Bordetella Pertussis Infection Model for Whooping Cough

Overseen By Kylie Peacock

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: Dalhousie University

Must not be taking: Antibiotics, Terfenadine, Astemizole, others

Disqualifiers: Chronic conditions, Cardiac/pulmonary disease, Psychiatric illness, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 5 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on understanding whooping cough, caused by the bacteria Bordetella pertussis, by testing different doses of the bacteria in healthy adults. The goal is to find a dose that safely causes a mild infection, aiding future vaccine and treatment development. Participants should be in good health and free of ongoing medical conditions requiring regular doctor visits. This trial targets individuals fully vaccinated against COVID-19 who have not had whooping cough recently or been vaccinated for it in the last five years. As a Phase 1 trial, the research aims to understand how the treatment works in people, offering participants a chance to contribute to groundbreaking medical research.

Do I have to stop taking my current medications to join the trial?

The trial requires that you stop taking certain medications, such as antibiotics and specific drugs like terfenadine, astemizole, theophylline, or cimetidine. If you're currently on these medications, you may need to stop them before participating.

What prior data suggests that this infection model is safe for humans?

Research shows that Bordetella pertussis, the bacterium causing whooping cough, produces toxins and leads to infection. In a previous study, researchers identified a safe and effective dose of this bacterium for controlled infection models. These studies aim to find a dose that causes only mild symptoms in healthy adults, allowing scientists to study the disease and immune response without severe illness.

In this trial, different doses of the Bordetella pertussis D420 strain are tested to find the safest option that still results in a mild infection. Although Bordetella pertussis can naturally cause serious illness, these controlled doses are carefully selected for safety. The trial is in its early stages, with researchers primarily focused on determining the safest amount to use.

Despite being an early-stage trial, the focus on finding the right dose underscores a strong emphasis on safety. This trial builds on other research efforts that have successfully identified safe doses in similar studies. This careful approach helps ensure that participants face minimal risk while contributing to important scientific knowledge about whooping cough. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for whooping cough involve antibiotics like azithromycin or erythromycin, which target the bacteria causing the infection. But the Bordetella pertussis D420 treatment takes a unique approach by acting as a challenge model to better understand the infection process. Researchers are excited about this because it provides a controlled way to study how the bacteria behave in the body, which can lead to the development of more effective vaccines or treatments. This innovative method could transform how we approach preventing and treating whooping cough in the future.

What evidence suggests that this trial's treatments could be effective for whooping cough?

Studies have shown that the pertussis strain D420 can cause mild cold-like symptoms in a controlled environment. This trial uses different doses of this strain to determine the right amount needed to safely produce these symptoms. Research indicates that while current vaccines protect against severe whooping cough, they don't completely stop the spread of Bordetella pertussis, the bacteria responsible for it. The trial aims to find a dose that causes mild symptoms in most participants. Early results from the various treatment arms suggest that different doses can achieve this, helping researchers learn how to better control whooping cough. ^{6 7 8 9 10}

Who Is on the Research Team?

Scott A. Halperin, MD

Principal Investigator

Dalhousie University

Are You a Good Fit for This Trial?

Healthy adults aged 18-40 who can follow the study's protocol. Women must use contraception and have a negative pregnancy test before the challenge. Excluded are pregnant or breastfeeding women, those with recent nasal surgery or respiratory infections, certain medication users, people living with young children or immunocompromised individuals, smokers/vapers, and anyone with a history of pertussis infection or vaccination against it within the last five years.

Inclusion Criteria

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

I am a premenopausal woman with certain surgical procedures done or fully vaccinated against COVID-19.

Good general health status, as determined by history and physical examination conducted no longer than 30 days prior to the challenge

Exclusion Criteria

My immune system is weakened due to a condition or medication.

I have smoked or vaped almost every day in the past 2 years.

Your heart's electrical activity is abnormal on an EKG.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Challenge and Observation

Participants receive a single intranasal dose of challenge inoculum and are observed for mild symptomatic infection and colonization

16-21 days

Inpatient stay

Treatment

Participants receive a 5-day course of azithromycin eradication therapy either 24-48 hours after symptom development or at the end of the observation period

5 days

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bordetella pertussis D420

Trial Overview The trial is testing Bordetella pertussis D420 to establish a safe dose that causes mild symptoms in healthy adults without causing serious illness. Participants will be monitored for colonization and symptomatic infection after receiving this bacterial challenge.

How Is the Trial Designed?

