Bordetella Pertussis, Whooping Cough, Pertussis/Whooping Cough
Conditions
Keywords
Bordetella Pertussis, BPZE1, Vaccine, Live Attenuated Vaccine, Challenge Study
Brief summary
This is a randomised, double-blinded, placebo-controlled trial of BPZE1 that includes virulent B. pertussis challenge followed by a safety follow-up.
Detailed description
This Phase 2b challenge study will investigate colonisation rates, immunologic response, and the safety of BPZE1 vaccination to potentially protect against colonising, virulent wild-type B. pertussis infection in healthy adults using a virulent challenge model. Consenting, eligible participants will receive a single dose of BPZE1 or placebo. 2-4 months later they will be challenged with B. pertussis and admitted to a challenge unit. Participants will remain in the challenge unit for a total of 17 days and 16 nights during which time they will be monitored closely. If a participant develops symptoms of pertussis (per investigator discretion), antibiotic (azithromycin) will be started and the participant will remain in the unit for 3 additional days of observation before discharge. If symptoms of pertussis do not develop, then participants will receive antibiotic (azithromycin) from Days 14-16 of the challenge unit stay. Participants will undergo safety follow-up for at least 6 months post-vaccination and at least 3 months post-challenge, for a total follow-up of 6-7 months.
Interventions
BIOLOGICALBPZE1
Live attenuated vaccine
BIOLOGICALPlacebo
Placebo
DRUGAzithromycin
Antibiotic
OTHERBordetella Pertussis Challenge Strain
Challenge Strain
Sponsors
ILiAD Biotechnologies
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 50 Years
Healthy volunteers
Yes
Inclusion criteria
Key Inclusion Criteria: 1. Correctly answer all questions in the questionnaire provided during the consent process to ensure understanding of the study 2. Willing to refrain from any nasal sprays (including intranasal steroid sprays) and nasal washes not part of the study for 14 days prior to vaccination (Day 0) and for 28 days following vaccination and challenge 3. Non-smoker at the time of enrolment, has not smoked (or vaped) in the past 7 days prior to vaccination (including marijuana), and is willing not to smoke (or vape; including marijuana) from the time of vaccination throughout the challenge unit phase 4. Sufficiently vaccinated (per site and local guidelines) against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; proof of vaccination required) \>14 days prior to study vaccination 5. Able to understand and comply with planned study procedures including admission for virulent challenge for 17 days and willingness to take the curative antibiotic regimen (azithromycin after inoculation with B. pertussis) 6. Willing to provide written agreement to and abide by infection control rules from challenge until 1 week following completion of azithromycin eradication
Exclusion criteria
1. Body mass index \<17 or \>30 kg/m2 2. History of being vaccinated against pertussis within 5 years of enrolment 3. History of never being vaccinated for pertussis in lifetime 4. A diagnosis of pertussis by laboratory confirmation or by physician diagnosis in the past 5 years 5. Previously participated in a pertussis challenge study 6. Screening laboratory values outside of the normal ranges 7. Existing chronic disorders of lung, kidney, heart, liver, diabetes, immunodeficiency, autoimmune or significant neurologic condition 8. Use of illicit drugs (excluding marijuana), evidenced by urine toxicology at Screening or a history of drug/alcohol abuse within the past 2 years 9. History of active cancer (malignancy) in the last 10 years (except for adequately treated non-melanomatous skin carcinoma) 10. History of Guillain-Barré syndrome (genetic/congenital or acquired) 11. History of head trauma with potential of cribriform plate fracture within 1 year prior to Day 0 12. History of nasal or sinus surgery within 6 months or receipt of facial cosmetic fillers within 3 months prior to Day 0 or diagnosis of nasal polyps 13. Received immunosuppressive therapy or other immune-modifying drugs (including but not limited to systemic corticosteroids, biologics and methotrexate) in the past 6 months, is on scheduled immunosuppressive therapy or is planning to start immunosuppressive therapy during the trial. 