Whooping CoughPeriscopeNCT03751514
Bordetella Pertussis Colonisation Challenge Study
A study testing Bordetella Pertussis B1917, Azithromycin 500 mg and Sterile Saline in people with Whooping Cough, run by University of Southampton at 1 site in United Kingdom.
Trial summary
This is a prospective controlled human challenge study consisting of two phases; Phase A: Development of a B. pertussis human challenge model; pilot to establish the standard inoculum Phase B: Development of a modified B. pertussis human challenge model Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Whooping Cough
- What is being tested?
- Bordetella Pertussis B1917, Azithromycin 500 mg and Sterile Saline
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 22 May 2017to 2 Feb 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 45 years inclusive on the day of screening
- Fully conversant in the English language
- Able to communicate easily by both mobile telephone and text messaging
- Able and willing (in the investigator's opinion) to comply with all study requirements
- Written informed consent to participate in the trial
- Willingness to take a curative antibiotic regimen after inoculation with B. pertussis according to the study protocol
- Agreement to be admitted to the National Institute for Health Research (NIHR)-Clinical research facility (CRF) Southampton for 17 days for phase A (from inoculation until two days after the eradication therapy is given) and for the duration necessary for phase B, depending on phase A results
- Able to answer all questions on the informed consent quiz correctly
Who cannot join
- Individuals who have inviolable commitments within 3 months of discharge from the inpatient phase of the study to make 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
- Individuals who have household contacts working 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
Show all 21Show fewer
- Phase A only: Volunteers will be excluded from this study if they have evidence of recent exposure to B. pertussis, as determined by anti-PT IgG ELISA (>20 IU/mL)
- B. pertussis detected on nasopharyngeal swab taken before the challenge
- Individuals who have a signs of a current 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 a history of never being vaccinated against B. pertussis
- Current smokers defined as having had a cigarette/cigar in the last week.
- 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 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
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
NIHR Wellcome Trust Clinical Research Facility, Southampton General Hospital
Southampton, Hampshire, SO16 6YD
Hans De Graaf, MRCPCH, 02381204989 ext. 4989, H.De-Graaf@soton.ac.uk
Sara Hughes, MPhil, 02381203853 ext. 3853, Sara.Hughes@uhs.nhs.uk
About this study
Official title: A Human Controlled Infection Study to Establish a Safe, Reproducible and Practical Human Bordetella Pertussis Colonisation Model for the Identification of Correlates of Protection Against Colonisation (BPCCS)
This is a prospective controlled human challenge study consisting of two phases; Phase A: Development of a B. pertussis human challenge model; pilot to establish the standard inoculum Phase B: Development of a modified B. pertussis human challenge model
Read the detailed description
This study is part of work package 2 of the Periscope consortium. The Periscope consortium brings together internationally renowned scientists with many years of experience in B. pertussis research, clinical trials, bioinformatics, immunology and public health to promote scientific and technological innovation in pertussis vaccine development and to foster the creation of a laboratory and scientific network that facilitates the testing and helps expedite the development of novel pertussis vaccines in Europe. This study, the development of a human challenge model for B. pertussis, is one of the models that will accelerate the development and registration of novel pertussis vaccines and will provide samples for studies performed within the network.
This is a prospective controlled human challenge study consisting of two phases; Phase A: Development of a B. pertussis human challenge model; pilot to establish the standard inoculum The first aim of phase A is to determine a 'standard inoculum' (SI), which results in safe colonisation of 70% of volunteers. This level of colonisation of 70% has been selected so that baseline immune profiles of individuals who are, or are not colonised following challenge can be assessed and biomarkers of protection from colonisation identified. It is acknowledged that for the future use of the human challenge model for efficacy evaluation of experimental vaccine candidates, it would be optimal if the percentage of subjects successfully colonised were at least 70%. The SI will be identified in a dose escalating or de-escalating experiment commencing at 103 colony forming units B. pertussis administered intranasally. Each group of 5 volunteers will be sequentially inoculated at half log-fold increasing/decreasing doses until the endpoint is reached. The experiment will be continued until the SI yields 10 subjects who are colonised at day 14. Volunteers will be screened to exclude those with evidence of recent B. pertussis infection using anti-pertussis toxin (PT) immunoglobulin G (IgG) ELISA as evidence to allow evaluation of seroconversion. Following the challenge chemical, haematological and clinical parameters will be monitored and nasal swab samples will be cultured at regular intervals to assure safety of the volunteers and to identify the presence of B. pertussis. At day 14 after the challenge, or at the onset of symptoms, whichever occurs soonest, eradication therapy in the form of azithromycin 500 mg once a day for 3 days will be given. Further mucosal and blood samples will be taken over the follow up period of one year.
