Bordetella Pertussis, Whooping Cough
Conditions
Keywords
Bordetella pertussis (B. pertussis), Whooping Cough, BPZE1, Boostrix, Vaccine, Children, Booster, Live attenuated vaccine
Brief summary
This study evaluates the safety and immunogenicity of the BPZE1 live, attenuated pertussis vaccine, intended to prevent nasopharyngeal colonization and pertussis disease, and compares BPZE1 vaccine vs Boostrix vaccine vs both BPZE1 and Boostrix vaccines. This is a multi-center, randomized, placebo- and active-comparator-controlled study in healthy, school-age children with a 6-month safety follow-up after the first vaccination.
Detailed description
This multi-center, randomized, placebo- and active-comparator-controlled study evaluates the safety and immunogenicity of the BPZE1 live attenuated pertussis vaccine, intended to prevent nasopharyngeal colonization and pertussis disease. Healthy school-age children will be randomly assigned to 1 of 3 different study treatment groups to receive the intranasal BPZE1 vaccine, the intramuscular Boostrix vaccine, or both. Subjects will first receive the intranasal vaccine (BPZE1 or placebo) using a small, cone-shaped device that attaches to a syringe and sprays the vaccine into the nose. After a 10-minute waiting period, subjects will receive the intramuscular vaccine (Boostrix or placebo) in the upper arm. As this is the first study in school-age children, a staggered enrollment is planned with the first 45 subjects in the older age group of 11-17 years designated as the safety lead-in cohort. After reactogenicity results from the first 7 days after vaccination of the safety lead-in cohort are reviewed by the safety monitoring committee, the remainder of the subjects will be enrolled. Subjects who choose to take part in a small sub-study of revaccination/attenuated challenge will receive BPZE1 intranasal vaccine (open-label) 3 months after the first vaccination. Safety will be monitored for 6 months after the first vaccination.
Interventions
BIOLOGICALBPZE1 pertussis vaccine and placebo
Live attenuated pertussis vaccine and placebo
BIOLOGICALBPZE1 pertussis vaccine and Boostrix
Live attenuated pertussis vaccine and tetanus, diphtheria, and aP vaccine
BIOLOGICALPlacebo and Boostrix
Tetanus, diphtheria, and aP vaccine and placebo
Sponsors
ILiAD Biotechnologies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Male or female subject 6 to 17 years of age on Day 1. 2. Subject must provide informed consent (assent, depending on age) prior to participation in study and comply with protocol requirements. 3. If female, the subject is not pregnant or lactating. If female of childbearing potential, the subject must agree to either be heterosexually inactive or follow birth control methods per protocol from at least 21 days prior to enrollment and through 90 days following any study vaccination. 4. Subject has a stable health status, as established by physical examination, vital sign measurements, and medical history. 5. Subject (and/or legal guardian) has access to a consistent and reliable means of electronic or telephone contact, which may be in the home, workplace, school, or by personal mobile electronic device. 6. Subject is willing to refrain from routine nasal sprays (including steroid sprays) or washes for at least 7 days following any study vaccination. Key
Exclusion criteria
1. The subject has a history of whole-cell pertussis vaccination in lifetime, acellular pertussis-containing vaccination (inclusive of school vaccination programs) within 3 years prior to Day 1, documented B. pertussis infection within 3 years prior to Day 1, or a history of Td-containing vaccination (without pertussis vaccine component) within 1 month prior to Day 1. 2. Chronic significant illness actively being treated or a history of recent intervention for worsening or fluctuating symptoms (at the discretion of the investigator). 3. History of cancer (malignancy). 4. Congenital, hereditary, or acquired disease or disorder classified as autoimmune, immunodeficient, coagulopathy, hepatic, renal, neurologic, or cognitive. 5. Currently uses smoking products (including vaping and e-cigarettes) and is unwilling to refrain from use from Day 1 through Day 29 following study vaccination. 