t 
Must occur at least 6 days prior to intranasal vaccination. If a subject fails to return for Day 78 (Visit 4) than nasal sampling for colonization should occur on 
Day 85 (Visit 5) AFTER mucosal sampling has been performed but PRIOR to nasal vaccination (and there must be a 60 minute window between nasal 
aspiration and vaccination). 
u 
Collected but only tested within the trial if the subject is randomly assigned into the study. Samples may be used per subject consenting for additional 
product development needs. 
v 
To be collected after mucosal pertussis nasal antibody collection. 
w 
Only in subjects who tested positive by pertussis culture at Day 113. Any subject who remains positive to pertussis on Day 254 will be provided a short 
course of azithromycin. Should a subject be allergic to azithromycin, an appropriate antibiotic will be substituted that has effectiveness against B. pertussis. 
x 
At the discretion of the investigator a urine drug screen may be performed on any subject who experiences an adverse event. 
y 
All adverse events will be collected 28 days after each vaccination. Adverse events related to vaccination will be collected through Day 113.

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13.2 Appendix: FDA Table for Laboratory Grading 
Table 13-2 
Laboratory Abnormalities 
Seruma 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially Life 
Threatening 
(Grade 4)b 
Sodium – hyponatremia (mEq/L)  
132-134 
130-131 
125-129 
< 125 
Sodium – hypernatremia (mEq/L) 
144-145 
146-147 
148-150 
> 150 
Potassium – hyperkalemia 
(mEq/L) 
5.1-5.2 
5.3-5.4 
5.5-5.6 
> 5.6 
Potassium – hypokalemia 
(mEq/L) 
3.5-3.6 
3.3-3.4 
3.1-3.2 
< 3.1 
Glucose – hyperglycemia  
Random (mg/dL)  
 
110-125 
 
126-200 
 
> 200 
Insulin 
requirements or 
hyperosmolar 
coma 
Blood Urea Nitrogen (mg/dL)  
23-26 
27-31 
> 31 
Requires 
dialysis 
Creatinine (mg/dL)* 
1.5-1.7 
1.8-2.0 
2.1-2.5 
> 2.5 or requires 
dialysis 
Calcium – hypocalcemia (mg/dL) 
8.0-8.4 
7.5-7.9 
7.0-7.4 
< 7.0 
Calcium – hypercalcemia (mg/dL) 
10.5-11.0 
11.1-11.5 
11.6-12.0 
> 12.0 
Albumin – hypoalbuminemia 
(g/dL)  
2.8-3.1 
2.5-2.7 
< 2.5 
-- 
Total Protein – hypoproteinemia 
(g/dL)  
5.5-6.0 
5.0-5.4 
<5.0 
-- 
Liver Function Tests – ALT, AST 
increase by factor* 
1.1-2.5 × ULN 
2.6-5.0 × ULN 
5.1-10 × ULN 
> 10 × ULN 
Bilirubin – when accompanied by 
any increase in liver function test 
increase by factor* 
1.1-1.25 × ULN 
1.26-1.5 × ULN 
1.51-1.75 × ULN 
> 1.75 × ULN 
Bilirubin – when liver function 
test is normal; increase by factor* 
1.1-1.5 × ULN 
1.6-2.0 × ULN 
2.0-3.0 × ULN 
> 3.0 × ULN 
Hematologya 
Mild (Grade 1) 
Moderate 
(Grade 2) 
Severe (Grade 3) 
Potentially Life 
Threatening 
(Grade 4)b 
Hemoglobin (Female) (gm/dL)* 
11.0-12.0 
9.5-10.9 
8.0-9.4 
< 8.0 
Hemoglobin (Female) change 
from baseline value (gm/dL) 
Any 
decrease - 1.5 
1.6-2.0 
2.1-5.0 
> 5.0 
Hemoglobin (Male) (gm/dL)* 
12.5-13.5 
10.5-12.4 
8.5-10.4 
< 8.5 

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Hemoglobin (Male) change from 
baseline value (gm/dL) 
Any 
decrease - 1.5 
1.6-2.0 
2.1-5.0 
> 5.0 
WBC Increase (cell/mm3)* 
10,800-15,000 
15,001-20,000 
20,001-25,000 
> 25,000 
WBC Decrease (cell/mm3)* 
2,500-3,500 
1,500-2,499 
1,000-1,499 
< 1,000 
Platelets Decreased - cell/mm
3* 
125,000 – 
140,000 
100,000 – 
124,000 
25,000 – 99,000 
< 25,000 
Prothrombin time – increase by 
factor* 
1.0-1.10 × ULN 
1.11-1.20 × 
ULN 
1.21-1.25 × ULN 
> 1.25 × ULN 
partial thromboplastin time – 
increase by factor * 
1.0-1.2 × ULN 
1.21-1.4 × ULN 
1.41-1.5 × ULN 
> 1.5 × ULN 
Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; ULN, upper limit of normal; 
WBC, white blood cell. 
*Screening labs with toxicity scores greater than 1 are exclusion criteria for the full cohort only (greyed line 
items).  
All safety labs listed in Table 13-2 with a toxicity score greater than 1 are exclusion criteria for the safety 
cohort. 
a 
The laboratory values provided in the tables serve as guidelines and are dependent upon institutional 
normal parameters. Institutional normal reference ranges should be provided to demonstrate that they are 
appropriate.  
b 
The clinical signs or symptoms associated with laboratory abnormalities might result in characterization of 
the laboratory abnormalities as Potentially Life Threatening (Grade 4). For example, a low sodium value 
that falls within a grade 3 parameter (125-129 mE/L) should be recorded as a grade 4 hyponatremia event if 
the subject had a new seizure associated with the low sodium value. 
Source: DHHS 2007 
 
 

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13.3 Appendix: FDA Table for Vital Sign Grading 
Table 13-3 
Vital Sign Abnormality 
Vital Signsa  
Mild 
(Grade 1)  
Moderate 
(Grade 2)  
Severe 
(Grade 3)  
Potentially Life  
Threatening  
(Grade 4) 
Fever (°F)b 
100.4 – 101.1 
101.2 – 102.0  
102.1 – 104  
>104  
Tachycardia (beats per 
minute) 
101 – 115  
116 – 130  
>130  
Emergency room visit or  
hospitalization for arrhythmia
Bradycardia (beats per  
minute)c
50 – 54  
45 – 49  
<45  
ER visit or hospitalization for  
arrhythmia
Hypertension (systolic)  
(mm Hg) 
141 – 150  
151 – 155  
>155  
ER visit or hospitalization for  
malignant hypertension 
Hypertension (diastolic) 
(mm Hg)  
91 – 95  
96 – 100  
>100  
ER visit or hospitalization for  
malignant hypertension  
Hypotension (systolic)  
(mm Hg) 
85 – 89  
80 – 84  
<80  
ER visit or hospitalization for 
hypotensive shock
Note: Grade 0 will be the classification if the observation is less than a Grade 1. Respiratory rate was removed 
from the FDA table for vital sign grading as this is not a parameter being measured in this study. 
a. 
Subject should be at rest for all vital sign measurements.  
b. 
Oral temperature; no recent hot or cold beverages or smoking.  
c. 
When resting heart rate is between 60 to 100 beats per minute. Use clinical judgement when characterizing 
bradycardia among some healthy subject populations, for example, conditioned athletes. 
Source: DHHS 2007.