Establishing a Controlled Human Infection Model of Pertactin-deficient Bordetella Pertussis

NCT06827470 | Recruiting Phase 1 DMC FDA Drug

• 2 other identifiers: CD230175D30123C17596
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

The overall goal of this study is to establish a PRN-deficient pertussis Controlled Human Infection Model (CHIM) that represents currently circulating isolates, in the context of a North American exposure (vaccination and infection) pedigree.

Conditions

Pertussis (Whooping Cough)

Keywords

Bordetella pertussis; Pertussis; Whooping cough; Controlled human infection model; Human challenge; Phase 1 clinical trial; Immune response

Outcome Measures

Primary Outcomes (1)

• Primary Outcome Measures

  Establish a PRN-deficient pertussis CHIM that identifies the lowest challenge dose that successfully \& safely infects nearly all (≥85%) participants challenged (HID) \& produces the highest achievable rate of symptomatic infection (HSD), including cough, using an adaptive dose response design. This is contingent upon determining each participant's clinical outcome post-challenge to compute the rate of symptomatic infection \& rate of overall infection per dose group, based on outcomes for all participants receiving that dose. As a derived variable, clinical outcomes will be measured/determined using programmed case definitions previously designed to emulate the natural course of early pertussis disease following experimentally induced pertussis infection. Clinical outcome measures include: 1. B. pertussis lab testing of samples (culture, PCR, serology) 2. Clinical assessments (safety bloods, physical exams, DCs, symptom self-reporting).

  Study Day 1 up to Study Day 29

Secondary Outcomes (5)

• Secondary Outcome Measures

  Study Day 1 up to Study Day 29

• Secondary Outcome Measures

  Day 1 up to Study Day 181

• Secondary Outcome Measure

  Time Frame: Day 1 up to Study Day 181

• Secondary Outcome Measures

  Study Day 1 up to Study Day 29

• Secondary Outcome Measure

  Time Frame: Study Day 1 up to Study Day 29

Other Outcomes (2)

• Exploratory Outcome Measures

  Study Day 1 up to Study Day 181

• Exploratory Outcome Measures

  Study Day 1 Up to Study Day 181

Study Arms (5)

Group 1: Dose Number 5 (10^5)

EXPERIMENTAL

Biological: Biological: Bordetella pertussis J820

Group 2: Dose Number 7 (10^6)

EXPERIMENTAL

Biological: Biological: Bordetella pertussis J820

Group 3: Dose Number 9 (10^7)

EXPERIMENTAL

Biological: Biological: Bordetella pertussis J820

Group 4: Dose Number 11 (10^8)

EXPERIMENTAL

Biological: Biological: Bordetella pertussis J820

Group 5: Dose Number 13 (10^9)

EXPERIMENTAL

Biological: Biological: Bordetella pertussis J820

Interventions

Biological: Bordetella pertussis J820 BIOLOGICAL

Intranasal inoculation of Bordetella pertussis J820 in each naris on Day 1 of the study.

Group 1: Dose Number 5 (10^5); Group 2: Dose Number 7 (10^6); Group 3: Dose Number 9 (10^7); Group 4: Dose Number 11 (10^8); Group 5: Dose Number 13 (10^9)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be eligible for the study, each participant must satisfy ALL of the following criteria:
• Age 18-50 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 a cis woman and/or gender divergent person is at risk of becoming pregnant has practiced adequate contraception for 28 days prior to challenge and has a negative pregnancy test on the day before B. pertussis challenge and has agreed to continue adequate contraception until 60 days after inoculation.
• Risk of pregnancy is defined as any individual assigned female at birth or with reproductive capacity who is sexually active with individuals with sperm-producing capabilities. Individuals who have received the following are considered to not have reproductive capacity:
• Documented hysterectomy
• Documented bilateral salpingectomy
• Documented bilateral oophorectomy
• Documented and current bilateral tubal ligation or occlusion
• Credible self-reported history of diagnosed infertility
• Hormone therapy (e.g., testosterone), provided it is administered consistently and medically assessed as sufficient to reduce pregnancy such that ovulation has ceased
• Any other condition, as determined by the Principal Investigator, that would render an individual incapable of becoming pregnant
• 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:

You may not qualify if:

• 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.
• Moderate or severe symptoms of health anxiety, anxiety, and mood symptoms. Self-reported current diagnosis of a major psychiatric illness, including a schizophrenia spectrum disorder, bipolar disorder, posttraumatic stress disorder, obsessive compulsive disorder, substance use, or eating disorder.
• QT prolongation on electrocardiogram (EKG).
• History of everyday smoking/vaping in the last 2 years and/or current smoking/vaping more than once per week.
• Pregnant (known before or established at the time of screening using a urine-based test) or breastfeeding.
• Immunocompromised (with HIV/AIDS-positive or receiving immunosuppressive therapy involving steroids) or with any medical condition or medication that leads to a compromised immune system.
• Positive for hepatitis B or C by blood test.
• 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, including having been exposed to B. pertussis in a Controlled Human Infection Model
• Antibody titer to pertussis toxin \>20 IU/mL (2x the lower limit of quantification (LLOQ)).
• Detection of B. pertussis in nasal samples prior to challenge using culture isolation and/or PCR detection, or detection of other respiratory infection.
• Living or working with (any form of close contact) any of the at-risk/vulnerable groups who are not up to date on their vaccination, specifically children \<1 year of age, pregnant woman who have not yet received their maternal Tdap vaccine, immunocompromised individuals, adults \>65 years of age who have not received a dose of Tdap vaccine within the past 10 years, or other at risk persons, as applicable, up to Day 57.
• Note: Household members whose vaccination is not current will be offered or directed to a pertussis-containing vaccine, as recommended and funded by the Nova Scotia Department of Health and Wellness.

Sponsors & Collaborators

• Dalhousie University: lead
• Centers for Disease Control and Prevention: collaborator

Study Sites (1)

Canadian Center for Vaccinology

Halifax, Nova Scotia, B3K 6R8, Canada

RECRUITING

MeSH Terms

Conditions

Whooping Cough

Condition Hierarchy (Ancestors)

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

Central Study Contacts

Nick Bartlett

CONTACT

902-470-8141; nicholas.bartlett@iwk.nshealth.ca

Hannah Munday

CONTACT

902-470-8141; hannah.munday@iwk.nshealth.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: February 14, 2025
• Study Start: November 24, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): April 30, 2027
• Last Updated: December 4, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)