6. Subject received immunoglobulin, blood-derived products, systemic corticosteroids (at a dose of \>10 mg per day for more than 10 days), or other immunosuppressant drugs within 90 days of Day 1. 7. Chronic pulmonary disease requiring active medication or pulmonary therapies except exercise-induced bronchospasm, if currently well controlled, and willing to refrain from intense exercise for 7 days following study vaccination, or intermittent asthma classification who have not had an exacerbation requiring oral systemic corticosteroids in the past year; have an forced expiratory volume (FEV1) documented to be \>80%; do not have restrictions in normal activity due to breathing issues; and have used a short-acting beta-agonist less than or equal to 2 days per week over the past 2 months. 8. History of oro/nasopharynx surgery (eg, adenoidectomy, tonsillectomy) within 60 days prior to Day 1. 9. Known hypersensitivity to latex or any component of any study vaccine. Specific to Boostrix: hypersensitivity to neomycin or polymyxin; hypersensitivity after previous administration of diphtheria, tetanus, or pertussis vaccines; or has experienced transient thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or tetanus. 10. Subject has routine and/or repeated contact with, or is currently living in a household with, an immunocompromised individual. 11. Subject resides in a residence where an infant less than 6 months of age resides or may reside.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29 | Day 29 | Geometric mean fold rise (GMFR) of mucosal S-IgA against whole cell extract (WCE) by treatment arm (BPZE1, BPZE1 + Boostrix) at Day 29. |
| Safety: Solicited Adverse Events (AEs) | Through 7 days following first study vaccination. | Solicited AEs (local injection site, nasal/respiratory, and systemic reactogenicity events) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mucosal Immunogenicity S-IgA GMR | Baseline, Day 29 | Induction of normalized S-IgA against WCE, PT, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development (fimbriae serotype 2 and 3; FIM 2/3) using GMR |
| Mucosal Immunogenicity S-IgA GMFR | Day 29 | Induction of normalized S-IgA against WCE, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development (FIM 2/3) using GMFR |
| Serum Immunogenicity IgA and IgG GMC | Baseline, Day 29 | Induction of serum immunity (IgA and IgG) against WCE, pertussis toxin (PT), FHA, PRN, and any additional anti-pertussis antibodies identified during assay development (FIM 2/3) using GMC |
| Serum IgG: Proportion of Subjects With Antibody Concentration ≥0.1 Immunogenicity Serum IgG for Diphtheria, Tetanus | Day 29 | Serum IgG levels against diphtheria, tetanus by treatment groups (BPZE1 + Boostrix vs Boostrix) |
| Safety: Reactogenicity and AEs | Through 7 days, 28 days, and 169 days (EOS) following any study vaccination respectively | To describe reactogenicity events during the 7 days following any study vaccination (7 days after Day 1 study vaccination and 7 days after Day 85 attenuated challenge with open-label BPZE1), all AEs through 28 days following Day 1 study vaccination and Day 85 attenuated challenge with open-label BPZE1, medically-attended AEs (MAAE) through 84 days following Day 1 study vaccination and Day 85 attenuated challenge with open-label BPZE1, AEs of special interest (AESIs) and serious adverse events (SAE) through Day 169 (EOS). |
| Colonization (Substudy Only) | Day 92 or Day 99. | Proportion of subjects with positive B. pertussis by culture or polymerase chain reaction \[PCR\]) following re-vaccination/attenuated challenge (BPZE1, BPZE1 + Boostrix, BPZE1 and BPZE1 + Boostrix, Boostrix control) |
| Serum Immunogenicity IgA and IgG GMFR | Baseline, Day 29 | Induction of serum immunity (IgA and IgG) against WCE, pertussis toxin (PT), FHA, PRN, and any additional anti-pertussis antibodies identified during assay development (FIM 2/3) using GMFR |
| Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Day 29 | Serum IgG levels against acellular pertussis antigens (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\], pertactin \[PRN\]) by treatment groups (BPZE1 + Boostrix vs Boostrix) |
Countries
Australia, Costa Rica, United Kingdom
Participant flow
Recruitment details