The second aim of phase A is to identify the 'colonisation period'; the earliest day after inoculation at which colonisation of the nasopharynx (as detected by culture) is observed in 100% of those volunteers who show seroconversion at day 28. This time period will be used to establish the length of participation required from volunteers in future studies. The colonisation period will be deemed biologically relevant if B. pertussis specific mucosal and systemic antibodies are elicited in people who are colonised for the colonisation period. A quantitative PCR assay to detect B. pertussis in nasopharyngeal samples will be evaluated to determine if this can provide more rapid information in addition to culture.
The third aim of phase A is to access environmental shedding of B. pertussis following nasal inoculation of healthy volunteers with B. pertussis. These shedding results will used to determine the length of admission and isolation in phase B. The shedding of B. pertussis by challenged volunteers will be assessed using personal aerosol samplers and environmental sampling. Efficacy of eradication therapy will be assessed.
Phase B: Development of a modified B. pertussis human challenge model In phase B the pilot study data from phase A will be used to design a more practical model, if possible conducted partially in an outpatient setting, which will be conditional on safety and transmission evidence. The final protocol for phase B will be presented as a protocol amendment, because it will be based on the standard inoculum and colonisation period identified in Phase A.
Volunteers in phase B will not be preselected to exclude those with evidence of recent B. pertussis infection. The standard inoculum determined in phase A will be used for all volunteers and eradication therapy will be given after the colonisation period based on the data of phase A. Approximately 30 individuals will receive the intranasal SI and as control group approximately 15 individuals will receive intranasal sham. Both groups will be treated with azithromycin for three days at the end of the colonisation period.
Aims:
- To confirm that the following parameters of the model in phase B are similar to that seen in phase A:
- Volunteer safety
- Colonisation rate
- Colonisation period
- Genetic/expression changes in B. pertussis during challenge
- Environmental shedding
- Efficacy of eradication therapy
- To compare the pattern of detection of B. pertussis in nasopharyngeal samples by qPCR to that seen in phase A.
- To assess B. pertussis-specific immunity before and after inoculating healthy volunteers with B. pertussis, comparing the data from successfully colonised participants with the data from those not colonised and the control group.
- Conditions
- Whooping Cough
- Being tested
- Bordetella Pertussis B1917, Azithromycin 500 mg, Sterile Saline
- Keywords
- Bordetella Pertussis
- Medical subject headings
- Whooping Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bordetella Pertussis B1917Biological
Also called Whooping cough bacteria
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 Prn, 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.
Providing there are no safety concerns the standard inoculum (SI) will be identified in a dose escalating or de-escalating experiment commencing at 103 colony forming units administered intranasally.
Azithromycin 500 mgDrug
Also called Zithromax
To ameliorate risk of transmission of B. pertussis B1917 to the environment and household contacts, Azithromycin 500 mg once a day for 3 days will be given to eradicate colonisation with B. pertussis. The inoculum strain is fully sensitive to this antibiotic. Previous studies show that azithromycin eradicates colonisation in 97% of people in 48 hours.
Sterile SalineOther
Also called Sham
To compare against B. pertussis, some volunteers will be enrolled onto the Sham arm. These volunteers will not receive B. pertussis but instead be given sterile saline
| Study group | Role | What they receive |
|---|---|---|
| Phase A - SI | Experimental | Phase A aims to determine a 'standard inoculum' dose (SI), which results in safe colonisation of 70% of volunteers.
