A Randomized Trial for the Assessment of Immunogenicity and Safety of Four Different Dosing Regimens of BioThrax® for Post-Exposure Prophylaxis for Anthrax in Adults
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 328
- 试验地点
- 4
- 主要终点
- Number of Participants With a Four-fold or Greater Increase From Baseline in Toxin Neutralization Antibody Assay (TNA) 50 Percent Neutralization Factor ( NF50 ) Antibody Titer
研究概览
简要总结
A Phase IV, randomized, multicenter trial to assess the immunogenicity and safety of BioThrax® in varying dose regimens with the primary objective of obtaining information on possible dose-sparing strategies in the event of a major biothreat.
详细描述
This is a Phase IV, randomized, open-label immunogenicity and safety study to evaluate four dosing regimens of BioThrax® for Post-Exposure Prophylaxis (PEP) for anthrax. BioThrax® will be administered as a subcutaneous (SC) injection for the primary series and will be administered as an intramuscular (IM) injection for the boost. The four dosing regimens are: 0.50mL BioThrax® on Days 0, 14, and 6 month boost; 0.50mL BioThrax® on Days 0, 28 and 6 month boost; 0.50mL BioThrax® on Days 0, 14, 28 and 6 month boost and 0.25mL BioThrax® on Days 0, 14, and 28, 6 month boost with 0.50ml IM Approximately 300 subjects will be randomized 1:1:1:1 to one of the four study arms. Enrollment will be stratified by gender, with approximately equal numbers of males and females (18 through 65 years) enrolled into each dosing regimen. The Primary objective is to evaluate the immunogenicity of the four dosing regimens of BioThrax® using the Toxin Neutralization Assay (TNA). The secondary objective is to evaluate the safety of the four dosing regimens of BioThrax®.
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
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Subject able to provide informed consent;
- •Female or male, 18 through 65 years of age, inclusive;
- •If the subject is female and of childbearing potential, she agrees to practice abstinence from sexual intercourse with men (vaginal penetration by a penis, coitus) or use acceptable contraception, initiated at least 30 days prior to the first study vaccination through 56 days after the 6 month boost vaccination in order to avoid pregnancy:
- •A woman is considered of childbearing potential unless post-menopausal (>/= 1 year without menses) or surgically sterilized (tubal ligation, bilateral oophorectomy, or hysterectomy)
- •Acceptable contraception methods are restricted to effective devices (IUDs, NuvaRing®) or licensed hormonal products with use of method for a minimum of 30 days prior to vaccination, condoms with spermicidal agents, monogamous relationship with a vasectomized partner who has been vasectomized for 6 months or more prior to study entry, or successful Essure placement with documented confirmation test at least 3 months after the procedure, and any other Food and Drug Administration (FDA)-approved contraceptive method
- •Be willing and able to return for all visits and blood collections for the duration of the study;
- •Be able to understand and comply with planned study procedures;
- •Agree to complete the memory aid and to report concomitant medications and Adverse Events during the study period.
- •Further clarification of inclusion/
排除标准
- •Provided a subject meets all study inclusion criteria and none of the study exclusion criteria, the following conditions will not exclude the subject from study participation:
- •* History of gestational diabetes;
- •* Type II diabetes controlled with diet or oral hypoglycemic medications;
- •* Treated, controlled, uncomplicated hypertension;
- •* History of coronary artery disease, asymptomatic (New York Heart Association \[NYHA\] Function Class I), on a stable medical regimen. Persons meeting these criteria must be at least two years post-myocardial infarction, cardiac bypass surgery and/or percutaneous coronary interventions (e.g., angioplasty, stent placement) in order to qualify. Persons with a history of cardiac disease must be under the care of a physician;
- •* Cured, non-metastatic cancer (excluding hematologic malignancies), disease-free for five years;
- •* Localized skin cancer, resected (including squamous cell and basal cell carcinomas). Participants with a history of melanoma must be disease-free for five years;
- •* Exercise-induced bronchospasm controlled with inhaled medication(s) only;
- •* Mild asthma: Subjects who have not been hospitalized for asthma in the past two years and use only inhalers to control their symptoms will be eligible. Only low to medium doses of inhaled steroids, defined as \100.4 F within 3 days prior to vaccination;
- •* Have a blood pressure, heart rate or respiratory rate of Grade 2 or higher;
- •* Have any chronic condition that, in the opinion of the Investigator, would render vaccination unsafe or would interfere with study evaluations or completion of the study;
- •* Have a total White Blood Cell (WBC) count, Absolute Neutrophil Count (ANC), hemoglobin or platelet count that is Grade 2 or higher;
- •* Have a creatinine higher than the normal range;
- •* Have an Alanine Aminotransferase (ALT) of \>/= 1.2 x Upper Limit of Normal;
- •* Have a value higher than trace for glucose and/or protein on urinalysis;
- •* Have a history of hospitalization for psychiatric illness, suicide attempt, or confinement for danger to self or others, within the past 10 years. (Subjects with a psychiatric disorder \[not meeting exclusion criteria, e.g. attention-deficit hyperactivity disorder\] that is controlled for a minimum of 3 months and the investigator has determined that the subject's mental status will not compromise the subject's ability to comply with protocol requirements may be enrolled);
- •* Be taking any of the following psychiatric drugs: aripiprazole, clozapine, ziprasidone, haloperidol, molindone, loxapine, thioridazine, thiothixene, pimozide, fluphenazine, risperidone, mesoridazine, quetiapine, trifluoperazine, trifluopromazine, chlorprothixene, chlorpromazine, perphenazine, olanzapine, carbamazepine, divalproex sodium, lithium carbonate or lithium citrate;
- •* Be taking more than one antidepressant drug not included in the list above (subjects taking only one antidepressant drug \[not listed in excluded psychiatric drugs\] who are stable for at least 3 months prior to enrollment without decompensating are allowed enrollment into the study provided the investigator determines the subject's mental status will not compromise the subject's ability to comply with protocol requirements);
- •* Have donated blood within 30 days of enrollment or plans to donate blood during the study.
