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Establishing a Controlled Human Infection Model of Bordetella Pertussis

Primary Purpose

Pertussis

Status
Recruiting
Phase
Phase 1
Locations
Canada
Study Type
Interventional
Intervention
Bordetella pertussis D420
Sponsored by
Dalhousie University
About
Eligibility
Locations
Arms
Outcomes
Full info

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

18 Years - 40 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

To be eligible for the study, each participant must satisfy ALL of the following criteria:

  1. Age 18-40 years, inclusive.
  2. Good general health status, as determined by history and physical examination conducted no longer than 30 days prior to the challenge.
  3. 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).
  4. Written informed consent obtained from the participant.
  5. 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:

  1. Underlying chronic medical condition requiring ongoing follow-up and monitoring by a physician (e.g., diabetes, seizure disorder).
  2. Underlying cardiac and/or pulmonary disease including hypertension, angina, prior myocardial infarction, asthma, emphysema, chronic bronchitis, and pulmonary tuberculosis.
  3. QT prolongation on electrocardiogram (EKG).
  4. Current cigarette smoker or cigarette smoker within the previous 5 years.
  5. Pregnant (known before or established at the time of screening using a urine-based test) or breastfeeding.
  6. Immunocompromised (HIV/AIDS-positive or receiving immunosuppressive therapy involving steroids).
  7. Positive for hepatitis B or C.
  8. Vaccinated against pertussis within previous 5 years and/or >7 cumulative doses from infancy to date of screening.
  9. Reported history of laboratory-confirmed pertussis infection.
  10. Antibody titer to pertussis toxin >10 EU/mL (2x the lower limit of quantification (LLOQ)).
  11. Nasopharyngeal detection of B. pertussis prior to challenge using culture isolation and/or PCR detection, or detection of other respiratory infection.
  12. 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.)
  13. Known allergy to macrolides including azithromycin or erythromycin, history of Clostridium difficile within last 2 months.
  14. Taking any antibiotic currently or within the previous 2 weeks.
  15. Currently taking terfenadine, astemizole, theophylline, or cimetidine.
  16. Recent (within 6 months) nasal or sinus surgery, recent use of intranasal steroids (4 weeks), or diagnosis with nasal polyps.
  17. Receipt of any investigational drug within 6 months.
  18. Receipt of any authorized (approved or investigational) vaccines within 2 weeks of study immunization.
  19. Receipt of experimental SARS-CoV-2/COVID-19 vaccine(s) at any time prior to or during the study.
  20. 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.
  21. Head trauma (e.g., fracture of the cribriform plate) within 1 year of screening.
  22. 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

Arm Type

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Experimental

Arm Label

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

Arm Description

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)

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Number of participants who demonstrate shedding of Bordetella pertussis postchallenge as determined by positive culture and/or PCR test of nasopharyngeal samples
The presence of B. pertussis is detected by positive culture (i.e., presence of any B. pertussis colonies) of nasopharyngeal samples. It is also detected by a positive PCR (polymerase chain reaction) test of nasopharyngeal samples. Both methods are used in this study; a positive result in either culture and/or PCR test demonstrates shedding of B. pertussis.

Full Information

First Posted
November 2, 2021
Last Updated
June 21, 2023
Sponsor
Dalhousie University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Centers for Disease Control and Prevention, Vanderbilt University Medical Center
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1. Study Identification

Unique Protocol Identification Number
NCT05136599
Brief Title
Establishing a Controlled Human Infection Model of Bordetella Pertussis
Official Title
Open-label, Phase 1, Dose-escalation Clinical Trial to Establish a Controlled Human Infection Model by Determining the Optimal and Safe Bordetella Pertussis Dose That Induces Mild Symptomatic Infection and Colonization in Healthy Adults
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
January 28, 2022 (Actual)
Primary Completion Date
January 2024 (Anticipated)
Study Completion Date
January 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Dalhousie University
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID), Centers for Disease Control and Prevention, Vanderbilt University Medical Center

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.
Detailed Description
This is a single-center trial to develop a Bordetella pertussis Controlled Human Infection Model (CHIM) using a two-study approach: the first study is a human infectious dose 70%-90% (HID70-90) identification study, and the second an HID70-90 dose confirmation study to verify and confirm that the infectious endpoint has been reached. The infectious endpoint is positive nasopharyngeal culture(s) and/or polymerase chain reaction(s) (PCR(s)) for B. pertussis with concurrent or subsequent development of mild pertussis disease symptoms such as rhinorrhea and cough within the 16-day inpatient period following challenge. The trial is an open-label, phase 1, dose escalation, self-contained trial; participants will be allocated to challenge dose groups to receive a single intranasal dose of challenge inoculum. All participants will receive a 5-day course of azithromycin eradication therapy either 24-48 hours after they develop symptoms or at the end of the 16-day postchallenge observation period. The optimal/target inoculum is one that induces mild symptomatic infection and detection of B. pertussis in nasopharyngeal cultures in 70%-90% of participants receiving it, to establish a safe and reproducible pertussis CHIM. Safety monitoring includes close clinical observation during a 16-21-day inpatient postchallenge period in the Canadian Center for Vaccinology's Challenge Unit, a Data and Safety Monitoring Board, and participant Diary Cards.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pertussis
Keywords
Bordetella pertussis, Pertussis, Whooping cough, Controlled human infection model, Human challenge, Phase 1 clinical trial, Immune response