381 participants screened; 368 participants randomized (2 participants randomized but not vaccinated); 366 participants vaccinated. Participants were grouped by age: 6-10 years and 11-17 years with a Safety Lead-in group of 45 participants in the older age group. All participants were in the study from 11-Nov-2021 through 15-May-2024 Period 1 (Day 1): Vaccination; Period 2 (Day 85): Optional Attenuated Challenge Substudy
Participants by arm
| Arm | Count |
|---|---|
| BPZE1 and Intramuscular Placebo Participants received an intranasal dose of BPZE1 via the mucosal atomization device and a dose of intramuscular placebo. | 123 |
| BPZE1 and Boostrix Intramuscular Participants received an intranasal dose of BPZE1 via the mucosal atomization device and a dose of intramuscular Boostrix (acellular pertussis \[aP\] vaccine). | 121 |
| Placebo Intranasal and Boostrix Intramuscular Participants received an intranasal dose of placebo via the mucosal atomization device and a dose of intramuscular Boostrix (aP vaccine comparator). | 122 |
| Total | 366 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Study | Lost to Follow-up | 0 | 2 | 2 |
| Study | Withdrawal by Subject | 5 | 2 | 1 |
Baseline characteristics
| Characteristic | BPZE1 and Intramuscular Placebo | BPZE1 and Boostrix Intramuscular | Placebo Intranasal and Boostrix Intramuscular | Total |
|---|---|---|---|---|
| Age, Continuous | 10.9 years STANDARD_DEVIATION 2.7 | 10.8 years STANDARD_DEVIATION 2.9 | 10.7 years STANDARD_DEVIATION 2.8 | 10.8 years STANDARD_DEVIATION 2.8 |
| Age, Customized 11-17 years | 63 Participants | 54 Participants | 57 Participants | 174 Participants |
| Age, Customized 6-10 years | 60 Participants | 67 Participants | 65 Participants | 192 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 60 Participants | 58 Participants | 58 Participants | 176 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 63 Participants | 63 Participants | 64 Participants | 190 Participants |
| Race/Ethnicity, Customized Aboriginal or Torres Strait Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Asian | 3 Participants | 6 Participants | 0 Participants | 9 Participants |
| Race/Ethnicity, Customized Black | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Mixed or Multiple Ethnic Group | 6 Participants | 4 Participants | 10 Participants | 20 Participants |
| Race/Ethnicity, Customized Other Race | 60 Participants | 59 Participants | 57 Participants | 176 Participants |
| Race/Ethnicity, Customized Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized White | 54 Participants | 52 Participants | 55 Participants | 161 Participants |
| Region of Enrollment Australia | 27 participants | 23 participants | 27 participants | 77 participants |
| Region of Enrollment Costa Rica | 73 participants | 75 participants | 73 participants | 221 participants |
| Region of Enrollment United Kingdom | 23 participants | 23 participants | 22 participants | 68 participants |
| Sex: Female, Male Female | 60 Participants | 56 Participants | 54 Participants | 170 Participants |
| Sex: Female, Male Male | 63 Participants | 65 Participants | 68 Participants | 196 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 123 | 0 / 121 | 0 / 122 | 0 / 38 | 0 / 36 | 0 / 46 |
| other Total, other adverse events | 31 / 123 | 19 / 121 | 26 / 122 | 4 / 38 | 10 / 36 | 10 / 46 |
| serious Total, serious adverse events | 1 / 123 | 0 / 121 | 2 / 122 | 0 / 38 | 0 / 36 | 0 / 46 |
Outcome results
Primary
Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29
Geometric mean fold rise (GMFR) of mucosal S-IgA against whole cell extract (WCE) by treatment arm (BPZE1, BPZE1 + Boostrix) at Day 29.
Time frame: Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| BPZE1 and Intramuscular Placebo | Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29 | 3.8 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29 | 3.5 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Geometric Mean Fold Rise (GMFR) of Mucosal Immunogenicity S-IgA Against Whole Cell Extract at Day 29 | 1.2 Fold Rise |
Primary
Safety: Solicited Adverse Events (AEs)
Solicited AEs (local injection site, nasal/respiratory, and systemic reactogenicity events)
Time frame: Through 7 days following first study vaccination.
