A Phase 2b, Placebo-Controlled, Randomized Study of BPZE1 Intranasal Pertussis Vaccine in Healthy Adults to Assess Protection Against Colonization Following Challenge With Virulent Wild-Type Bordetella Pertussis
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 53
- 试验地点
- 2
- 主要终点
- Number of Participants Colonized Following Virulent Challenge
研究概览
简要总结
This is a randomised, double-blinded, placebo-controlled trial of BPZE1 that includes virulent B. pertussis challenge followed by a safety follow-up.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Correctly answer all questions in the questionnaire provided during the consent process to ensure understanding of the study
- •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
- •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
- •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
- •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)
- •Willing to provide written agreement to and abide by infection control rules from challenge until 1 week following completion of azithromycin eradication
排除标准
- •Body mass index <17 or >30 kg/m2
- •History of being vaccinated against pertussis within 5 years of enrolment
- •History of never being vaccinated for pertussis in lifetime
- •A diagnosis of pertussis by laboratory confirmation or by physician diagnosis in the past 5 years
- •Previously participated in a pertussis challenge study
- •Screening laboratory values outside of the normal ranges
- •Existing chronic disorders of lung, kidney, heart, liver, diabetes, immunodeficiency, autoimmune or significant neurologic condition
- •Use of illicit drugs (excluding marijuana), evidenced by urine toxicology at Screening or a history of drug/alcohol abuse within the past 2 years
- •History of active cancer (malignancy) in the last 10 years (except for adequately treated non-melanomatous skin carcinoma)
- •History of Guillain-Barré syndrome (genetic/congenital or acquired)
- •History of head trauma with potential of cribriform plate fracture within 1 year prior to Day 0
- •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
- •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.
- •Received immunoglobulins or any blood products within 3 months prior to study vaccine administration or planned receipt during the study
- •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
- •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
- •Known hypersensitivity to any component of the study vaccine
- •Contraindications or allergic to azithromycin, erythromycin or other macrolide antibiotics
- •Taking medication that may interact with azithromycin (e.g., nelfinavir, warfarin, digoxin and phenytoin)
- •Inability to adhere to the protocol, visit schedule or sample collection needs (including housing in the challenge unit)
- •Participation in any other clinical trial for the testing of an unlicensed product during the previous 3 months or planned during the study conduct
研究组 & 干预措施
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.
干预措施: BPZE1 (Biological)
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.
干预措施: Azithromycin (Drug)
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.
干预措施: Bordetella Pertussis Challenge Strain (Other)
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.
干预措施: Placebo (Biological)
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.
干预措施: Azithromycin (Drug)
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.
干预措施: Bordetella Pertussis Challenge Strain (Other)
结局指标
主要结局
Number of Participants Colonized Following Virulent Challenge
时间窗: 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.
次要结局
- GMFR of Mucosal Anti-pertussis S-IgA Antibody(Day 28)
- GMFR of Serum IgA Antibody(Day 28)
- GMFR of Serum IgG Antibody(Day 28)
- Safety: Number of Participants With Solicited AEs for Reactogenicity(Day 7)
- Safety: Number of Participants With Treatment Emergent Adverse Events(Day 28)
- Safety: Number of Participants With TEAEs Related to Vaccination or Related to Challenge(Day 60-120 post vaccination and Day 90 post challenge)
- Safety: Number of Participants With AESI and SAE(Day 180)