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

NCT05847322 | Recruiting DMC

• 2 other identifiers: IRAS 30421168737
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 1

Brief 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

Conditions

Pertussis/Whooping Cough

Outcome Measures

Primary Outcomes (4)

• To assess the incidence of solicited adverse events during prolonged colonisation with Bordetella pertussis following nasal inoculation of healthy adult volunteers

  • Participants will be asked about the occurrence of solicited adverse events at standardised visits. Any symptoms will be recorded and assessed by a study doctor. If deemed necessary by the study doctor further tests will be requested

  6 weeks.

• To assess the incidence of unsolicited adverse events during prolonged colonisation with Bordetella pertussis following nasal inoculation of healthy adult volunteers

  Participants will be asked about the occurrence of unsolicited adverse events at standardised visits. Any symptoms will be recorded and assessed by a study doctor. If deemed necessary by the study doctor further tests will be requested

  6 weeks.

• To establish the rate of natural clearance of Bordetella pertussis colonisation as detected by nasal wash.

  Bordetella pertussis colonisation will be measured weekly by culture of nasal washes. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).

  6 weeks.

• To establish the rate of natural clearance of Bordetella pertussis colonisation as detected by nasopharyngeal swab

  Bordetella pertussis colonisation will be measured weekly by culture of nasopharyngeal swabs. Putative positive cultures will be confirmed by polymerase chain reaction (PCR).

  6 weeks.

Secondary Outcomes (15)

• To establish the change in colonisation density of Bordetella pertussis during prolonged colonisation as measured from nasal wash samples

  6 weeks.

• To establish the change in colonisation density of Bordetella pertussis during prolonged colonisation as measured by nasopharyngeal swab samples

  6 weeks.

• To establish the occurrence of transmission to close contacts during prolonged Bordetella pertussis colonisation

  6 weeks.

• To establish any association between baseline anti-PT IgG level and protection from colonisation with Bordetella pertussis

  Day 0

• To establish any association between baseline anti-PRN IgG level and protection from colonisation with Bordetella pertussis

  Day 0

Study Arms (2)

Contact

OTHER

Contact volunteers are those volunteers whose partner/spouse is a Challenge volunteer. Investigators will monitor Contact volunteers to collect information about transmission. A 3 day course of Azithromycin will be administered on week 6 if colonised.

Drug: Azithromycin Pill

Challenge

EXPERIMENTAL

Challenge volunteers will receive a nasal inoculation containing Bordetella pertussis on Day 0. They will return to the Clinical Research Facility weekly to monitor safety, colonisation and immune responses. A 3 day course of Azithromycin will be administered on week 6 if colonised.

Biological: Bordetella pertussis B1917; Drug: Azithromycin Pill

Interventions

Bordetella pertussis B1917 BIOLOGICAL

The B. pertussis isolate to be used in this human colonisation model is strain B1917, which is representative of current isolates in Europe. The strain, isolated in 2000 from a Dutch patient with B. pertussis disease, expresses Pertactin (PRN), Pertussis Toxin (PT) and Filamentous Haemagglutinin (FHA). This strain has been extensively characterised in the mouse model as well as by proteomics and transcriptomics and has a closed genome available. It is fully sensitive to azithromycin in vitro.

Challenge

Azithromycin Pill DRUG

A 3 day course of azithromycin will be administered to all colonised volunteers at week 6, or sooner if early pertussis disease is suspected

Challenge; Contact

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• Individuals living in the same households as:
• unimmunised or partially immunised children and infants aged \< 1 year
• pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
• immunosuppressed individuals
• frail individuals
• 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:
• unimmunised or partially immunised children and infants aged \< 1 year
• pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
• immunosuppressed individuals
• 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

Sponsors & Collaborators

• University of Southampton: lead

Study Sites (1)

NIHR Clinical Research Facility

Southampton, Hampshire, SO16 6YD, United Kingdom

RECRUITING

MeSH Terms

Conditions

Whooping Cough

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Respiratory Tract Infections; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Central Study Contacts

Robert Read

CONTACT

023 8120 4989; r.c.read@soton.ac.uk

Diane Gbesemete

CONTACT

023 8120 4989; d.gbesemete@soton.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single centre controlled human Bordetella pertussis colonisation study. Intervention: nasal challenge with Bordetella pertussis.

Study Record Dates

• First Submitted: March 7, 2023
• First Posted: May 6, 2023
• Study Start: December 6, 2022
• Primary Completion: December 1, 2025
• Study Completion (Estimated): June 1, 2026
• Last Updated: April 8, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)