Establishing a Controlled Human Infection Model of Bordetella Pertussis
Pertussis
About this trial
This is an interventional other trial for Pertussis focused on measuring Bordetella pertussis, Pertussis, Whooping cough, Controlled human infection model, Human challenge, Phase 1 clinical trial, Immune response
Eligibility Criteria
Inclusion Criteria:
To be eligible for the study, each participant must satisfy ALL of the following criteria:
- Age 18-40 years, inclusive.
- Good general health status, as determined by history and physical examination conducted no longer than 30 days prior to the challenge.
- Participants who, in the opinion of the Investigator, can and will comply with the requirements of the protocol (e.g., complete Diary Cards, return for follow-up visits).
- Written informed consent obtained from the participant.
If female of child-bearing potential and heterosexually active, has practiced adequate contraception for 28 days prior to challenge and has a negative pregnancy test on the day of B. pertussis challenge and has agreed to continue adequate contraception until 60 days after inoculation. Adequate contraception is defined as a contraceptive method with a failure rate of <1% per year when used consistently and correctly and, when applicable, in accordance with the product label. Examples include the following:
- Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation: oral, intravaginal, or transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation: oral, injectable, or implantable
- Intra-uterine device (IUD) with or without hormonal release
- Vasectomized partner, provided that this is the participant's sole partner and that he has received a medical assessment of the surgical success
- Credible self-reported history of heterosexual abstinence for at least 28 days prior to challenge
- Female partner
Exclusion Criteria:
Participants with ANY of the following criteria at the time of screening will be excluded:
- Underlying chronic medical condition requiring ongoing follow-up and monitoring by a physician (e.g., diabetes, seizure disorder).
- Underlying cardiac and/or pulmonary disease including hypertension, angina, prior myocardial infarction, asthma, emphysema, chronic bronchitis, and pulmonary tuberculosis.
- QT prolongation on electrocardiogram (EKG).
- Current cigarette smoker or cigarette smoker within the previous 5 years.
- Pregnant (known before or established at the time of screening using a urine-based test) or breastfeeding.
- Immunocompromised (HIV/AIDS-positive or receiving immunosuppressive therapy involving steroids).
- Positive for hepatitis B or C.
- Vaccinated against pertussis within previous 5 years and/or >7 cumulative doses from infancy to date of screening.
- Reported history of laboratory-confirmed pertussis infection.
- Antibody titer to pertussis toxin >10 EU/mL (2x the lower limit of quantification (LLOQ)).
- Nasopharyngeal detection of B. pertussis prior to challenge using culture isolation and/or PCR detection, or detection of other respiratory infection.
- Living with young children (<1 year of age) or with any household member not current in their pertussis immunization. (Note: Household members whose vaccination is not current will be offered a pertussis-containing vaccine, as recommended and funded by Nova Scotia Department of Health and Wellness.)
- Known allergy to macrolides including azithromycin or erythromycin, history of Clostridium difficile within last 2 months.
- Taking any antibiotic currently or within the previous 2 weeks.
- Currently taking terfenadine, astemizole, theophylline, or cimetidine.
- Recent (within 6 months) nasal or sinus surgery, recent use of intranasal steroids (4 weeks), or diagnosis with nasal polyps.
- Receipt of any investigational drug within 6 months.
- Receipt of any authorized (approved or investigational) vaccines within 2 weeks of study immunization.
- Receipt of experimental SARS-CoV-2/COVID-19 vaccine(s) at any time prior to or during the study.
- Known current or previous laboratory-confirmed SARS-CoV-1 or SARS-CoV-2 infection, as documented by a positive PCR test from a nasal swab or known positive serology.
- Head trauma (e.g., fracture of the cribriform plate) within 1 year of screening.
- Any other finding that the Investigator considers will make the participant unsuitable for the study or unable to comply with the study requirements.
Sites / Locations
- Canadian Center for VaccinologyRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm 7
Arm 8
Arm 9
Arm 10
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Experimental
Study 1 (Dose-identification study), Dose 1
Study 1 (Dose-identification study), Dose 2
Study 1 (Dose-identification study), Dose 3
Study 1 (Dose-identification study), Dose 4
Study 1 (Dose-identification study), Dose 5
Study 1 (Dose-identification study), Dose 6
Study 1 (Dose-identification study), Dose 7
Study 1 (Dose-identification study), Dose 8
Study 1 (Dose-identification study), Dose 9
Study 1 (Dose-identification study), Dose 10
Challenge dose of 10^3 cfu B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 5 x 10^3 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 10^4 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 5 x 10^4 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 10^5 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 5 x 10^5 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 10^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 5 x 10^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 10^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Challenge dose of 5 x 10^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)