A Phase 2A Partially-Blind Placebo Controlled Trial to Evaluate the Safety and Immunogenicity of Live Attenuated, Intranasal B. Pertussis Vaccine (BPZE1) in Healthy Adults
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Number of Participants Experiencing Solicited Systemic Reactogenicity AEs
研究概览
简要总结
This is a randomized, partially blind, placebo controlled, clinical trial evaluating a single intranasal dose of BPZE1 in healthy adults. The study will evaluate a lyophilized formulation of the product, with the goal of testing for the optimal dose for subsequent clinical trials. Fifty healthy adults, 18-49 years of age will be randomized to one of the four following treatment groups in a 3:3:3:1 ratio: 10^7 colony forming units (CFU) of BPZE1 administered by VaxINator device, 10^9 CFU of BPZE1 administered by VaxINator device, placebo administered by VaxINator device, 10^9 CFU of BPZE1 administered by needleless tuberculin syringe. Study duration will be approximately 12 months with a subject participation duration of approximately 6 months. The primary objective of this study is to assess the safety and tolerability of a single intranasal dose of either 10^7 or 10^9 CFU of lyophilized BPZE1 vaccine.
详细描述
This is a phase 2a, single center, randomized, partially blind, placebo controlled, clinical trial evaluating a single intranasal dose of either 10^7 colony forming units (CFU) or 10^9 CFU of BPZE1 in healthy adults. The study will evaluate a lyophilized formulation of the product, with the goal of testing for the optimal dose for subsequent clinical trials. Fifty healthy adults, 18-49 years of age will be randomized to one of the four following treatment groups in a 3:3:3:1 ratio: 10^7 CFU of BPZE1 administered by VaxINator device, 10^9 CFU of BPZE1 administered by VaxINator device, placebo administered by VaxINator device, 10^9 CFU of BPZE1 administered by needleless tuberculin syringe. Study duration will be approximately 12 months with a subject participation duration of approximately 6 months. The primary objective of this study is to assess the safety and tolerability of a single intranasal dose of either 10^7 or 10^9 CFU of lyophilized BPZE1 vaccine. The secondary objectives of this study are: 1) to assess the humoral immunogenicity of lyophilized BPZE1 vaccine at Day 15, Day 29 and Day 181 following receipt of one intranasal dose of 10^7 or 10^9 CFU of BPZE1; 2) to assess mucosal immunogenicity of lyophilized BPZE1 vaccine at Day 29 and Day 181 following receipt of one intranasal dose of 10^7 or 10^9 CFU of BPZE1; 3) to evaluate nasal clearance of BPZE1 by culture at Day 29 (and if still positive, at Day 46) following receipt of one intranasal dose of lyophilized BPZE1 vaccine of 10^7 or 10^9 CFU of BPZE1.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 49 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subjects eligible to participate in this study must meet all inclusion criteria:
- •Provide written informed consent prior to initiation of any study procedures.
- •Able to understand and comply with planned study procedures and be available for all study visits.
- •Males or non-pregnant females, 18-49 years of age, inclusive.
- •In good health*.
- •*As determined by medical history and physical examination to evaluate acute or currently ongoing chronic medical diagnoses or conditions, defined as those that have been present for at least 90 days that would affect the assessment of the safety of subjects or the immunogenicity of study vaccinations. Chronic medical diagnoses or conditions should be stable for the last 60 days. This includes no change in chronic prescription medication, dose, or frequency because of deterioration of the chronic medical diagnosis or condition in the 60 days prior to enrollment. Any prescription change that is due to change of health care provider, insurance company, etc., or that is done for financial reasons, if it is in the same class of medication, will not be considered a deviation of this inclusion criterion. Any change in prescription medication due to improvement of a disease outcome, as determined by the site principal investigator or appropriate sub-investigator, will not be considered a deviation of this inclusion criterion. Subjects may be on chronic or as needed (prn) medications if, in the opinion of the site principal investigator or appropriate sub-investigator, they pose no additional risk to subject safety or assessment of reactogenicity and immunogenicity and do not indicate a worsening of medical diagnosis or condition. Similarly, medication changes after enrollment and study vaccination are acceptable provided there was no deterioration in the subject's chronic medical condition that necessitated a medication change, and there is no additional risk to the subject or interference with the evaluation of responses to study vaccination. Note: Topical and inhaled medications (with the exception of inhaled or nasal corticosteroids within 30 days prior to enrollment), herbals, vitamins, and supplements are permitted.
- •Oral temperature is < / = 100 degrees Fahrenheit.
- •Pulse is 45 to 100 bpm, inclusive*. *Pulse can be 45 to 50 bpm, inclusive, if no other symptoms are present. Otherwise, pulse should be 50-100 bpm.
- •Systolic blood pressure is 85 to 150 mm Hg, inclusive.
