Phase 2b Study of BPZE1 Intranasal Pertussis Vaccine in Adults to Assess Immunological Response and Safety Profile of 1-Dose (Prime) and 2-Doses (Prime+Boost) Schedule, Compared to a Boostrix™ Prime Dose With or Without a BPZE1 Boost Dose
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 300
- 试验地点
- 6
- 主要终点
- Safety - Number of Participants With Nasal/Respiratory Solicited Adverse Events (AEs)
研究概览
简要总结
This study evaluates the safety and immunogenicity of the BPZE1 live attenuated pertussis vaccine, intended to prevent nasopharyngeal colonization and pertussis disease, and compares a single (prime) BPZE1 dose or BPZE1 2-dose (prime + boost) to a single (prime) Boostrix or Boostrix prime + BPZE1 boost.
详细描述
This study evaluates the safety and immunogenicity of the BPZE1 live attenuated pertussis vaccine, intended to prevent nasopharyngeal colonization and pertussis disease, and compares a single (prime) BPZE1 dose or BPZE1 2-dose (prime + boost) to a single (prime) Boostrix or Boostrix prime + BPZE1 boost. This is a multi-center, randomized, placebo-controlled, and observer blinded trial in healthy adults with a 6 month safety follow-up after the last vaccination.
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
- •Is a male or nonpregnant female 18 to 50 years of age, inclusive, on Day 1 (primary vaccination).
- •Is capable of understanding the written informed consent, provides signed and witnessed written informed consent, and agrees to comply with protocol requirements.
- •Female subjects must be nonpregnant and nonlactating and meet 1 of the following criteria:
- •Postmenopausal (defined as 12 consecutive months with no menses without an alternative medical cause or documented plasma follicle-stimulating hormone level in the postmenopausal range);
- •Surgically sterile (ie, hysterectomy, bilateral tubal ligation, or bilateral oophorectomy).
- •NOTE: These procedures and laboratory test results must be confirmed by physical examination, or by subject recall of specific date and hospital/facility of procedure, or by medical documentation of said procedure.
- •Is of childbearing potential (defined as any female who has experienced menarche and who is NOT permanently sterile or postmenopausal), agrees to be heterosexually inactive from at least 21 days prior to enrollment and through 3 months after the boosting vaccination or agrees to consistently use any of the following methods of contraception from at least 21 days prior to enrollment and through 3 months after the boosting vaccination:
- •i. Condoms (male or female) with spermicide ii. Diaphragm with spermicide iii. Cervical cap with spermicide iv. Intrauterine device v. Oral or patch contraceptives vi. Norplant®, Depo-Provera®, or other FDA approved contraceptive method that is designed to protect against pregnancy.
- •NOTE: Periodic abstinence (eg, calendar, ovulation, symptothermal, post ovulation methods) and withdrawal are not acceptable methods of contraception.
- •Has a stable health status as assessed by the investigator, as established by physical examination, vital sign measurements, and medical history.
- •Has access to a consistent and reliable means of telephone contact, which may be in the home, workplace, or by personal mobile electronic device.
- •Is able to understand and comply with planned study procedures.
- •Lives a reasonable distance from the clinical site to be able to travel to and from the clinical site for follow-up visits and agrees to go to the clinical site for evaluation (or provide medical record access if evaluated elsewhere) in the event of an AE.
- •Agrees to stay in contact with the clinical site for the duration of the study, has no current plans to move from the study area, and provides updated contact information as necessary.
排除标准
- •History of being vaccinated in the past 5 years against pertussis.
- •Any significant past reaction to any component of Boostrix (at the discretion of the investigator).
- •Subject reported diagnosis of pertussis in the past 10 years (must be laboratory confirmed or physician diagnosed from medical records).
- •Vital signs by FDA toxicity scoring >1 (may be repeated once during the screening period to allow for inclusion and the most recent measurement taken at baseline).
- •Chronic illness being treated actively and with evidence of recent intervention for worsening or fluctuating symptoms (at the discretion of the investigator).
- •The subject has a history of active cancer (malignancy) in the last 10 years (exception is subjects with adequately treated non melanomatous skin carcinoma, who may participate in the study).
- •Current use of any smoking products and unwillingness to refrain from the use of any smoking products from screening through 28 days after the boosting vaccination.
- •Use of narcotic drugs, evidenced by urine toxicology screen or a history of drug/alcohol abuse within the past 2 years.
- •Has donated blood or suffered from blood loss of more than 450 mL (1 unit of blood) within 60 days prior to screening or donated plasma within 14 days prior to screening.
- •Receipt of immunoglobulin, blood-derived products, systemic corticosteroids, or other immunosuppressant drugs within 90 days prior to Day
- •Asthma, obstructive nasal canal, recurrent or acute sinusitis or other chronic respiratory problems inclusive of the diagnosis of any significant pulmonary disease.
- •History of nasal surgery or Bell's palsy.
- •Use of repeated nasal sprays, Neti pot, routine nasal washing within the past 1 month (more than 2 times per week). Subjects must agree to refrain from use of any of these modalities through Day
- •A temporary exclusion to vaccinate if acute respiratory tract infection or rhinorrhea or temperature >100.4°F (no symptoms for 3 days prior to vaccination day). Subjects may be vaccinated if they stay within the vaccination window (screening [30 days] or at the time of the booster [10 days]).