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Safety: Solicited Adverse Events (AEs) | Local injection site reactogenicity | 59 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Solicited Adverse Events (AEs) | Systemic reactogenicity | 51 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Solicited Adverse Events (AEs) | Nasal/Respiratory reactogenicity | 61 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Solicited Adverse Events (AEs) | Local injection site reactogenicity | 81 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Solicited Adverse Events (AEs) | Systemic reactogenicity | 60 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Solicited Adverse Events (AEs) | Nasal/Respiratory reactogenicity | 63 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Solicited Adverse Events (AEs) | Systemic reactogenicity | 67 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Solicited Adverse Events (AEs) | Nasal/Respiratory reactogenicity | 55 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Solicited Adverse Events (AEs) | Local injection site reactogenicity | 88 Participants |
Secondary
Colonization (Substudy Only)
Proportion of subjects with positive B. pertussis by culture or polymerase chain reaction \[PCR\]) following re-vaccination/attenuated challenge (BPZE1, BPZE1 + Boostrix, BPZE1 and BPZE1 + Boostrix, Boostrix control)
Time frame: Day 92 or Day 99.
Population: Investigational quantitative PCR not sensitive, no cultures performed and no results available.
Secondary
Mucosal Immunogenicity S-IgA GMFR
Induction of normalized S-IgA against WCE, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development (FIM 2/3) using GMFR
Time frame: Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMFR | Day 29 FHA | 8.1 Fold Rise |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMFR | Day 29 PRN | 3.7 Fold Rise |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMFR | Day 29 WCE | 3.8 Fold Rise |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMFR | Day 29 PT | 1.7 Fold Rise |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMFR | Day 29 FIM 2/3 | 14.0 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 PRN | 4.2 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 WCE | 3.5 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 PT | 1.7 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 FHA | 6.8 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 FIM 2/3 | 10.5 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 FIM 2/3 | 1.3 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 FHA | 2.1 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 WCE | 1.2 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 PRN | 1.5 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMFR | Day 29 PT | 1.2 Fold Rise |
Secondary
Mucosal Immunogenicity S-IgA GMR
Induction of normalized S-IgA against WCE, PT, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development (fimbriae serotype 2 and 3; FIM 2/3) using GMR
Time frame: Baseline, Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Day 29 FHA | 18.6 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Baseline FHA | 2.3 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Day 29 PRN | 11.4 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Baseline WCE | 27.2 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Baseline FIM 2/3 | 3.0 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Day 29 FIM 2/3 | 42.4 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Baseline PT | 4.0 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Day 29 WCE | 104.0 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Baseline PRN | 3.0 AU/(mg S-IgA) |
| BPZE1 and Intramuscular Placebo | Mucosal Immunogenicity S-IgA GMR | Day 29 PT | 6.8 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 FHA | 15.7 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 PT | 6.5 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline PT | 3.8 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 PRN | 13.6 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 FIM 2/3 | 26.9 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline PRN | 3.3 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline FHA | 2.3 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline FIM 2/3 | 2.6 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline WCE | 24.8 AU/(mg S-IgA) |
| BPZE1 and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 WCE | 86.3 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 FIM 2/3 | 3.0 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline WCE | 22.4 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline PT | 3.5 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline FHA | 2.2 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline FIM 2/3 | 2.3 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 WCE | 27.4 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 PT | 4.3 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 PRN | 4.0 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Day 29 FHA | 4.7 AU/(mg S-IgA) |
| Placebo Intranasal and Boostrix Intramuscular | Mucosal Immunogenicity S-IgA GMR | Baseline PRN | 2.7 AU/(mg S-IgA) |
Secondary
Safety: Reactogenicity and AEs
To describe reactogenicity events during the 7 days following any study vaccination (7 days after Day 1 study vaccination and 7 days after Day 85 attenuated challenge with open-label BPZE1), all AEs through 28 days following Day 1 study vaccination and Day 85 attenuated challenge with open-label BPZE1, medically-attended AEs (MAAE) through 84 days following Day 1 study vaccination and Day 85 attenuated challenge with open-label BPZE1, AEs of special interest (AESIs) and serious adverse events (SAE) through Day 169 (EOS).
