Study of BPZE1 (High Dose) Nasal Live Attenuated B. Pertussis Vaccine

Study Overview
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Brief Summary
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This study evaluates the safety and immunogenicity of a higher dose formulation of a new live attenuated vaccine, BPZE1, intended to prevent Bordetella pertussis nasopharyngeal colonization and pertussis disease, and investigates whether higher doses of BPZE1 induce the live vaccine to colonize subjects' nasopharynx. The study is a Phase Ib (high dose), single centre, dose-escalating, placebo-controlled study of the live attenuated B. pertussis strain BPZE1 given as a single intranasal dose to healthy adult volunteer.

Official Title
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Phase Ib (High Dose), Single Centre, Dose-escalating, Placebo-controlled, Randomized Study of a Live Attenuated B. Pertussis Strain Given as a Single Intranasal Dose to Healthy Adult Volunteers

Conditions
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Pertussis, Whooping Cough

Intervention / Treatment
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* Biological: BPZE1
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy individual between 18 and 32 years of age, vaccinated or unvaccinated with acellular pertussis vaccine. Female subject of child bearing potential must be willing to ensure that they use a highly efficient method of contraception during the study (e.g. contraceptive pill, intrauterine contraceptive device). Informed consent form (ICF) signed by the subject. Subject shall be able to attend all scheduled visits and to understand and comply with the study procedures. Exclusion Criteria: Individual with PT and/or PRN serum IgG antibodies ≥20 International units/ml (IU/ml). NOTE! One control group with PRN serum IgG antibodies ≥ 20 IU/ml will be included. Vaccinated with the study vaccine in the Child Innovac study (EudraCT number 2010-019936-11). Pregnant or lactating women. Pregnancy not planned and to be avoided during the study by use of effective contraceptive methods. Blood pressure after resting ≥ 150/90 mm Hg at screening. Heart rate after resting ≥ 80 bpm at screening. Respiratory rate after resting ≥ 20/minute at screening. Unwillingness to refrain from the use of nicotine products from screening through day 28. Use of narcotic drugs and/or a history of drug/alcohol abuse with in the past 2 years prior to screening The subject has donated blood or suffered from blood loss of at least 450 ml (1 unit of blood) within 60 days prior to screening or donated plasma within 14 days prior to screening. Receipt of immunoglobulin, blood derived products, systemic corticosteroids or other immunosuppressant drugs within 90 days prior to day 0. Asthma or other chronic respiratory problems. Use of corticosteroids in the respiratory tract (e.g. nasal steroids, inhaled steroids) with in 30 days prior to day 0. Receipt of a vaccine within the last 30 days prior to day 0 or planned vaccination with in the next 30 days after day 0. Known hypersensitivity to any component of the study vaccine. Current participation in any other clinical trial or participation (and during the whole study) in any clinical trial in the previous 3 months prior to day 0. Inability to adhere to the protocol, including plans to move from the area. Family (first degree) history of congenital or hereditary immunodeficiency. Past or present infection with HIV, hepatitis B or C. Chronic conditions requiring ongoing active medical interventions, such as diabetes mellitus or cardiovascular disease. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic). Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or might affect the safety of the individual, e.g. evolving encephalopathy not attributable to another identifiable cause within 7 days of administration of a previous dose of any vaccine, hospitalization due to major depression or history of suicidal attempt. Abnormal laboratory values outside the limit of normal values for the screening laboratory with clinical significance at the discretion of the investigator. Person in 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 32 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 - 10,000,000 cfu<br>Individuals will be vaccinated once intranasally with the designated dose of BPZE1 or Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril). | Biological: BPZE1<br>* Intranasal live, attenuated vaccine<br>Other: Placebo<br>* Diluent<br>|
| Experimental: BPZE1 - 100,000,000 cfu<br>Individuals will be vaccinated once intranasally with the designated dose of BPZE1 or Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril). | Biological: BPZE1<br>* Intranasal live, attenuated vaccine<br>Other: Placebo<br>* Diluent<br>|
| Experimental: BPZE1 - 1,000,000,000 cfu<br>Individuals will be vaccinated once intranasally with the designated dose of BPZE1 or Placebo at a Dose 2 x 0.4 mL (0.4 mL per nostril). | Biological: BPZE1<br>* Intranasal live, attenuated vaccine<br>Other: Placebo<br>* Diluent<br>|
| Experimental: BPZE1 - High Antibody 1,000,000,000 cfu<br>Individuals will be vaccinated once intranasally with the designated dose of BPZE1 at a Dose 2 x 0.4 mL (0.4 mL per nostril). | Biological: BPZE1<br>* Intranasal live, attenuated vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Primary Safety Endpoint is the Number and Percentage of Participants Per Dose Group and Randomized Allocation, With at Least One of the Following Adverse Events Between Day 0 and Day 28 | Percentage is based on subjects experiencing at least one of the following events: Cough and spasmodic cough of grade 2 or higher Other respiratory tract AE related or possibly related to vaccination of grade 3 or higher Any other AE related or possibly related to vaccination of grade 3 or higher | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of Subjects With BPZE1 Colonization | To assess the proportion of subjects having positive colonization of the human respiratory tract by live attenuated B. pertussis strain BPZE1 per group at any time period measured at 4, 7, 11, 14, 21 and 28 days post vaccination. | 28 days | 
| The Proportion of Subjects That Have an Antibody Response to BPZE1 Vaccination | To assess the number of immune responders and levels of Immunoglobulin G/Immunoglobulin A (IgG/IgA) antibodies to pertussis toxin (PT), filamentous haemagglutinin adhesin (FHA), Pertactin (PRN), and fimbriae 2/3 in serum and nasopharyngeal aspirate. A positive antibody response after vaccination is defined as at least 100% increase from pre- to post-vaccination, to at least 4 times minimum level of detection (MLD) for PT, FHA, PRN, and fimbriae 2/3 in the post-vaccination sample. The 4 antigens described are the standard 4 antigens historically used to describe a serum immunological response to B. pertussis. The absolute serum antibody titers have not shown a correlation of protection in previous pertussis vaccine studies of the current acellular vaccine and there is no known serum antigen threshold of protection for pertussis. Antibodies are measured before vaccination and at 4, 7, 11, 14, 21, 28 days, 6-months and 12-months post-vaccination. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pertussis, Colonization, Vaccine, Immune response, BPZE1, Infection, Bordetella pertussis, B. pertussis, respiratory Tract Infection