MedPath

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

Phase 2
Completed
Conditions
Bordetella Pertussis, Whooping Cough
Interventions
Biological: BPZE1 pertussis vaccine and Boostrix
Biological: BPZE1 pertussis vaccine and placebo
Biological: Placebo and Boostrix
Registration Number
NCT05116241
Lead Sponsor
ILiAD Biotechnologies
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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
367
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. 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.
  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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
BPZE1 intranasal and Boostrix intramuscularBPZE1 pertussis vaccine and BoostrixIndividual will receive an intranasal dose of BPZE1 via the mucosal atomization device and a dose of intramuscular Boostrix (acellular pertussis \[aP\] vaccine).
BPZE1 intranasal and Placebo intramuscularBPZE1 pertussis vaccine and placeboIndividual will receive an intranasal dose of BPZE1 via the mucosal atomization device and a dose of intramuscular placebo.
Placebo intranasal and Boostrix intramuscularPlacebo and BoostrixIndividual will receive an intranasal dose of placebo via the mucosal atomization device and a dose of intramuscular Boostrix (aP vaccine comparator).
Primary Outcome Measures
NameTimeMethod
Immunogenicity Serum IgG: proportion of subjects with antibody concentration ≥0.1 Immunogenicity Serum IgG for diphtheria, tetanus and acellular pertussis antigensDay 29

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)

Geometric mean titer (GMT) of Mucosal Immunogenicity S-IgADay 29

Geometric mean titer (GMT) of mucosal S-IgA against whole cell extract (WCE) by treatment arm (BPZE1, BPZE1 + Boostrix, Boostrix control).

Geometric mean fold rise (GMFR) of Mucosal Immunogenicity S-IgADay 29

Geometric mean fold rise (GMFR) of mucosal S-IgA against whole cell extract (WCE) by treatment arm (BPZE1, BPZE1 + Boostrix, Boostrix control).

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)

Safety: Solicited Adverse Events (AEs)Through 7 days following first study vaccination.

Solicited AEs (local, nasal/respiratory, and systemic reactogenicity events)

Secondary Outcome Measures
NameTimeMethod
Mucosal Immunogenicity S-IgADay 29, Day 85, Day 169 (EOS).

Induction of S-IgA against WCE, FHA, PRN, and any additional anti-pertussis mucosal antibodies identified during assay development using GMFR

Serum Immunogenicity S-IgA and IgGBaseline, Day 29, Day 85, Day 169 (EOS).

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

Safety: Reactogenicity and AEsThrough 7 days, 28 days, and 169 days (EOS) following any study vaccination.

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.

Trial Locations

Locations (15)

Telethon Kids Institute

🇦🇺

Nedlands, Western Australia, Australia

MRI, Metropolitan Research Institute

🇨🇷

San José, Costa Rica

Birmingham Children's Hospital NHS Foundation Trust

🇬🇧

Birmingham, United Kingdom

Sydney Children's Hospital

🇦🇺

Westmead, New South Wales, Australia

Women's and Children's Hospital

🇦🇺

North Adelaide, South Australia, Australia

Bradford Royal Infirmary

🇬🇧

Bradford, United Kingdom

Bristol Royal Hospital For Children

🇬🇧

Bristol, United Kingdom

Addenbrooke's Hospital

🇬🇧

Cambridge, United Kingdom

University of Melbourne

🇦🇺

Melbourne, Victoria, Australia

IICIMED Instituto de Investigacion en Ciencias Medicas

🇨🇷

San José, Costa Rica

CSA Clinica San Augustin

🇨🇷

San José, Costa Rica

Oxford Vaccine Group

🇬🇧

Oxford, United Kingdom

Leicester Children's Hospital, Ward 14, Level 4,

🇬🇧

Leicester, United Kingdom

University Hospital Southampton NHS Foundation Trust

🇬🇧

Southampton, United Kingdom

St George's Healthcare NHS Trust

🇬🇧

London, United Kingdom

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