Group I: Sub-Study (Dose confirmation study), Cohort 11, Dose #11 Experimental Treatment 1 Intervention

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

Group II: Study 2 (Dose confirmation study), Cohort 9, Dose #9 Experimental Treatment 1 Intervention

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

Group III: Study 2 (Dose confirmation study), Cohort 9, Dose #10 Experimental Treatment 1 Intervention

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

Group IV: Study 2 (Dose confirmation study), Cohort 8, Dose #9 Experimental Treatment 1 Intervention

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

Group V: Study 2 (Dose confirmation study), Cohort 8, Dose #10 Experimental Treatment 1 Intervention

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

Group VI: Study 2 (Dose confirmation study), Cohort 11, Dose #10 Experimental Treatment 1 Intervention

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

Group VII: Study 2 (Dose confirmation study), Cohort 10, Dose #8 Experimental Treatment 1 Intervention

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

Group VIII: Study 1 (Dose-identification study), Cohort 7, Dose #9 Repeat Experimental Treatment 1 Intervention

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

Group IX: Study 1 (Dose-identification study), Cohort 6, Dose #9 Experimental Treatment 1 Intervention

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

Group X: Study 1 (Dose-identification study), Cohort 5, Dose #8 Experimental Treatment 1 Intervention

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

Group XI: Study 1 (Dose-identification study), Cohort 4, Dose #7 Experimental Treatment 1 Intervention

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

Group XII: Study 1 (Dose-identification study), Cohort 3, Dose #6 Experimental Treatment 1 Intervention

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

Group XIII: Study 1 (Dose-identification study), Cohort 2, Dose #5 Experimental Treatment 1 Intervention

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

Group XIV: Study 1 (Dose-identification study), Cohort 1, Dose #3 Experimental Treatment 1 Intervention

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

Who Is Running the Clinical Trial?

Dalhousie University

Lead Sponsor

Trials

177

Recruited

402,000+

Intravacc

Industry Sponsor

Trials

1

Recruited

80+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Centers for Disease Control and Prevention

Collaborator

Trials

902

Recruited

25,020,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12188742/

Highlights of the 14th International Bordetella Symposium - PMC Representatives from eight global regions shared data, unanimously reporting that pertussis rates were remarkably low during the pandemic.

2. cdc.gov cdc.gov/pertussis/php/surveillance/index.html

Pertussis Surveillance and Trends | Whooping Cough View pertussis data, including case counts and incidence by state and age, DTaP vaccination history of cases, and pertussis-related deaths.

3. pnas.org pnas.org/doi/10.1073/pnas.1314688110

Acellular pertussis vaccines protect against disease but fail ... In this study, we show nonhuman primates vaccinated with aP were protected from severe symptoms but not infection and readily transmitted Bordetella pertussis ...

4. fda.gov fda.gov/media/181937/download

Vaccines and Related Biological Products Advisory ... pertussis strain D420, with the goal of identifying a dose that elicits mild catarrhal symptoms in 70–90% of participants. Half-log doses above ...

5. nature.com nature.com/articles/s41541-024-00990-1

A novel outer membrane vesicle adjuvant improves ... While the aP vaccine is highly effective at preventing disease in vaccinated individuals, B. pertussis continues to circulate in humans leaving ...

6. canada.ca canada.ca/en/public-health/services/laboratory-biosafety-biosecurity/pathogen-safety-data-sheets-risk-assessment/bordetella-pertussis.html

Bordetella pertussis - Pathogen Safety Data Sheets B. pertussis is a strictly aerobic bacterium that produces various virulence factors and toxins that contribute to its pathogenicity.

7. academic.oup.com academic.oup.com/jid/article/229/2/376/7241294

Repeated Bordetella pertussis Infections Are Required to ... Our results indicate that it is possible to retrain aP-primed immune responses, but it will likely require an optimal booster and multiple doses.

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3501154/

Airborne Transmission of Bordetella pertussis - PMC Our results showed that 100% of exposed naive animals became infected even when physical contact was prevented, demonstrating that pertussis transmission occurs ...

9. fda.gov fda.gov/media/182039/download

The First North American Pertussis Controlled Human ... Infection Model (CHIM) by determining and confirming the optimal and safe Bordetella pertussis dose administered intranasally to healthy ...

10. cdc.gov cdc.gov/pertussis/hcp/clinical-overview/index.html

Clinical Overview of Pertussis | Whooping Cough Some observational studies suggest that pertussis infection can provide immunity for 4 to 20 years, but that it's not lifelong. An image of ...