The SI will be identified in a dose escalating or de-escalating experiment commencing at 10-3 colony forming units B. pertussis administered intranasally. Each group of volunteers will be inoculated at half log-fold increasing/decreasing doses until the endpoint is reached. The experiment will be continued until the SI yields 10 subjects who are colonised at day 14.
Intervention to be administered: Bordetella Pertussis B1917 Receives: Biological: Bordetella Pertussis B1917; Drug: Azithromycin 500 mg |
| Phase B Inoculum | Experimental | Phase B, using study data from phase A, will be used to design a more practical model - if possible conducted partially in an outpatient setting, which will be conditional on safety and transmission evidence. The final protocol for phase B will be presented as a protocol amendment, it will be based on the SI and colonisation period identified in Phase A.
The SI determined in phase A will be used for all volunteers and eradication therapy will be given after the colonisation period based on the data of phase A. Approximately 30 individuals will receive the intranasal SI and will be treated with azithromycin for three days at the end of the colonisation period.
Intervention to be administered: Bordetella Pertussis B1917 Receives: Biological: Bordetella Pertussis B1917; Drug: Azithromycin 500 mg |
| Phase B Sham | Experimental | Phase B, using study data from phase A, will be used to design a more practical model - if possible conducted partially in an outpatient setting, which will be conditional on safety and transmission evidence.
Approximately 15 individuals will not receive the Bordetella Pertussis B1917, instead they will be given an intranasal sham of sterile saline and will be treated with azithromycin 500mg for three days at the end of the 'colonisation' period. Receives: Drug: Azithromycin 500 mg; Other: Sterile Saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
Phase A - Inoculum Dose Determination
The inoculum dose required to cause the safe colonisation of 70% of volunteers who are challenged. A starting inoculum of 10^3 bacteria will be used and incrementally increased until microbiologically proven Bp infection by positive culture of Bp from a nasopharyngeal swab (CFU/mL). Swabs are taken between time points day 0 and day 14 and compare with baseline.
Measured: Up to volunteer visit Day 14
Secondary outcomes (11)
Phase A and B - Immune Responses to exposure to Bordetella pertussis
Measure the antibody response (IU/L) of volunteers who receive the inoculum against the immune responses of those that receive the sham treatment.
Measured: Up to volunteer visit Week 52
Phase A - Accuracy of Inoculum Dosing Evaluation
Measurement of the challenge dose (cfu/mL) actually given to volunteers by counting CFUs after culturing. This is done by culturing the remaining inoculum which has been given to the volunteers. Results are then compared with the prescribed dose (cfu/mL).
Measured: Up to volunteer visit Day 7
Phase A and B - Number of participants with Bp exposure-related adverse events as assessed by study specific adverse event grading system based on CTCAE v4.0
After inoculation with Bordetella pertussis, participants will be admitted in the research unit to monitor adverse events closely.
Measured: Up to volunteer visit Day 365
Phase A - Earliest Timepoint for Colonisation of the Nasopharynx
The earliest day after inoculation at which colonisation of the nasopharynx (as detected by culture) is observed in 100% of those volunteers who subsequently seroconvert at day 28. Colonisation will be detected by positive culture of Bp from a nasopharyngeal swab taken between timepoints day 0 and 14
Measured: Up to volunteer visit Day 14
Phase A and B - Bacterial Dynamics after Challenge
Microbiological assays to detect and characterise Bp after challenge in nasopharyngeal swabs (culture and qPCR), nasal wash (culture including semi-quantitative method using cfu count/mL, and precision quantification with qPCR)and sequencing of isolates
Measured: Up to volunteer visit Day 14
Phase A and B - Bacterial Dynamics after Challenge by culture
Bp colonisation will be measured in nasopharyngeal swabs, nasal wash and throat swabs by culture using cfu count/mL
Measured: Up to volunteer visit Day 14
Phase A and B - Bacterial Dynamics after Challenge by PCR
Bp colonisation will be measured in nasopharyngeal swabs, nasal wash and throat swabs by culture using cfu count/mL
Measured: Up to volunteer visit Day 14
Phase A - Environmental shedding of Bp
Air and mask samples will be collected of volunteers and cultured. Results will be expressed as cfu count
Measured: Day 0-16
Phase A & B - Immune Response in nasal wash to Challenge
Immunological laboratory assays to measure innate, humoral, cell-mediated and mucosal responses to challenge in nasal washes.