- •Diastolic blood pressure is 55 to 95 mm Hg, inclusive.
- •White blood cell count is 3,900 cells/microliter or greater*.
- •*Abnormalities in white blood count, hemoglobin, platelet count, alanine aminotransferase, and serum creatinine that are suspected to be due to laboratory anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible subjects with grade 1 abnormalities in these values may be considered for enrollment if, in the opinion of the investigator (or clinician on the 1572), the abnormalities are not clinically significant and do not pose additional risk to the study or the volunteer.
- •Hemoglobin is 13.0 g/dL or greater (men) or 11.8 g/dL or greater (women)*. *Abnormalities in white blood count, hemoglobin, platelet count, alanine aminotransferase, and serum creatinine that are suspected to be due to laboratory anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible subjects with grade 1 abnormalities in these values may be considered for enrollment if, in the opinion of the investigator (or clinician on the 1572), the abnormalities are not clinically significant and do not pose additional risk to the study or the volunteer.
- •Platelet count is 135,000 cells/microliter or greater*.
- •*Abnormalities in white blood count, hemoglobin, platelet count, alanine aminotransferase, and serum creatinine that are suspected to be due to laboratory anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible subjects with grade 1 abnormalities in these values may be considered for enrollment if, in the opinion of the investigator (or clinician on the 1572), the abnormalities are not clinically significant and do not pose additional risk to the study or the volunteer.
- •Alanine aminotransferase is < 45 U/L (women) or 62 U/L (men)*.
- •*Abnormalities in white blood count, hemoglobin, platelet count, alanine aminotransferase, and serum creatinine that are suspected to be due to laboratory anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible subjects with grade 1 abnormalities in these values may be considered for enrollment if, in the opinion of the investigator (or clinician on the 1572), the abnormalities are not clinically significant and do not pose additional risk to the study or the volunteer.
- •Serum creatinine is < / = 1.25 mg/dL (men) or 1.11 mg/dL (women)*.
- •*Abnormalities in white blood count, hemoglobin, platelet count, alanine aminotransferase, and serum creatinine that are suspected to be due to laboratory anomalies may be repeated once to ensure accuracy; additionally, otherwise eligible subjects with grade 1 abnormalities in these values may be considered for enrollment if, in the opinion of the investigator (or clinician on the 1572), the abnormalities are not clinically significant and do not pose additional risk to the study or the volunteer.
- •Negative serum HIV antibody assay.
- •Women of childbearing potential* must use an acceptable contraception method** from 30 days before study vaccination until 60 days after vaccination.
- •*Not sterilized via tubal ligation, bilateral oophorectomy, salpingectomy, hysterectomy, or successful Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with documented radiological confirmation test at least 90 days after the procedure, and still menstruating or < 1 year has passed since the last menses if menopausal.
- •Includes non-male sexual relationships, abstinence from sexual intercourse with a male partner, monogamous relationship with vasectomized partner who has been vasectomized for 180 days or more prior to the subject receiving study vaccination, barrier methods such as condoms or diaphragms/cervical caps with spermicide, effective intrauterine devices, NuvaRing(R), and licensed hormonal methods such as implants, injectables or oral contraceptives ("the pill").
- •Women of childbearing potential must have a negative urine or serum pregnancy test within 24 hours prior to study vaccination.
排除标准
- •Have immunosuppression as a result of an underlying illness or treatment, or use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior to study vaccination.
- •Have known or suspected active chronic autoinflammatory condition.
- •Have known active neoplastic disease (excluding non-melanoma skin cancer) or a history of any hematologic malignancy.
- •Have a history of persistent asthma, major anatomic nasopharyngeal abnormality, or sinus polyp disease due to chronic sinusitis*.
- •*If a patient has a history of nasopharyngeal surgery such as, but not limited to rhinoplasty, tonsillectomy or sinus surgery, adequate healing time per the judgement of the investigator must occur prior to enrollment.
- •Have known hepatitis B or hepatitis C infection.
- •Have a history of alcohol or drug abuse within 5 years prior to study vaccination.
- •Currently untreated or clinically unstable (in the opinion of the investigator) schizophrenia, bipolar disease, or other psychiatric diagnosis that may interfere with subject compliance or safety evaluations.
- •Have been hospitalized for psychiatric illness, history of suicide attempt, or confinement for danger to self or others within 5 years prior to study vaccination.
- •Have received corticosteroids (including oral, parenteral, inhaled, nasal, or intra-articular) of any dose within 30 days prior to study vaccination.
- •Individual with PT serum IgG antibodies > / = 20 IU/mL and / or PRN serum IgG antibodies > / = 125 IU/ml.
- •Unwilling to refrain from smoking tobacco for 28 days post vaccination.
- •Receipt of immunoglobulin or blood derived products within 90 days of enrollment.
