Periscope Phase C Bordetella Pertussis Human Challenge Study With Delayed Antibiotic Therapy for 6 Weeks

• Status: Recruiting
• Trial end date: 2024-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Primary objective- To assess the safety of nasal inoculation of healthy volunteers with B. pertussis with antibiotic therapy given to eradicate colonisation at 6 weeks after inoculation or at symptom onset, whichever occurs first

Secondary objectives - To measure the rate of natural clearance of carriage of B. pertussis following nasal inoculation

• To assess the kinetics of B. pertussis colonisation density following nasal inoculation

• To describe the microevolution of B. pertussis and adaptation of the resident microbiome during B. pertussis carriage

• To measure B. pertussis-specific antibody and cellular immunological responses in healthy volunteers during colonisation with B. pertussis - To identify biomarkers that correlate with natural clearance of B. pertussis carriage after induced B. pertussis colonisation

• To detect transmission of B. pertussis to bedroom contacts of inoculated volunteers during prolonged asymptomatic colonisation

• Phase: N/A
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Southampton
• Treatments: Azithromycin

Criteria

Inclusion Criteria:

• Healthy adults aged 18 to 55 years inclusive on the day of screening

• Fully conversant in the English language

• Able to communicate easily by both mobile telephone, email and text messaging

• Able and willing (in the investigator's opinion) to comply with all study requirements

• Written informed consent to participate in the study

• Willingness to take a curative antibiotic regimen if / when required according to the study protocol

• Willingness to abide by infection control guidelines during social contact for the duration of their participation in the study

• Willingness to attend to the National Institute for Health Research (NIHR) Clinical Research Facility (CRF) Southampton immediately if they become symptomatic

• Agreement to have no bedroom contacts other than their corresponding contact/challenge volunteer between inoculation and 6 weeks after inoculation

• Able to answer all questions on the pre-consent questionnaire correctly

Exclusion Criteria:

• Individuals living in the same households as:

1. unimmunised or partially immunised children and infants aged < 1 year

2. pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact

3. immunosuppressed individuals

4. frail individuals

5. healthcare workers regularly working with vulnerable individuals as above

• Individuals who have inviolable commitments within the study period (from day 0 to week 6 + 2 days) to be in close contact with:

1. unimmunised or partially immunised children and infants aged < 1 year

2. pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact

3. immunosuppressed individuals

4. frail individuals

• Individuals who live in a boarding school or dormitory during the study.

• B. pertussis detected on nasal wash taken before the initial challenge

• Individuals with a confirmed or suspected infection at the time of inoculation with B. pertussis

• Individuals who have participated in other interventional clinical trials in the last 12 weeks

• Individuals who have a history of receiving B. pertussis vaccination in the last 5 years

• Individuals who have previously participated in a B. pertussis human challenge study

• Individuals who have had a proven B. pertussis infection in the last 5 years

• Individuals who have a history of never being vaccinated against B. pertussis

• Current smokers defined as having had a cigarette/cigar in the last week (including vaping)

• Use of systemic antibiotics within 30 days of or during the challenge

• Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)

• Use of immunoglobulins or blood products within 3 months prior to enrolment

• History of allergic disease or reactions likely to be exacerbated by any component of the inoculum

• Contraindications to the use of azithromycin or macrolides

• Pregnancy, lactation or intention to become pregnant during the study

• Any clinically significant abnormal finding on biochemistry, haematology, toxicology or serological blood tests, urinalysis (see The following reference ranges are provided for the purpose of guidance only. Results that fall outside of these ranges may not be of clinical significance but should be considered on an individual basis.) or clinical examination - in the event of abnormal test results, confirmatory repeat tests will be requested

• Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data, for example recent surgery to the nasopharynx

Exclusion criteria - Contact volunteers

• Individuals living in the same households as:

1. unimmunised or partially immunised children and infants aged < 1 year

2. pregnant women

3. immunosuppressed individuals

4. frail individuals

5. healthcare workers working with vulnerable individuals as above

• Individuals who have inviolable commitments within the study period (from day 0 to week 6 + 2 days) to be in close contact with:

1. unimmunised or partially immunised children and infants aged < 1 year

2. pregnant women >32 weeks who have not received pertussis vaccination at least a week prior to contact

3. immunosuppressed individuals

4. frail individuals

• Individuals who have been involved in other clinical trials involving receipt of an investigational product over the last 12 weeks or if there is planned use of an investigational product during the study period

• Individuals who have previously participated in a B. pertussis human challenge study

• Individuals who have a history of never being vaccinated against B. pertussis

• Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; malignancy, asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)

• Contraindications to the use of azithromycin or macrolides

• Any clinically significant abnormal finding on clinical examination

• Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data

• Pregnancy, lactation or intention to become pregnant during the study