Measured: Up to volunteer visit Week 52
Phase A & B - Human Immune Response to Challenge in Saliva
Antibody responses to challenge in saliva will be measured (Bp specific Immunoglobulin A (IgA) (IU/mL))
Measured: Up to volunteer visit Week 52
Phase A & B - Correlation of qPCR results with Culture Results after Challenge
Comparison of qPCR results with culture results after challenge: Microbiological assays in nasopharyngeal swabs and nasal washes (culture, qPCR) taken between day 0 and 16
Measured: Up to Day 16
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2018
- Study start22 May 2017
- Primary completion2 Feb 2021 (estimated)
- Study completion2 Feb 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Whooping CoughStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Model description
- Human challenge study
- Masking
- None (open label)
- Enrolment
- 80 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southampton
- Sponsor type
- University, hospital or other
- Collaborators
- Public Health England, University Hospital Southampton NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Robert C Read, MB MD FRCP, Principal investigator, University of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03751514
- Sponsor's protocol ID
- RHM MED1396
- Other IDs
- 17/SC/0006
- Acronym
- Periscope
- Status last verified
- Feb 2020
- First submitted
- 15 Aug 2017
- Last updated
- 27 Feb 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
de Graaf H, Gbesemete DF, Hill AR, Froberg J, Ibrahim MM, Dale AP, Laver JR, Gorringe AR, Faust SN, Kester KE, Buisman AM, Berbers GAM, Brummelman J, van Els CACM, Eleveld MJ, Diavatopoulos DA, Read RC. Safety, colonisation kinetics, transmissibility, and immune correlates of protection in healthy adults inoculated with Bordetella pertussis in England: a single-centre, open-label, phase 1, controlled human infection study. Lancet Microbe. 2026 Apr;7(4):101313. doi: 10.1016/j.lanmic.2025.101313. Epub 2026 Mar 23.
PubMed 41887240Diks AM, de Graaf H, Teodosio C, Groenland RJ, de Mooij B, Ibrahim M, Hill AR, Read RC, van Dongen JJ, Berkowska MA; IMI-2 PERISCOPE Consortium. Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge. J Clin Invest. 2023 Mar 1;133(5):e163121. doi: 10.1172/JCI163121.
PubMed 36649086de Graaf H, Ibrahim M, Hill AR, Gbesemete D, Vaughan AT, Gorringe A, Preston A, Buisman AM, Faust SN, Kester KE, Berbers GAM, Diavatopoulos DA, Read RC. Controlled Human Infection With Bordetella pertussis Induces Asymptomatic, Immunizing Colonization. Clin Infect Dis. 2020 Jul 11;71(2):403-411. doi: 10.1093/cid/ciz840.
