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.
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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
QUADRUPLE
Enrollment
368
Live attenuated pertussis vaccine and placebo
Live attenuated pertussis vaccine and tetanus, diphtheria, and aP vaccine
Tetanus, diphtheria, and aP vaccine and placebo
Sydney Children's Hospital
Randwick, New South Wales, Australia
Sydney Children's Hospital
Westmead, New South Wales, Australia
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
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.
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
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
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
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
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Women's and Children's Hospital
North Adelaide, South Australia, Australia
University of Melbourne
Melbourne, Victoria, Australia
Telethon Kids Institute
Nedlands, Western Australia, Australia
CSA Clinica San Augustin
San José, Costa Rica
IICIMED Instituto de Investigacion en Ciencias Medicas
San José, Costa Rica
MRI, Metropolitan Research Institute
San José, Costa Rica
Birmingham Children's Hospital NHS Foundation Trust
Birmingham, United Kingdom
Bradford Royal Infirmary
Bradford, United Kingdom
...and 6 more locations
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
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
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
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.