Time frame: Through 7 days, 28 days, and 169 days (EOS) following any study vaccination respectively
Population: Safety Analysis Set for Day 1 includes all vaccinated participants. Safety Analysis Set for Day 85 includes all Attenuated Challenge Open-label BPZE1 Substudy participants.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | MAAEs | 25 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Reactogenicity after Day 85 attenuated challenge with open-label BPZE1 : Nasal/Respiratory | 19 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | AESI | 4 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Day 85 AEs | 4 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Reactogenicity after Day 85 attenuated challenge with open-label BPZE1 : Systemic | 19 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Nasal/Respiratory | 61 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Local injection site | 59 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | SAEs | 1 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Systemic | 51 Participants |
| BPZE1 and Intramuscular Placebo | Safety: Reactogenicity and AEs | Day 29 AEs | 31 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | AESI | 6 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Local injection site | 81 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Nasal/Respiratory | 63 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Systemic | 60 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 85 attenuated challenge with open-label BPZE1 : Nasal/Respiratory | 16 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 85 attenuated challenge with open-label BPZE1 : Systemic | 14 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Day 29 AEs | 19 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Day 85 AEs | 10 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | MAAEs | 12 Participants |
| BPZE1 and Boostrix Intramuscular | Safety: Reactogenicity and AEs | SAEs | 0 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | SAEs | 2 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Day 85 AEs | 10 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Systemic | 67 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Local injection site | 88 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | MAAEs | 23 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 1 study vaccination : Nasal/Respiratory | 55 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 85 attenuated challenge with open-label BPZE1 : Systemic | 22 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | AESI | 3 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Day 29 AEs | 26 Participants |
| Placebo Intranasal and Boostrix Intramuscular | Safety: Reactogenicity and AEs | Reactogenicity after Day 85 attenuated challenge with open-label BPZE1 : Nasal/Respiratory | 24 Participants |
Secondary
Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens
Serum IgG levels against acellular pertussis antigens (pertussis toxin \[PT\], filamentous hemagglutinin \[FHA\], pertactin \[PRN\]) by treatment groups (BPZE1 + Boostrix vs Boostrix)
Time frame: Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Serum IgG against PRN | 116.2 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Serum IgG against FHA | 502.9 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Serum IgG against PT | 88.1 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Serum IgG against PRN | 82.5 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Serum IgG against FHA | 458.2 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum IgG: Geometric Mean Concentration (GMC) Against Acellular Pertussis Antigens | Serum IgG against PT | 84.4 IU/ml |
Secondary
Serum IgG: Proportion of Subjects With Antibody Concentration ≥0.1 Immunogenicity Serum IgG for Diphtheria, Tetanus
Serum IgG levels against diphtheria, tetanus by treatment groups (BPZE1 + Boostrix vs Boostrix)
Time frame: Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Serum IgG: Proportion of Subjects With Antibody Concentration ≥0.1 Immunogenicity Serum IgG for Diphtheria, Tetanus | Serum IgG against Diphtheria >= 0.1 IU/ml | 111 Participants |
| BPZE1 and Intramuscular Placebo | Serum IgG: Proportion of Subjects With Antibody Concentration ≥0.1 Immunogenicity Serum IgG for Diphtheria, Tetanus | Serum IgG against Tetanus >= 0.1 IU/ml | 111 Participants |
| BPZE1 and Boostrix Intramuscular | Serum IgG: Proportion of Subjects With Antibody Concentration ≥0.1 Immunogenicity Serum IgG for Diphtheria, Tetanus | Serum IgG against Diphtheria >= 0.1 IU/ml | 109 Participants |
| BPZE1 and Boostrix Intramuscular | Serum IgG: Proportion of Subjects With Antibody Concentration ≥0.1 Immunogenicity Serum IgG for Diphtheria, Tetanus | Serum IgG against Tetanus >= 0.1 IU/ml | 109 Participants |
Secondary
Serum Immunogenicity IgA and IgG GMC
Induction of serum immunity (IgA and IgG) against WCE, pertussis toxin (PT), FHA, PRN, and any additional anti-pertussis antibodies identified during assay development (FIM 2/3) using GMC