PubMed 31562530
Study at a glance
From the registry record, last updated by the sponsor on 27 Feb 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Human Controlled Infection Study to Establish a Safe, Reproducible and Practical Human Bordetella Pertussis Colonisation Model for the Identification of Correlates of Protection Against Colonisation (BPCCS)
- ClinicalTrials.gov ID
- NCT03751514
- Acronym / sponsor ID
- Periscope / RHM MED1396
- Conditions
- Whooping Cough
- Keywords
- Bordetella Pertussis
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- University of SouthamptonUniversity, hospital or other
- Collaborators
- Public Health England, University Hospital Southampton NHS Foundation Trust
- Study start
- 22 May 2017 (actual)
- Primary completion
- 2 Feb 2021 (estimated)
- Study completion
- 2 Feb 2021 (estimated)
- First posted
- 23 Nov 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a prospective controlled human challenge study consisting of two phases; Phase A: Development of a B. pertussis human challenge model; pilot to establish the standard inoculum Phase B: Development of a modified B. pertussis human challenge model
Detailed description
This study is part of work package 2 of the Periscope consortium. The Periscope consortium brings together internationally renowned scientists with many years of experience in B. pertussis research, clinical trials, bioinformatics, immunology and public health to promote scientific and technological innovation in pertussis vaccine development and to foster the creation of a laboratory and scientific network that facilitates the testing and helps expedite the development of novel pertussis vaccines in Europe. This study, the development of a human challenge model for B. pertussis, is one of the models that will accelerate the development and registration of novel pertussis vaccines and will provide samples for studies performed within the network.
This is a prospective controlled human challenge study consisting of two phases; Phase A: Development of a B. pertussis human challenge model; pilot to establish the standard inoculum The first aim of phase A is to determine a 'standard inoculum' (SI), which results in safe colonisation of 70% of volunteers. This level of colonisation of 70% has been selected so that baseline immune profiles of individuals who are, or are not colonised following challenge can be assessed and biomarkers of protection from colonisation identified. It is acknowledged that for the future use of the human challenge model for efficacy evaluation of experimental vaccine candidates, it would be optimal if the percentage of subjects successfully colonised were at least 70%. The SI will be identified in a dose escalating or de-escalating experiment commencing at 103 colony forming units B. pertussis administered intranasally. Each group of 5 volunteers will be sequentially inoculated at half log-fold increasing/decreasing doses until the endpoint is reached. The experiment will be continued until the SI yields 10 subjects who are colonised at day 14. Volunteers will be screened to exclude those with evidence of recent B. pertussis infection using anti-pertussis toxin (PT) immunoglobulin G (IgG) ELISA as evidence to allow evaluation of seroconversion. Following the challenge chemical, haematological and clinical parameters will be monitored and nasal swab samples will be cultured at regular intervals to assure safety of the volunteers and to identify the presence of B. pertussis. At day 14 after the challenge, or at the onset of symptoms, whichever occurs soonest, eradication therapy in the form of azithromycin 500 mg once a day for 3 days will be given. Further mucosal and blood samples will be taken over the follow up period of one year.
The second aim of phase A is to identify the 'colonisation period'; the earliest day after inoculation at which colonisation of the nasopharynx (as detected by culture) is observed in 100% of those volunteers who show seroconversion at day 28. This time period will be used to establish the length of participation required from volunteers in future studies. The colonisation period will be deemed biologically relevant if B. pertussis specific mucosal and systemic antibodies are elicited in people who are colonised for the colonisation period. A quantitative PCR assay to detect B. pertussis in nasopharyngeal samples will be evaluated to determine if this can provide more rapid information in addition to culture.
The third aim of phase A is to access environmental shedding of B. pertussis following nasal inoculation of healthy volunteers with B. pertussis. These shedding results will used to determine the length of admission and isolation in phase B. The shedding of B. pertussis by challenged volunteers will be assessed using personal aerosol samplers and environmental sampling. Efficacy of eradication therapy will be assessed.
Phase B: Development of a modified B. pertussis human challenge model In phase B the pilot study data from phase A will be used to design a more practical model, if possible conducted partially in an outpatient setting, which will be conditional on safety and transmission evidence. The final protocol for phase B will be presented as a protocol amendment, because it will be based on the standard inoculum and colonisation period identified in Phase A.
Volunteers in phase B will not be preselected to exclude those with evidence of recent B. pertussis infection. The standard inoculum determined in phase A will be used for all volunteers and eradication therapy will be given after the colonisation period based on the data of phase A. Approximately 30 individuals will receive the intranasal SI and as control group approximately 15 individuals will receive intranasal sham. Both groups will be treated with azithromycin for three days at the end of the colonisation period.