- •Receipt of a vaccine against pertussis in the past 2 years.
- •Receipt of a live vaccine within 30 days of study vaccination or an inactivated vaccine within 14 days of study vaccination.
- •Planned vaccination with a licensed vaccine within 28 days of study vaccination.
- •History of severe allergic reaction (e.g., anaphylaxis) or Bell's palsy, or Guillain-Barre syndrome, after a previous dose of any diphtheria toxoid-tetanus toxoid-, or pertussis-containing vaccine, or encephalopathy within 7 days of administration of a previous pertussis containing vaccine.
- •History of a progressive neurologic disorder.
- •In close contact* with children less than 1 year of age or contact with persons with known immunocompromising conditions.
- •*Close contact includes sharing a household, serving as a healthcare worker, or working professionally in settings with repeated exposures.
- •Receipt of B. pertussis-active antibiotics* within 7 days prior to vaccination.
- •*B. pertussis active antibiotics include macrolides, fluoroquinolones, trimethoprim-sulfamethoxazole, tetracyclines.
- •Known hypersensitivity to any component of the study vaccine.
- •Hypersensitivity to azithromycin, which may be used in the event of ongoing BPZE1 colonization.
- •Any condition that, in the opinion of the investigator, might interfere with objectives of the study or safety to the individual.
- •Acute illness, including temperature > 100 degrees Fahrenheit within one week prior to vaccination*.
- •Enrollment may be postponed if acute illness occurs; subjects must remain within the screening window, however, and must be rescreened if > 30 days elapses prior to enrollment.
研究组 & 干预措施
Group 1
800 microliters (10^7 CFU) of B. pertussis vaccine (BPZE1) administered intranasally with the VaxINator device on Day 1, n=15
干预措施: BPZE1 (Biological)
Group 2
800 microliters (10^9 CFU) of BPZE1 administered intranasally with the VaxINator device on Day 1, n=15
干预措施: BPZE1 (Biological)
Group 3
800 microliters of Placebo administered intranasally with the VaxINator device on Day 1, n=15
干预措施: Placebo (Other)
Group 4
800 microliters (10^9 CFU) of BPZE1 administered intranasally with a needleless tuberculin syringe on Day 1, n=5
干预措施: BPZE1 (Biological)
结局指标
主要结局
Number of Participants Experiencing Solicited Systemic Reactogenicity AEs
时间窗: Day 1 through Day 15
The solicited systemic reactogenicity events included fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and rash/hypersensitivity.
Number of Participants Experiencing Severe Solicited Local Reactogenicity Adverse Events
时间窗: Day 1 through Day 15
Solicited local reactogenicity events include runny nose, stuffy nose/congestion, nasal pain/irritation, epistaxis, sneezing, sinus pressure/pain, sore/irritated throat, cough, and shortness of breath/wheezing. They were graded as grade 1 (mild), grade 2 (moderate), or grade 3 (severe). Severe local events were those that required medical care or caused significant discomfort that prevented daily activity, including sore/irritated throat preventing eating or drinking and cough preventing sleep. Severe epistaxis events were bleeding events that required a medical encounter. Severe stuffy nose/congestion events caused the participant to be unable to breathe through the nose or to seek medical care.
Number of Participants Experiencing Serious Adverse Events (SAEs)
时间窗: Day 1 through Day 181
An adverse event was considered serious if, in the view of either the site principal investigator or sponsor, it resulted in any of the following outcomes: death, a life-threatening adverse event, inpatient hospitalization or prolongation of existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, or a congenital anomaly/birth defect, or, when, based upon appropriate medical judgment they may jeopardize the participant and may require medical or surgical intervention to prevent one of the outcomes listed in this definition.
Number of Participants Experiencing Solicited Local Reactogenicity Adverse Events (AEs)
时间窗: Day 1 through Day 15
The solicited local reactogenicity events included runny nose, stuffy nose/congestion, nasal pain/irritation, epistaxis, sneezing, sinus pressure/pain, sore/irritated throat, cough, and shortness of breath/wheezing.
Number of Participants Experiencing Adverse Events of Special Interest (AESIs)
时间窗: Day 1 through Day 29
AESIs included medically attended wheezing events given the route of study product administration and the nature of the study product.
Number of Participants Experiencing New Onset Chronic Medical Conditions (NOCMCs)
时间窗: Day 1 through Day 181
NOCMCs are defined as new medical conditions, not present at the time of screening or enrollment, that require ongoing medical care and intervention.
Number of Participants Experiencing Unsolicited Non-Serious AEs
时间窗: Day 1 through Day 29
Adverse events were defined as any untoward medical occurrence in a patient or clinical investigation participant administered a pharmaceutical product regardless of its causal relationship to the study treatment. Unsolicited non-serious AEs were documented and reported from the time of vaccination through Day 29.