- •* Have a tattoo in the area of the vaccination sites which will interfere with the assessment of injection site reactogenicity.
研究组 & 干预措施
Arm B: 0.50mL BioThrax®
BioThrax® 0.50mL subcutaneously on Days 0, 28 and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects
干预措施: BioThrax® (Biological)
Arm C: 0.50mL BioThrax®
BioThrax® 0.50mL subcutaneously on Days 0, 14, 28 and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects
干预措施: BioThrax® (Biological)
Arm D: 0.25mL BioThrax®
BioThrax® 0.25mL subcutaneously on Days 0,14, and 28,and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects
干预措施: BioThrax® (Biological)
Arm A: 0.50mL BioThrax®
BioThrax® 0.50 ml subcutaneously on Days 0, 14, and 0.50mL BioThrax® intramuscular 6 month boost; 75 subjects
干预措施: BioThrax® (Biological)
结局指标
主要结局
Number of Participants With a Four-fold or Greater Increase From Baseline in Toxin Neutralization Antibody Assay (TNA) 50 Percent Neutralization Factor ( NF50 ) Antibody Titer
时间窗: Days 0, 7, 14, 21, 28 35, 42, 49, 56, 63, 70, 84 and 100
Blood was collected from all participants prior to vaccination and at scheduled follow up visits weekly through Day 70, at Day 84 and at Day 100 for testing in the toxin neutralization antibody assay to determine the NF50 antibody titer. A participant met the threshold of a 4-fold rise in NF50 antibody titer if the post vaccination titer was an increase by 4-fold or more from the baseline (Day 0) titer.
次要结局
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 0 by Maximum Severity(Days 0-7 after vaccination at Day 0)
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following the 6-month Boost by Maximum Severity(Days 0-7 after vaccination at Month 6)
- Peak Geometric Mean Concentration (GMC) of ELISA Anti-PA IgG Antibody Through Day 100(Day 7 through Day 100)
- Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 0 by Maximum Severity.(Days 0-7 after vaccination at Day 0)
- Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 0 by Maximum Severity(Day 0-7 after vaccination at Day 0)
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 14 by Maximum Severity(Days 0-7 after vaccination at Day 14)
- Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 14 by Maximum Severity.(Days 0-7 after vaccination at Day 14)
- Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 28 by Maximum Severity(Day 0-7 after vaccination at Day 28)
- Geometric Mean Concentration (GMC) of Enzyme-linked Immunosorbent Assay (ELISA) Antibody Against the Protective Antigen (Anti-PA IgG)(Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.)
- Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After Vaccination at Day 28 by Maximum Severity.(Days 0-7 after vaccination at Day 28)
- Number of Participants Reporting Fever in the Eight Days After the 6-month Boost Vaccination by Maximum Severity(Day 0-7 after vaccination at Month 6)
- Number of Subjects With a Four-fold or Greater Increase From Baseline in Enzyme-linked Immunosorbent Assay (ELISA) Antibody Concentration Against the Protective Antigen (Anti-PA IgG)(Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.)
- TNA NF50 Peak Geometric Mean Titer (GMT) Antibody Response Through Day 100(Day 7 through Day 100)
- Number of Participants Reporting Solicited Injection Site Reactogenicity Symptoms in the Eight Days Following Vaccination at Day 28 by Maximum Severity(Days 0-7 after vaccination at Day 28)
- Number of Participants With Injection Site Edema and Erythema With a Size of Greater Than 120 Millimeters (mm)(Days 0-7 after each vaccination)
- TNA NF50 Geometric Mean Titers (GMT) at Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.(Days 0, 7, 14, 21, 28, 35, 42, 49, 56, 63, 70, 84 and 100.)
- Number of Participants Reporting Solicited Subjective Systemic Symptoms for Eight Days After the 6-month Boost Vaccination by Maximum Severity.(Days 0-7 after vaccination at Month 6)
- Number of Participants Reporting Fever in the Eight Days After Vaccination at Day 14 by Maximum Severity(Day 0-7 after vaccination at Day 14)