Immunogenicity and Safety of BPZE1 Intranasal Pertussis Vaccine in Healthy School-age Children

Study Overview
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Brief Summary
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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
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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.

Official Title
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Phase 2b Placebo-Controlled Randomized Study of BPZE1 Intranasal Pertussis Vaccine in Healthy School-Age Children to Assess Immunological Response and Safety of a Single Dose BPZE1 With/Without Coadministration of Tdap (Boostrix™)

Conditions
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Bordetella Pertussis, Whooping Cough

Intervention / Treatment
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* Biological: BPZE1 pertussis vaccine and placebo
* Biological: BPZE1 pertussis vaccine and Boostrix
* Biological: Placebo and Boostrix


Participation Criteria
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Eligibility Criteria
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Key Inclusion Criteria: Male or female subject 6 to 17 years of age on Day 1. Subject must provide informed consent (assent, depending on age) prior to participation in study and comply with protocol requirements. 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. Subject has a stable health status, as established by physical examination, vital sign measurements, and medical history. 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. 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: History of pertussis-containing vaccination or documented pertussis infection within 3 years prior to Day 1 and/or a history of Td-containing vaccination (without pertussis component) within 1 month prior to Day 1. Chronic significant illness actively being treated or a history of recent intervention for worsening or fluctuating symptoms (at the discretion of the investigator). History of cancer (malignancy). Congenital, hereditary, or acquired disease or disorder classified as autoimmune, immunodeficient, coagulopathy, hepatic, renal, neurologic, or cognitive. 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. 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. 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. History of oro/nasopharynx surgery (eg, adenoidectomy, tonsillectomy) within 60 days prior to Day 1. 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. Subject has routine and/or repeated contact with, or is currently living in a household with, an immunocompromised individual. Subject resides in a residence where an infant less than 6 months of age resides or may reside.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BPZE1 intranasal and Placebo intramuscular<br>Individual will receive an intranasal dose of BPZE1 via the mucosal atomization device and a dose of intramuscular placebo. | Biological: BPZE1 pertussis vaccine and placebo<br>* Live attenuated pertussis vaccine and placebo<br>|
| Experimental: BPZE1 intranasal and Boostrix intramuscular<br>Individual will receive an intranasal dose of BPZE1 via the mucosal atomization device and a dose of intramuscular Boostrix (acellular pertussis [aP] vaccine). | Biological: BPZE1 pertussis vaccine and Boostrix<br>* Live attenuated pertussis vaccine and tetanus, diphtheria, and aP vaccine<br>|
| Active Comparator: Placebo intranasal and Boostrix intramuscular<br>Individual will receive an intranasal dose of placebo via the mucosal atomization device and a dose of intramuscular Boostrix (aP vaccine comparator). | Biological: Placebo and Boostrix<br>* Tetanus, diphtheria, and aP vaccine and placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titer (GMT) of Mucosal Immunogenicity S-IgA | Geometric mean titer (GMT) of mucosal S-IgA against whole cell extract (WCE) by treatment arm (BPZE1, BPZE1 + Boostrix, Boostrix control). | Day 29 | 
| Geometric mean fold rise (GMFR) of Mucosal Immunogenicity S-IgA | Geometric mean fold rise (GMFR) of mucosal S-IgA against whole cell extract (WCE) by treatment arm (BPZE1, BPZE1 + Boostrix, Boostrix control). | Day 29 | 
| Immunogenicity Serum IgG: proportion of subjects with antibody concentration ≥0.1 Immunogenicity Serum IgG for diphtheria, tetanus and acellular pertussis antigens | Serum IgG levels against diphtheria, tetanus and acellular pertussis antigens (pertussis toxin [PT], filamentous hemagglutinin [FHA], pertactin [PRN]) by treatment groups (BPZE1 + Boostrix vs Boostrix) | Day 29 | 
| 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) | Day 92 or Day 99. | 
| Safety: Solicited Adverse Events (AEs) | Solicited AEs (local, nasal/respiratory, and systemic reactogenicity events) | Through 7 days following first study vaccination. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mucosal Immunogenicity S-IgA | Induction of S-IgA against WCE, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development using GMT | Day 29, Day 85, Day 169 (EOS). | 
| Mucosal Immunogenicity S-IgA | Induction of S-IgA against WCE, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development using GMFR | Day 29, Day 85, Day 169 (EOS). | 
| Serum Immunogenicity S-IgA and IgG | Induction of serum immunity (IgA and IgG) against WCE, pertussis toxin (PT), FHA, PRN, and any additional anti-pertussis antibodies identified during assay development using GMT | Baseline, Day 29, Day 85, Day 169 (EOS). | 
| Serum Immunogenicity S-IgA and IgG | Induction of serum immunity (IgA and IgG) against WCE, pertussis toxin (PT), FHA, PRN, and any additional anti-pertussis antibodies identified during assay development using GMFR | Baseline, Day 29, Day 85, Day 169 (EOS). | 
| Safety: Reactogenicity and AEs | To describe reactogenicity events during the 7 days following any study vaccination, all AEs through 28 days following study vaccination, medically-attended AEs through 84 days following study vaccination, AEs of special interest (AESIs) and serious adverse events (SAE) through Day 169 (EOS), and incidence of severe acute respiratory syndrome-corona virus-2 (SARS-CoV-2) infections or AESIs. | Through 7 days, 28 days, and 169 days (EOS) following any study vaccination. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bordetella pertussis (B. pertussis), Whooping Cough, BPZE1, Boostrix, Vaccine, Children, Booster, Live attenuated vaccine