Number of Participants Experiencing Severe Solicited Systemic Reactogenicity AEs
时间窗: Day 1 through Day 15
Solicited systemic reactogenicity events include fever, feverishness, fatigue, malaise, myalgia, arthralgia, headache, and rash/hypersensitivity. They were graded as grade 1 (mild), grade 2 (moderate), and grade 3 (severe). For all symptoms except rash and fever, an event was considered severe if it caused significant interference and prevented daily activity. Severe rash/hypersensitivity events were those that caused generalized urticaria, anaphylaxis, or angioedema or localized urticaria that required medical encounter. Severe fever was a temperature exceeding 38.9°C.
次要结局
- Geometric Mean Fold Rise From Screening of the Ratio of Filamentous Hemagglutinin-specific IgA (FHA-IgA) to Total IgA by Nasal Aspirate(Screening, Day 29, Day 181)
- Geometric Mean Fold Rise From Screening of the Ratio of Pertactin-Specific IgA (PRN-IgA) to Total IgA by Nasal Aspirate(Screening, Day 29, and Day 181)
- Geometric Mean Fold Rise From Screening of the Ratio of Fimbriae-Specific IgA (FIM-IgA) to Total IgA by Nasal Aspirate(Screening, Day 29, and Day 181)
- Geometric Mean Fold Rise From Baseline of Serum IgA and Serum IgG ELISA Titers to Fimbriae 2/3 (FIM)(Day 1, Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to Filamentous Hemagglutinin as Measured by Serum IgA and Serum IgG Levels(Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to Fimbriae 2/3 as Measured by Serum IgA and Serum IgG Levels(Day 15, Day 29, and Day 181)
- Geometric Mean Fold Rise From Screening of the Ratio of Pertussis Toxin-Specific IgA (PT-IgA) to Total IgA by Nasal Aspirate(Screening, Day 29, and Day 181)
- Geometric Mean Fold Rise From Baseline of Serum IgA and Serum IgG ELISA Titers to Pertactin (PRN)(Day 1, Day 15, Day 29, and Day 181)
- Geometric Mean Fold Rise From Baseline of Serum IgA and Serum IgG ELISA Titers to Pertussis Toxin (PT)(Day 1, Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to One or More Pertussis Antigens as Measured by Serum IgA or Serum IgG Levels(Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to One or More Pertussis Antigens as Measured by the Ratio of Antigen-Specific Mucosal IgA Levels to Total Mucosal IgA Levels(Day 29 and Day 181)
- Percentage of Participants With Detectable B. Pertussis From Nasopharyngeal Cultures(Day 29 and Day 46)
- Geometric Mean Titer by Serum IgA and Serum IgG to Pertactin(Day 1, Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to Two or More Pertussis Antigens as Measured by Serum IgA or Serum IgG Levels(Day 15, Day 29, and Day 181)
- Geometric Mean Titer by Serum IgA and Serum IgG to Filamentous Hemagglutinin(Day 1, Day 15, Day 29, and Day 181)
- Geometric Mean Fold Rise From Baseline Serum IgA and Serum IgG ELISA Titers to Filamentous Hemagglutinin (FHA)(Day 1, Day 15, Day 29, and Day 181)
- Geometric Mean Titer by Serum IgA and Serum IgG to Pertussis Toxin(Day 1, Day 15, Day 29, and Day 181)
- Geometric Mean Titer Ratio of Mucosal PRN-IgA to Total IgA by Nasal Aspirate(Screening, Day 29, Day 181)
- Percentage of Participants Achieving Seroconversion to Pertussis Toxin as Measured by Serum IgA and Serum IgG Levels(Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to Fimbriae 2/3 as Measured by Mucosal IgA Levels(Day 29 and Day 181)
- Geometric Mean Titer by Serum IgA and Serum IgG to Fimbriae 2/3(Day 1, Day 15, Day 29, and Day 181)
- Geometric Mean Titer Ratio of Mucosal FHA-IgA to Total IgA by Nasal Aspirate(Screening, Day 29, Day 181)
- Geometric Mean Titer Ratio of Mucosal PT-IgA to Total IgA by Nasal Aspirate(Screening, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to Filamentous Hemagglutinin as Measured by Mucosal IgA Levels(Day 29 and Day 181)
- Percentage of Participants Achieving Seroconversion to Pertussis Toxin as Measured by Mucosal IgA Levels(Day 29 and Day 181)
- Geometric Mean Titer Ratio of Mucosal FIM-IgA to Total IgA by Nasal Aspirate(Screening, Day 29, Day 181)
- Percentage of Participants Achieving Seroconversion to Pertactin as Measured by Serum IgA and Serum IgG Levels(Day 15, Day 29, and Day 181)
- Percentage of Participants Achieving Seroconversion to Pertactin as Measured by Mucosal IgA Levels(Day 29 and Day 181)