14. Received immunoglobulins or any blood products within 3 months prior to study vaccine administration or planned receipt during the study 15. Lives in the same home or has routine contact (face to face \<2 meters) with persons with known immunodeficiency including persons on immunosuppressant therapy, from study vaccination to challenge and for 1 week after exiting the challenge unit 16. Resides in the same home, works regularly with, or has contact (face to face \<2 meters), with infants less than 1 year of age, partially immunised infants or pregnant women, adults \>65 years of age who have not received a dose of acellular pertussis vaccine (e.g. Tdap) within the past 10 years from study vaccination to challenge and for 1 week after exiting the challenge unit 17. Known hypersensitivity to any component of the study vaccine 18. Contraindications or allergic to azithromycin, erythromycin or other macrolide antibiotics 19. Taking medication that may interact with azithromycin (e.g., nelfinavir, warfarin, digoxin and phenytoin) 20. Inability to adhere to the protocol, visit schedule or sample collection needs (including housing in the challenge unit) 21. Participation in any other clinical trial for the testing of an unlicensed product during the previous 3 months or planned during the study conduct
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Colonized Following Virulent Challenge | Challenge Day 9, 11 or 14 | Participants by treatment group (BPZE1 and placebo) colonized on any day (Challenge Day 9, 11 or 14) following virulent challenge as determined by culture. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| GMFR of Serum IgA Antibody | Day 28 | The GMFR of serum IgA antibody (WCE, FHA, PRN, PT and FIM2/3) from baseline to Day 28 (BPZE1 and placebo) |
| GMFR of Serum IgG Antibody | Day 28 | The GMFR of serum IgG antibody (WCE, FHA, PRN, PT and FIM2/3) from baseline to Day 28 (BPZE1 and placebo) |
| Safety: Number of Participants With Solicited AEs for Reactogenicity | Day 7 | Occurrence and intensity of solicited AEs for nasal/respiratory and systemic reactogenicity through 7 days following vaccination by treatment group (BPZE1 and placebo) |
| GMFR of Mucosal Anti-pertussis S-IgA Antibody | Day 28 | The geometric mean fold rise (GMFR) of mucosal anti-pertussis S-IgA antibody (whole cell extract \[WCE\], FHA, PRN, PT and fimbriae types 2 and 3 \[FIM2/3\]) from baseline to Day 28 (BPZE1 and placebo). Secretory IgA to be normalized (\[specific S-IgA\]/\[total S-IgA\]) |
| Safety: Number of Participants With TEAEs Related to Vaccination or Related to Challenge | Day 60-120 post vaccination and Day 90 post challenge | Occurrence and intensity of TEAEs related to vaccination from time of vaccination to challenge or related to challenge for 3 months after challenge by treatment group (BPZE1 and placebo) |
| Safety: Number of Participants With AESI and SAE | Day 180 | Occurrence, intensity, and relationship to study vaccine of AESIs and SAEs from vaccination through end of study (EOS) by treatment group (BPZE1 and placebo) |
| Safety: Number of Participants With Treatment Emergent Adverse Events | Day 28 | Occurrence and intensity of TEAEs through 28 days following study vaccination and following challenge by treatment group (BPZE1 and placebo) |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BPZE1 Participants will receive an intranasal dose of BPZE1 via the mucosal atomization device followed by a dose of the challenge strain (B. pertussis strain 1917) approximately 60-120 days later. Participants will receive azithromycin for 3 days beginning 14 days after administration of the challenge strain.
BPZE1: Live attenuated B. pertussis vaccine
Azithromycin: Antibiotic
Bordetella Pertussis strain 1917 Challenge: Challenge Strain | 26 |
| Placebo Participants will receive an intranasal dose of placebo via the mucosal atomization device followed by a dose of the challenge strain (B. pertussis strain 1917) approximately 60-120 days later. Participants will receive azithromycin for 3 days beginning 14 days after administration of the challenge strain.
Placebo: Placebo
Azithromycin: Antibiotic
Bordetella Pertussis strain 1917 Challenge: Challenge Strain | 27 |
| Total | 53 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 0 | 2 |
Baseline characteristics
| Characteristic | Placebo | Total | BPZE1 |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants | 53 Participants | 26 Participants |
| Age, Continuous | 31.4 years STANDARD_DEVIATION 9.16 | 30.4 years STANDARD_DEVIATION 8.49 | 29.3 years STANDARD_DEVIATION 7.77 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants | 5 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 6 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 42 Participants | 22 Participants |
| Region of Enrollment United Kingdom | 27 participants | 53 participants | 26 participants |
| Sex: Female, Male Female | 13 Participants | 27 Participants | 14 Participants |
| Sex: Female, Male Male | 14 Participants | 26 Participants | 12 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 27 |
| other Total, other adverse events | 7 / 26 | 9 / 27 |
| serious Total, serious adverse events | 0 / 26 | 0 / 27 |
Outcome results
Primary
Number of Participants Colonized Following Virulent Challenge
Participants by treatment group (BPZE1 and placebo) colonized on any day (Challenge Day 9, 11 or 14) following virulent challenge as determined by culture.
