Establishing a Controlled Human Infection Model of Pertactin-deficient Bordetella Pertussis
ConditionPertussis (Whooping Cough)
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18-50
SponsorDalhousie University
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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.
Disqualifiers
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).
Trial design
Design model
Sequential
Treatments tested in this trial
Biological: Bordetella pertussis J820
Biological/VaccineIntranasal inoculation of Bordetella pertussis J820 in each naris on Day 1 of the study.
Treatment groups
60 Participants
are divided into 5 treatment groupsGroup A: Group 1: Dose Number 5 (10^5)Experimental treatment 1 intervention
Group B: Group 2: Dose Number 7 (10^6)Experimental treatment 1 intervention
Group C: Group 3: Dose Number 9 (10^7)Experimental treatment 1 intervention
Group D: Group 4: Dose Number 11 (10^8)Experimental treatment 1 intervention
Group E: Group 5: Dose Number 13 (10^9)Experimental treatment 1 intervention
Trial outcomes
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).
Time frame
Study Day 1 up to Study Day 29Secondary outcomes
1
Secondary Outcome Measures
• To measure the rate of cough and describe the clinical presentation via: 1. Self-reporting 2. Clinical assessment
Time frame
Study Day 1 up to Study Day 292
Secondary Outcome Measures
• To evaluate the immune response following challenge associated with infection via: 1\. Humoral immune responses (analyte; unit; sample; technique): A) Anti-PT Antibodies; IU/mL; Serum; ELISA B) Anti-FHA Antibodies; IU/mL; Serum; ELISA C) Anti-PRN Antibodies; IU/mL; Serum; ELISA D) Anti-FIM Antibodies; EU/mL; Serum; ELISA
Time frame
Day 1 up to Study Day 1813
Secondary Outcome Measure
• To evaluate the immune response following challenge associated with infection via: 2\. Cellular \& Cellular-mediated immune responses Cellular: A) Eotaxin-2, Perfornin, Granzyme-A \& Granzyme-B; all pg/mL, by nasal wash using Luminex Cellular-mediated: A) Neutrophil CD16+, B cell CD19+, T Cell CD4+, T cells CD8+, Mucosal associated invariant T cell(MAIT) cells, NK cell CD3-CD56+, Monocyte CD14+, Eosinophil Siglec8+, gamma delta T cell; all % \& absolute count, by whole blood \& nasal swab using Flow cytometry
Time frame
Time Frame: Day 1 up to Study Day 1814
Secondary Outcome Measures
• To explore the time course of azithromycin therapy in clearing infection and/or symptoms, via testing during treatment as applicable via: 1\. B. pertussis laboratory testing of samples (culture, PCR): A) The mean number of days to culture negativity (i.e., bacterial count of zero in both NW and NPA samples) in days (with a 95% confidence interval) following treatment. B) The mean number of days to PCR negativity (i.e., PCR negative for each of the targets, that is IS481 and ptxS1 in both NW and NPA samples in days (with a 95% CI) following treatment. C) The cumulative proportion of participants that are negative by day following treatment by culture and PCR.
Time frame
Study Day 1 up to Study Day 29Other outcomes
1
Exploratory Outcome Measures
• To recommend optimal time points for the collection of biological specimens that facilitate studying mucosal and systemic immune responses to pertussis infection and/or vaccination will be measured via: 1\. Collective review of the results from all laboratory testing conducted to measure the previous outcomes.
Time frame
Study Day 1 up to Study Day 1812
Exploratory Outcome Measures
• Contributing samples from the study to the CDC biorepository will be measured via: 1\. Estimating the proportion of samples for which a portion will be submitted to the biorepository.
Time frame
Study Day 1 Up to Study Day 181Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Dalhousie University
Lead sponsor
Centers for Disease Control and Prevention
Collaborator
Source ClinicalTrials.gov