7. Study Design

Primary Purpose
Other
Study Phase
Phase 1
Interventional Study Model
Sequential Assignment
Model Description
Study 1 is a dose-escalation/de-escalation study in which participants will be allocated consecutively to a challenge dose group (arm) with predetermined dose level based on a decision algorithm. (All potential challenge dose groups are listed below, but not all groups may be required.)
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
66 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Study 1 (Dose-identification study), Dose 1
Arm Type
Experimental
Arm Description
Challenge dose of 10^3 cfu B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 2
Arm Type
Experimental
Arm Description
Challenge dose of 5 x 10^3 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 3
Arm Type
Experimental
Arm Description
Challenge dose of 10^4 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 4
Arm Type
Experimental
Arm Description
Challenge dose of 5 x 10^4 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 5
Arm Type
Experimental
Arm Description
Challenge dose of 10^5 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 6
Arm Type
Experimental
Arm Description
Challenge dose of 5 x 10^5 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 7
Arm Type
Experimental
Arm Description
Challenge dose of 10^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 8
Arm Type
Experimental
Arm Description
Challenge dose of 5 x 10^6 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 9
Arm Type
Experimental
Arm Description
Challenge dose of 10^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Arm Title
Study 1 (Dose-identification study), Dose 10
Arm Type
Experimental
Arm Description
Challenge dose of 5 x 10^7 CFU B. pertussis in 0.2 mL (0.1 mL per naris)
Intervention Type
Biological
Intervention Name(s)
Bordetella pertussis D420
Intervention Description
Intranasal inoculation of Bordetella pertussis D420 in each naris on Day 0 of the study.
Primary Outcome Measure Information:
Title
Number of participants with mild symptoms of early pertussis disease postchallenge
Description
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.
Time Frame
Day 0 (challenge day) to Day 16
Secondary Outcome Measure Information:
Title
Number of participants who demonstrate shedding of Bordetella pertussis postchallenge as determined by positive culture and/or PCR test of nasopharyngeal samples
Description
The presence of B. pertussis is detected by positive culture (i.e., presence of any B. pertussis colonies) of nasopharyngeal samples. It is also detected by a positive PCR (polymerase chain reaction) test of nasopharyngeal samples. Both methods are used in this study; a positive result in either culture and/or PCR test demonstrates shedding of B. pertussis.
Time Frame
Day 1 to Day 14

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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 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 Documented bilateral oophorectomy Documented and current bilateral tubal ligation or occlusion Currently fully vaccinated against SARS-CoV-2/COVID-19 according to provincial Public Health guidelines. If there is a reported history of SARS-CoV-2/COVID-19 infection, the participant must be asymptomatic for >4 weeks. 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. 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. 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). Known allergy to macrolides including azithromycin or erythromycin, history of Clostridium difficile within last 2 months. Any contraindication to receiving azithromycin. 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 or vaccine (including SARS-CoV-2/COVID-19 vaccine) within 6 months prior to challenge. An investigational vaccine is defined as a vaccine that is still being tested in clinical trials or one that has not yet been authorized for use in Canada for administration by public vaccine programs. Receipt of any authorized vaccines within 2 weeks of being challenged with B. pertussis in this study. (This is to avoid attributing any AEs from these vaccines to the B. pertussis challenge, which would skew the study results.) Current laboratory-confirmed SARS-CoV-2/COVID-19 infection. Previous moderate or severe laboratory-confirmed SARS-CoV-2/COVID-19 infection that required hospitalization. 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. Symptoms indicative of acute respiratory illness (such as fever, cough, difficulty breathing) identified during the physical examination done on Day -1 (check-in) or Day 0 before a participant is challenged. History of Bell's Palsy and/or facial paralysis. Receipt of facial cosmetic filler in the past 3 months.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kylie Peacock
Phone
902-470-8141
Email
kylie.peacock@iwk.nshealth.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Scott A. Halperin, MD
Organizational Affiliation
Dalhousie University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Canadian Center for Vaccinology
City
Halifax
State/Province
Nova Scotia
ZIP/Postal Code
B3K 6R8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kylie Peacock
Phone
902-470-8141
Email
kylie.peacock@iwk.nshealth.ca
First Name & Middle Initial & Last Name & Degree
Scott A. Halperin, MD
First Name & Middle Initial & Last Name & Degree
Joanne M. Langley, MD, MSc
First Name & Middle Initial & Last Name & Degree
Jeannette L. Comeau, MD
First Name & Middle Initial & Last Name & Degree
Shelly A. McNeil, MD
First Name & Middle Initial & Last Name & Degree
May ElSherif, MBBS, MSc

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.challengeunit.ca/
Description
Canadian Center for Vaccinology Challenge Unit home page
URL
http://centerforvaccinology.ca
Description
Canadian Center for Vaccinology home page

Learn more about this trial

Establishing a Controlled Human Infection Model of Bordetella Pertussis

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