Establishing a Controlled Human Infection Model of Bordetella Pertussis

NCT05136599 | Completed Phase 1 DMC FDA Drug

• 3 other identifiers: CD2001R34AI14805675D30120C08608
• Study Type: interventional
• Target: 79
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to establish a Controlled Human Infection Model of Bordetella pertussis by determining a reproducible and safe infectious bacterial dose (challenge inoculum) that achieves colonization and mild symptomatic infection in healthy adults.

Conditions

Pertussis

Keywords

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

Outcome Measures

Primary Outcomes (1)

• Number of participants with mild symptoms of early pertussis disease postchallenge

  Mild, Grade 1, symptoms of pertussis are symptoms that do not interfere with everyday activities. They may include malaise, rhinorrhea, sneezing and/or lacrimation, low-grade fever, or cough.

  Day 0 (challenge day) to Day 16

Secondary Outcomes (1)

• Number of participants who demonstrate shedding of Bordetella pertussis postchallenge as determined by positive culture and/or PCR test of nasopharyngeal samples

  Day 1 to Day 14

Study Arms (14)

Study 1 (Dose-identification study), Cohort 1, Dose #3

EXPERIMENTAL

Challenge dose of 10\^4 cfu B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 1 (Dose-identification study), Cohort 2, Dose #5

EXPERIMENTAL

Challenge dose of 10\^5 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 1 (Dose-identification study), Cohort 3, Dose #6

EXPERIMENTAL

Challenge dose of 5 x 10\^5 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 1 (Dose-identification study), Cohort 4, Dose #7

EXPERIMENTAL

Challenge dose of 10\^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 1 (Dose-identification study), Cohort 5, Dose #8

EXPERIMENTAL

Challenge dose of 5 x 10\^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 1 (Dose-identification study), Cohort 6, Dose #9

EXPERIMENTAL

Challenge dose of 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 1 (Dose-identification study), Cohort 7, Dose #9 Repeat

EXPERIMENTAL

Challenge dose of 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 2 (Dose confirmation study), Cohort 8, Dose #9

EXPERIMENTAL

Challenge dose of 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 2 (Dose confirmation study), Cohort 8, Dose #10

EXPERIMENTAL

Challenge dose of 5 x 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 2 (Dose confirmation study), Cohort 9, Dose #9

EXPERIMENTAL

Challenge dose of 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 2 (Dose confirmation study), Cohort 9, Dose #10

EXPERIMENTAL

Challenge dose of 5 x 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 2 (Dose confirmation study), Cohort 10, Dose #8

EXPERIMENTAL

Challenge dose of 5 x 10\^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Study 2 (Dose confirmation study), Cohort 11, Dose #10

EXPERIMENTAL

Challenge dose of 5 x 10\^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Sub-Study (Dose confirmation study), Cohort 11, Dose #11

EXPERIMENTAL

Challenge dose of 10\^8 CFU B. pertussis in 0.2 mL (0.1 mL per naris)

Biological: Bordetella pertussis D420

Interventions

Bordetella pertussis D420 BIOLOGICAL

Intranasal inoculation of Bordetella pertussis D420 in each naris on Day 0 of the study.

Study 1 (Dose-identification study), Cohort 1, Dose #3; Study 1 (Dose-identification study), Cohort 2, Dose #5; Study 1 (Dose-identification study), Cohort 3, Dose #6; Study 1 (Dose-identification study), Cohort 4, Dose #7; Study 1 (Dose-identification study), Cohort 5, Dose #8; Study 1 (Dose-identification study), Cohort 6, Dose #9; Study 1 (Dose-identification study), Cohort 7, Dose #9 Repeat; Study 2 (Dose confirmation study), Cohort 10, Dose #8; Study 2 (Dose confirmation study), Cohort 11, Dose #10; Study 2 (Dose confirmation study), Cohort 8, Dose #10; Study 2 (Dose confirmation study), Cohort 8, Dose #9; Study 2 (Dose confirmation study), Cohort 9, Dose #10; Study 2 (Dose confirmation study), Cohort 9, Dose #9; Sub-Study (Dose confirmation study), Cohort 11, Dose #11

Eligibility Criteria

• Age: 18 Years - 40 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 18-40 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 childbearing potential and heterosexually active, 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. 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
• A premenopausal woman who has at least one of the following is considered not of childbearing potential:
• Documented hysterectomy
• Documented bilateral salpingectomy

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.
• 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 \>20 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 up to Day 56 post-challenge. Note: Household members whose vaccination is not current will be offered a pertussis-containing vaccine, as recommended and funded by the Nova Scotia Department of Health and Wellness.
• Living or working with (any form of close contact) any of the at-risk/vulnerable groups (children \<1 year of age, pregnant woman who have not yet received their maternal Tdap vaccine, immunocompromised individuals, anyone not current in their pertussis immunization, or adults \>65 years of age who have not received a dose of Tdap vaccine within the past 10 years) up to Day 56 post-challenge.

Sponsors & Collaborators

• Dalhousie University: lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator
• Centers for Disease Control and Prevention: collaborator
• Vanderbilt University Medical Center: collaborator

Study Sites (1)

Canadian Center for Vaccinology

Halifax, Nova Scotia, B3K 6R8, Canada

Location

Related Links

• Canadian Center for Vaccinology Challenge Unit home page
• Canadian Center for Vaccinology home page

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

Study Officials

• Scott A. Halperin, MD

  Dalhousie University

  PRINCIPAL INVESTIGATOR

Study Design

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

Model Details: The clinical trial will be conducted as two dependent studies. The first study is a dose identification study to determine the HID70-90 endpoint, which is the dose that induces pertussis mild symptomatic/clinical infection among 70%-90% of the volunteers inoculated with that dose. The second study and sub-study are HID70-90 dose confirmation studies to verify and confirm that the infectious endpoint has been reached to establish the pertussis CHIM.

Study Record Dates

• First Submitted: November 2, 2021
• First Posted: November 29, 2021
• Study Start: January 28, 2022
• Primary Completion: March 14, 2025
• Study Completion: March 14, 2025
• Last Updated: August 13, 2025

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)