First Adult Safety Trial on Nasal Live Attenuated B. Pertussis Vaccine

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety and immunogenicity of a new live attenuated vaccine against whooping-cough. It is a phase1, single centre, dose-escalating, placebo-controlled study on a genetically modified B. pertussis strain given as a single intranasal dose to healthy adult male volunteers. Effective vaccines are needed to protect young infants (from 0 to 6 months, today the most vulnerable age group), preferably after a single administration very early in life. The successful outcome of this project would constitute an important milestone towards nasal vaccination of infants, possibly at birth with a novel, single-dose pertussis vaccine. Our ultimate aim is to protect infants in the most vulnerable age group, before the regular vaccination schedule using already available vaccines is applied. The ultimate aim is thus not to replace current vaccination schedules with available vaccines, but to add a first nasal vaccination to protect very early in life.

Official Title
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A Phase 1, Single Centre, Dose-escalating, Placebo-controlled Study of a Genetically Modified B. Pertussis Strain Given as a Single Intranasal Dose to Healthy Adult Male Volunteers

Conditions
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Pertussis

Intervention / Treatment
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* Biological: BPZE1
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject will be included in the study if he meets all the following criteria: Healthy male born between 1979 and 1991 who has not experienced clinical pertussis (lab. Verified) during the past 10 years and who has not been vaccinated with any pertussis vaccine. Informed consent form signed by the subject. Subject shall be able to attend all scheduled visits and to understand and comply with the study procedures (e.g. able to read and write Swedish). Exclusion Criteria: If any of the following criteria are met, the subject must not be included in the study: Individuals with pertussis toxin serum IgG antibodies ≥20 units/mL. Blood pressure after resting ≥ 150/90 mmHg. Heart rate after resting ≥80 bpm. Respiratory rate after resting ≥ 20/minute. Unwillingness to refrain from the use of nicotine products from screening through day 28. Use of narcotic drugs/alcohol and/or a history of previous use of drug/alcohol abuse whitin 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. Use of corticosteroids in the respiratory tract(e.g. nasal steroids, inhaled steroids) whitin 30 days prior to day 0. Use of herbal medications or dietary supplements within 7 days prior to day 0 at the discretion of the investigator. Unwillingness to refrain from herbal medications or dietary supplements within 30 days after day 0 at the discretion of the investigator. Receipt of a vaccine within the last 30 days prior to day 0 or planned vaccination within the next 30 days after day 0. Evolving encephalopathy not attributable to another identifiable cause within 7 days of administration of a previous dose of any vaccine. 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 history of congenital or hereditary immunodeficiency (first degree). Infection with HIV, hepatitis B or C. Any medical condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives. Clinically significant abnormal laboratory values at the discretion of the investigator. Person in frequent contact with children less than 1 year of age (father, childcare worker, nurse, etc…) or residence in the same household as persons with known immunodeficiency.

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 31 Years

Sexes Eligible for Study
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Male

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 - Low dose<br>1,000 colony forming units (cfu) of BPZE1 | Biological: BPZE1<br>* Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).<br>|
| Experimental: BPZE1- middle dose<br>100,000 colony forming units (cfu) of BPZE1 | Biological: BPZE1<br>* Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).<br>|
| Experimental: BPZE1 - High dose<br>10,000,000 colony forming units (cfu) of BPZE1 | Biological: BPZE1<br>* Individuals will be vaccinated once intranasally with the designated dose of BPZE1 Dose 2 x 0.1 mL (0.1 mL per nostril).<br>|
| Placebo Comparator: Placebo<br>Formulation buffer | Biological: Placebo<br>* Individuals will get placebo once intranasally. Dose 2 x 0.1 mL (0.1 mL per nostril).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| General safety and local tolerability in the respiratory tract of a single ascending dose of the genetically modified B. pertussis strain | To determine general safety, i. e. general well-being of the volunteers and any symptoms felt by the volunteers with onset within one month after vaccine administration. vital signs: Blood pressure, heart rate, respiratory rate, oral temperature. abnormalities in the following laboratory data: Haemoglobin, total and differential white blood cell count, platelets (thrombocytes). specific side effects: Local symptoms from the respiratory tract: Sneezing, swollen nose, cough, bleeding from the nose, pain or other symptoms from the ear, symptoms from the eyes (redness, secretion). | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Attachment of the BPZE1 strain to the nasopharyngeal mucosa | Detection of colonizing BPZE1 bacteria in nasopharyngeal culture | Up to 50 days after vaccination | 
| Immunogenicity | Immune responses will be determined by serum IgG and IgA, IgG and IgA in saliva and nasopharyngeal aspirate, cytokines and numbers of effector and memory T and B cells after stimulation with the various B. pertussis antigens. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Live nasal vaccine for prevention of pertussis