Time frame: Challenge Day 9, 11 or 14
Population: Subjects who received an adequate inoculum defined prospectively as challenge dose \>=0.5x10\^5 CFU were evaluated.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BPZE1 | Number of Participants Colonized Following Virulent Challenge | 8 Participants |
| Placebo | Number of Participants Colonized Following Virulent Challenge | 12 Participants |
Secondary
GMFR of Mucosal Anti-pertussis S-IgA Antibody
The geometric mean fold rise (GMFR) of mucosal anti-pertussis S-IgA antibody (whole cell extract \[WCE\], FHA, PRN, PT and fimbriae types 2 and 3 \[FIM2/3\]) from baseline to Day 28 (BPZE1 and placebo). Secretory IgA to be normalized (\[specific S-IgA\]/\[total S-IgA\])
Time frame: Day 28
Population: Available baseline and Day 28 samples
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 | GMFR of Mucosal Anti-pertussis S-IgA Antibody | FHA | 5.0 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Mucosal Anti-pertussis S-IgA Antibody | PT | 1.7 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Mucosal Anti-pertussis S-IgA Antibody | PRN | 5.3 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Mucosal Anti-pertussis S-IgA Antibody | FIM 2/3 | 9.1 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Mucosal Anti-pertussis S-IgA Antibody | WCE | 3.2 Geometric Mean Fold Rise |
| Placebo | GMFR of Mucosal Anti-pertussis S-IgA Antibody | FIM 2/3 | 1.1 Geometric Mean Fold Rise |
| Placebo | GMFR of Mucosal Anti-pertussis S-IgA Antibody | WCE | 1.0 Geometric Mean Fold Rise |
| Placebo | GMFR of Mucosal Anti-pertussis S-IgA Antibody | FHA | 1.1 Geometric Mean Fold Rise |
| Placebo | GMFR of Mucosal Anti-pertussis S-IgA Antibody | PRN | 1.0 Geometric Mean Fold Rise |
| Placebo | GMFR of Mucosal Anti-pertussis S-IgA Antibody | PT | 1.2 Geometric Mean Fold Rise |
Secondary
GMFR of Serum IgA Antibody
The GMFR of serum IgA antibody (WCE, FHA, PRN, PT and FIM2/3) from baseline to Day 28 (BPZE1 and placebo)
Time frame: Day 28
Population: Available baseline and Day 28 samples
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 | GMFR of Serum IgA Antibody | FHA | 3.0 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgA Antibody | PT | 1.5 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgA Antibody | PRN | 3.7 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgA Antibody | FIM 2/3 | 5.0 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgA Antibody | WCE | 2.6 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgA Antibody | FIM 2/3 | 1.0 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgA Antibody | WCE | 1.2 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgA Antibody | FHA | 1.1 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgA Antibody | PRN | 1.0 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgA Antibody | PT | 1.1 Geometric Mean Fold Rise |
Secondary
GMFR of Serum IgG Antibody
The GMFR of serum IgG antibody (WCE, FHA, PRN, PT and FIM2/3) from baseline to Day 28 (BPZE1 and placebo)
Time frame: Day 28
Population: Available baseline and Day 28 samples
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) |
|---|---|---|---|
| BPZE1 | GMFR of Serum IgG Antibody | FHA | 1.7 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgG Antibody | PT | 2.1 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgG Antibody | PRN | 3.1 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgG Antibody | FIM 2/3 | 2.9 Geometric Mean Fold Rise |
| BPZE1 | GMFR of Serum IgG Antibody | WCE | 1.5 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgG Antibody | FIM 2/3 | 0.9 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgG Antibody | WCE | 1.1 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgG Antibody | FHA | 1.0 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgG Antibody | PRN | 1.1 Geometric Mean Fold Rise |
| Placebo | GMFR of Serum IgG Antibody | PT | 1.0 Geometric Mean Fold Rise |
Secondary
Safety: Number of Participants With AESI and SAE
Occurrence, intensity, and relationship to study vaccine of AESIs and SAEs from vaccination through end of study (EOS) by treatment group (BPZE1 and placebo)
Time frame: Day 180
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BPZE1 | Safety: Number of Participants With AESI and SAE | AESI (COVID-19) | 0 Participants |
| BPZE1 | Safety: Number of Participants With AESI and SAE | SAE | 0 Participants |
| Placebo | Safety: Number of Participants With AESI and SAE | AESI (COVID-19) | 1 Participants |
| Placebo | Safety: Number of Participants With AESI and SAE | SAE | 0 Participants |
Secondary
Safety: Number of Participants With Solicited AEs for Reactogenicity
Occurrence and intensity of solicited AEs for nasal/respiratory and systemic reactogenicity through 7 days following vaccination by treatment group (BPZE1 and placebo)
Time frame: Day 7
Population: Safety analysis set
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BPZE1 | Safety: Number of Participants With Solicited AEs for Reactogenicity | Systemic | 18 Participants |
| BPZE1 | Safety: Number of Participants With Solicited AEs for Reactogenicity | Nasal/Respiratory | 17 Participants |
| Placebo | Safety: Number of Participants With Solicited AEs for Reactogenicity | Nasal/Respiratory | 20 Participants |
| Placebo | Safety: Number of Participants With Solicited AEs for Reactogenicity | Systemic | 16 Participants |
Secondary
Safety: Number of Participants With TEAEs Related to Vaccination or Related to Challenge
Occurrence and intensity of TEAEs related to vaccination from time of vaccination to challenge or related to challenge for 3 months after challenge by treatment group (BPZE1 and placebo)
Time frame: Day 60-120 post vaccination and Day 90 post challenge
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BPZE1 | Safety: Number of Participants With TEAEs Related to Vaccination or Related to Challenge | 4 Participants |
| Placebo | Safety: Number of Participants With TEAEs Related to Vaccination or Related to Challenge | 8 Participants |
Secondary
Safety: Number of Participants With Treatment Emergent Adverse Events
Occurrence and intensity of TEAEs through 28 days following study vaccination and following challenge by treatment group (BPZE1 and placebo)
Time frame: Day 28
Population: Safety analysis set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BPZE1 | Safety: Number of Participants With Treatment Emergent Adverse Events | 7 Participants |
| Placebo | Safety: Number of Participants With Treatment Emergent Adverse Events | 9 Participants |