- •NOTE: If a subject exceeds the screening window, they must be reconsented and screening must be reinitiated.
- •Use of corticosteroids in the respiratory tract (eg, nasal steroids, inhaled steroids) within 30 days prior to Day
- •Receipt of a licensed vaccine within the last 30 days prior to Day 1 or planned vaccination during the active study conduct through Day
- •In the case of seasonal influenza, vaccination should not be withheld and is not contraindicated for subject participation. However, vaccination should be planned outside of a 30 day pre- and 30 day post vaccination window whenever possible.
- •Known hypersensitivity to any component of the study vaccines.
- •Participation in any other clinical trial for the testing of an unlicensed product during the previous 6 months or planned during the study conduct.
- •Inability to adhere to the protocol, including plans to move from the area.
- •Personal history or family (first degree) history of congenital or hereditary immunodeficiency.
- •Past or present infection with human immunodeficiency virus, hepatitis B, or hepatitis C by screening test.
- •Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic).
- •Any neurological disease or history of significant neurological disorder (eg, meningitis, seizures, multiple sclerosis, vasculitis, migraines, Guillain-Barré syndrome [genetic/congenital or acquired]).
- •Any medical condition that, in the opinion of the investigator, might interfere with the evaluation of the study objectives or might affect the safety of the individual, (eg, major depression or history of suicidal attempt).
- •Toxicity grading >1 for screening laboratory test results for kidney, hepatic, and hematologic values (may be repeated once during the screening period to allow for inclusion and the most recent measurement taken at baseline). See Table 13 2 for specifically designated parameters.
- •Body mass index <17 kg/m2 or >40 kg/m
- •Frequent contact with children less than 1 year of age (parent, childcare worker, nurse, etc.) or residence in the same household as persons with known immunodeficiency including persons on immunosuppressant therapy.
- •Study team member or first-degree relative of study team member.
结局指标
主要结局
Safety - Number of Participants With Nasal/Respiratory Solicited Adverse Events (AEs)
时间窗: Through 7 Days Following Day 1 Vaccination
Number of participants with Solicited AEs (nasal/respiratory reactogenicity events) by Grade - Any Day Grade 1 through 3 and Grade 3. Grading of reactogenicity is defined per protocol as Grade 1 (mild), Grade 2 (moderate), and Grade 3 (severe) AEs.
Safety Lead-in Participants With Abnormal Laboratory Parameters (BPZE1 10^7 Safety Lead-In)
时间窗: Days 8 and 92
Number of participants in the safety lead-in cohort with Grade 2 through 4 laboratory abnormalities: Serum Chemistry - Bilirubin, Creatinine, ALT, AST; WBC, Hemoglobin, Prothrombin time, Partial Thromboplastin Time. Grading of laboratory results is defined per protocol as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe) and Grade 4 (potentially life-threatening) laboratory abnormalities (DHHS 2007).
Safety - Number of Participants With Systemic Solicited AEs
时间窗: Through 7 Days Following Day 1 Vaccination
Number of participants with Solicited AEs (systemic reactogenicity events) by Grade - Any Day Grade 1 through 3 and Grade 3. Grading of reactogenicity is defined per protocol as Grade 1 (mild), Grade 2 (moderate), and Grade 3 (severe) AEs.
Number of Participants With Nasal Mucosal Seroconversion (Immunoglobulin A [IgA])
时间窗: Days 29 and 113
Number of participants who achieve mucosal seroconversion (IgA) against at least 1 anti-pertussis antibody for whole cell extract (WCE), pertussis toxin (PT), filamentous hemagglutinin (FHA), or pertactin (PRN) on Day 29 or Day 113. Mucosal seroconversion was defined as a 2-fold increase over the baseline value or a 4-fold increase over the minimal detection limit of the assay (whenever the baseline value was below the detection limits of the assay).
Safety - Number of Participants With Local Solicited AEs
时间窗: Through 7 Days Following Day 1 Vaccination
Number of participants with Solicited AEs (local reactogenicity events) by Grade - Any Day Grade 1 through 4 and Grade 3 and 4. Grading of reactogenicity is defined per protocol as Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (potentially life-threatening) AEs.
次要结局
- Mucosal Immunogenicity - Summary of GMFRs of Mucosal Absolute S-IgA/Total S-IgA Against Whole Cell Extract by Vaccine Group and Time Point(Days 113, 169, 254)
- Safety - Number of Participants With Serious AEs(Days 114 to 254 (end of study))
- Safety - Number of Participants With Unsolicited AEs(Days 85 through 113)
- Systemic Immunogenicity - Summary of Systemic IgG Seroconversion Endpoints(9 months)
- Systemic Immunogenicity - Summary of GMFRs of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point(Days 113, 169 and 254)
- Colonization - Summary of Colonization for B. Pertussis Bacterial Culture From Nasal Sample by Timepoint(Days 92, 96, 113)
- Systemic Immunogenicity - Summary of Systemic IgA Seroconversion Endpoints(9 Months)
- Systemic Immunogenicity - Summary of Geometric Mean Fold Rises (GMFRs) of Systemic IgG Against Whole Cell Extract by Vaccine Group and Time Point(Days 29 and 85)
- Mucosal Immunogenicity - Summary of Mucosal Absolute S-IgA/Total S-IgA Seroconversion Endpoints(9 months)