Aims:
- To confirm that the following parameters of the model in phase B are similar to that seen in phase A:
- Volunteer safety
- Colonisation rate
- Colonisation period
- Genetic/expression changes in B. pertussis during challenge
- Environmental shedding
- Efficacy of eradication therapy
- To compare the pattern of detection of B. pertussis in nasopharyngeal samples by qPCR to that seen in phase A.
- To assess B. pertussis-specific immunity before and after inoculating healthy volunteers with B. pertussis, comparing the data from successfully colonised participants with the data from those not colonised and the control group.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Human challenge study
| Arm | Type | Receives |
|---|---|---|
| Phase A - SI | Experimental | Biological: Bordetella Pertussis B1917, Drug: Azithromycin 500 mgPhase A aims to determine a 'standard inoculum' dose (SI), which results in safe colonisation of 70% of volunteers. The SI will be identified in a dose escalating or de-escalating experiment commencing at 10-3 colony forming units B. pertussis administered intranasally. Each group of volunteers will be inoculated at half log-fold increasing/decreasing doses until the endpoint is reached. The experiment will be continued until the SI yields 10 subjects who are colonised at day 14. Intervention to be administered: Bordetella Pertussis B1917 |
| Phase B Inoculum | Experimental | Biological: Bordetella Pertussis B1917, Drug: Azithromycin 500 mgPhase B, using study data from phase A, will be used to design a more practical model - if possible conducted partially in an outpatient setting, which will be conditional on safety and transmission evidence. The final protocol for phase B will be presented as a protocol amendment, it will be based on the SI and colonisation period identified in Phase A. The SI determined in phase A will be used for all volunteers and eradication therapy will be given after the colonisation period based on the data of phase A. Approximately 30 individuals will receive the intranasal SI and will be treated with azithromycin for three days at the end of the colonisation period. Intervention to be administered: Bordetella Pertussis B1917 |
| Phase B Sham | Experimental | Drug: Azithromycin 500 mg, Other: Sterile SalinePhase B, using study data from phase A, will be used to design a more practical model - if possible conducted partially in an outpatient setting, which will be conditional on safety and transmission evidence. Approximately 15 individuals will not receive the Bordetella Pertussis B1917, instead they will be given an intranasal sham of sterile saline and will be treated with azithromycin 500mg for three days at the end of the 'colonisation' period. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Healthy adults aged 18 to 45 years inclusive on the day of screening
- Fully conversant in the English language
- Able to communicate easily by both mobile telephone and text messaging
- Able and willing (in the investigator's opinion) to comply with all study requirements
- Written informed consent to participate in the trial
Key exclusion criteria (21 listed)
- Individuals who have inviolable commitments within 3 months of discharge from the inpatient phase of the study to make contact with:
- Individuals who have household contacts working with
- Phase A only: Volunteers will be excluded from this study if they have evidence of recent exposure to B. pertussis, as determined by anti-PT IgG ELISA (>20 IU/mL)
- B. pertussis detected on nasopharyngeal swab taken before the challenge
- Individuals who have a signs of a current infection at the time of inoculation with B. pertussis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bordetella Pertussis B1917Also: Whooping cough bacteriaThe 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 Prn, 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. Providing there are no safety concerns the standard inoculum (SI) will be identified in a dose escalating or de-escalating experiment commencing at 103 colony forming units administered intranasally. | Biological | Phase A - SI, Phase B Inoculum |
| Azithromycin 500 mgAlso: ZithromaxTo ameliorate risk of transmission of B. pertussis B1917 to the environment and household contacts, Azithromycin 500 mg once a day for 3 days will be given to eradicate colonisation with B. pertussis. The inoculum strain is fully sensitive to this antibiotic. Previous studies show that azithromycin eradicates colonisation in 97% of people in 48 hours. | Drug | Phase A - SI, Phase B Inoculum, Phase B Sham |
| Sterile SalineAlso: ShamTo compare against B. pertussis, some volunteers will be enrolled onto the Sham arm. These volunteers will not receive B. pertussis but instead be given sterile saline | Other | Phase B Sham |
Primary outcome
Phase A - Inoculum Dose Determination
Time frame: Up to volunteer visit Day 14
The inoculum dose required to cause the safe colonisation of 70% of volunteers who are challenged. A starting inoculum of 10^3 bacteria will be used and incrementally increased until microbiologically proven Bp infection by positive culture of Bp from a nasopharyngeal swab (CFU/mL). Swabs are taken between time points day 0 and day 14 and compare with baseline.