Time frame: Baseline, Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 PT | 31.3 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 PRN | 29.3 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 PRN | 10.8 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Baseline PRN | 1.5 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 FHA | 130.8 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Baseline PRN | 7.6 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Baseline PT | 1.5 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 FIM 2/3 | 107.1 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 FIM 2/3 | 45.2 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Baseline WCE | 12.3 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 PT | 4.3 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Baseline FHA | 31.3 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 FHA | 20.0 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 WCE | 53.0 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Baseline FIM 2/3 | 14.3 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Baseline PT | 7.8 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Baseline FIM 2/3 | 2.9 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 WCE | 111.4 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgG Baseline WCE | 42.4 IU/ml |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMC | IgA Baseline FHA | 2.2 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 PRN | 25.0 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline WCE | 52.5 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline PT | 8.5 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline PRN | 8.5 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline FHA | 42.9 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline FIM 2/3 | 12.9 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 WCE | 229.2 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 PRN | 116.2 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 FHA | 502.9 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 FIM 2/3 | 80.2 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline WCE | 14.7 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline PT | 1.6 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline PRN | 1.9 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline FHA | 2.8 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline FIM 2/3 | 2.9 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 WCE | 56.6 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 PT | 4.4 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 PT | 88.1 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 FHA | 33.6 IU/ml |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 FIM 2/3 | 31.1 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 PRN | 6.9 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline FHA | 3.3 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline FIM 2/3 | 13.3 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline WCE | 51.5 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline FIM 2/3 | 3.3 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline FHA | 46.2 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 FIM 2/3 | 4.5 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 WCE | 25.7 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline PRN | 8.4 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 FHA | 21.1 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 FIM 2/3 | 21.5 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Day 29 PT | 2.6 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline WCE | 14.7 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 FHA | 458.2 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Baseline PT | 9.1 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline PT | 1.7 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 PRN | 82.5 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 PT | 84.4 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgA Baseline PRN | 1.7 IU/ml |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMC | IgG Day 29 WCE | 164.9 IU/ml |
Secondary
Serum Immunogenicity IgA and IgG GMFR
Induction of serum immunity (IgA and IgG) against WCE, pertussis toxin (PT), FHA, PRN, and any additional anti-pertussis antibodies identified during assay development (FIM 2/3) using GMFR
Time frame: Baseline, Day 29
Population: Per protocol immunogenicity analysis set
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 PT | 2.9 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 PRN | 3.8 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 PRN | 6.7 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 FHA | 9.0 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 WCE | 2.6 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 FIM 2/3 | 15.4 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 FHA | 4.2 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 PT | 4.0 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 FIM 2/3 | 7.4 Fold Rise |
| BPZE1 and Intramuscular Placebo | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 WCE | 4.2 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 PT | 2.7 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 FHA | 11.9 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 WCE | 3.9 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 PRN | 13.9 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 PRN | 14.5 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 WCE | 4.4 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 FIM 2/3 | 6.4 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 PT | 10.4 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 FIM 2/3 | 10.9 Fold Rise |
| BPZE1 and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 FHA | 12.3 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 FIM 2/3 | 1.4 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 WCE | 3.3 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 PT | 9.3 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 PRN | 9.6 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 FHA | 9.9 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgG Day 29 FIM 2/3 | 1.7 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 WCE | 1.7 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 PT | 1.6 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 PRN | 4.1 Fold Rise |
| Placebo Intranasal and Boostrix Intramuscular | Serum Immunogenicity IgA and IgG GMFR | IgA Day 29 FHA | 6.7 Fold Rise |