11 secondary outcomes
Phase A and B - Immune Responses to exposure to Bordetella pertussis
Time frame: Up to volunteer visit Week 52
Phase A - Accuracy of Inoculum Dosing Evaluation
Time frame: Up to volunteer visit Day 7
Phase A and B - Number of participants with Bp exposure-related adverse events as assessed by study specific adverse event grading system based on CTCAE v4.0
Time frame: Up to volunteer visit Day 365
Phase A - Earliest Timepoint for Colonisation of the Nasopharynx
Time frame: Up to volunteer visit Day 14
Phase A and B - Bacterial Dynamics after Challenge
Time frame: Up to volunteer visit Day 14
Phase A and B - Bacterial Dynamics after Challenge by culture
Time frame: Up to volunteer visit Day 14
Phase A and B - Bacterial Dynamics after Challenge by PCR
Time frame: Up to volunteer visit Day 14
Phase A - Environmental shedding of Bp
Time frame: Day 0-16
Phase A & B - Immune Response in nasal wash to Challenge
Time frame: Up to volunteer visit Week 52
Phase A & B - Human Immune Response to Challenge in Saliva
Time frame: Up to volunteer visit Week 52
Phase A & B - Correlation of qPCR results with Culture Results after Challenge
Time frame: Up to Day 16
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2020.
- Derived from this study: PubMed 41887240de Graaf H, Gbesemete DF, Hill AR, Froberg J, Ibrahim MM, Dale AP, Laver JR, Gorringe AR, Faust SN, Kester KE, Buisman AM, Berbers GAM, Brummelman J, van Els CACM, Eleveld MJ, Diavatopoulos DA, Read RC. Safety, colonisation kinetics, transmissibility, and immune correlates of protection in healthy adults inoculated with Bordetella pertussis in England: a single-centre, open-label, phase 1, controlled human infection study. Lancet Microbe. 2026 Apr;7(4):101313. doi: 10.1016/j.lanmic.2025.101313. Epub 2026 Mar 23.
- Derived from this study: PubMed 36649086Diks AM, de Graaf H, Teodosio C, Groenland RJ, de Mooij B, Ibrahim M, Hill AR, Read RC, van Dongen JJ, Berkowska MA; IMI-2 PERISCOPE Consortium. Distinct early cellular kinetics in participants protected against colonization upon Bordetella pertussis challenge. J Clin Invest. 2023 Mar 1;133(5):e163121. doi: 10.1172/JCI163121.
- Derived from this study: PubMed 31562530de Graaf H, Ibrahim M, Hill AR, Gbesemete D, Vaughan AT, Gorringe A, Preston A, Buisman AM, Faust SN, Kester KE, Berbers GAM, Diavatopoulos DA, Read RC. Controlled Human Infection With Bordetella pertussis Induces Asymptomatic, Immunizing Colonization. Clin Infect Dis. 2020 Jul 11;71(2):403-411. doi: 10.1093/cid/ciz840.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert C Read, MB MD FRCP principal investigator
University of Southampton
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bordetella Pertussis B1917, Azithromycin 500 mg and Sterile Saline in people with Whooping Cough, run by University of Southampton at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 27 Feb 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Hans de Graaf, MRCPCH (02381204989 ext. 4989, H.De-Graaf@soton.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Phase A - Inoculum Dose Determination (time frame: Up to volunteer visit Day 14). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03751514, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2020.