Immunogenicity and Safety Study of a Three-Dose BioThrax® Regimen for Post-Exposure Prophylaxis in Healthy Adults

Study Overview
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Brief Summary
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The purpose of this Phase 3 clinical trial is to evaluate the immunogenicity and safety of BioThrax anthrax vaccine in healthy adults following 3 doses of BioThrax. Results of this study will be used to support a post-exposure prophylaxis (PEP) indication for BioThrax. This study will be conducted in the United States (U.S.), in 200 healthy male and female volunteer subjects ages 18 to 65 years. The duration of study participation for each individual subject will be approximately 128 days (4.25 months), including a screening period of approximately 28 days followed by 100 days on study.

Detailed Description
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BioThrax® (also called Anthrax Vaccine Adsorbed or AVA) is the only FDA-licensed vaccine for the prevention of anthrax infection. This study will evaluate the immunogenicity of the vaccine using a post-exposure vaccination schedule. Correlations will be drawn to immunogenicity and survival data from animal models to demonstrate that BioThrax® can elicit a protective immune response for PEP.

Official Title
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Immunogenicity and Safety Study of a Three-Dose BioThrax® Regimen for Post-Exposure Prophylaxis in Healthy Adults

Conditions
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Anthrax

Intervention / Treatment
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* Biological: BioThrax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be between 18 and 65 years of age, inclusive, at the time of enrollment. Be in good health as determined by the investigator from medical history and a physical examination. If a pre-menopausal female, must be using acceptable methods of birth control. Have all hematology and chemistry parameters (measured at Screening) within the laboratory's normal range. Be willing and able to return for all visits and blood collections for the duration of the study. Have read, understood and signed an informed consent form. Exclusion Criteria: Prior immunization with anthrax vaccine or known exposure to anthrax organisms. Intend to enlist in the military during the study. Have a known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex. Plan to receive experimental products at any time during the study. Have received a live vaccine in the 30 days before study entry. Plan to receive a live vaccine at any time during the study. Have ongoing drug abuse/dependence (including alcohol) issues and/or test positive in a urine drug screen for amphetamines, barbiturates, cocaine or opiates; Have received immunosuppressive therapy (including systemic steroids) within 3 months prior to study entry. Have a condition known to produce or be associated with immunosuppression. Have received cytotoxic therapy in the previous 5 years. A medical condition that, in the opinion of the Principal Investigator (PI), could adversely impact the subject's participation, safety, or conduct of the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BioThrax (0.5 mL, on days 0, 14, and 28)<br> | Biological: BioThrax<br>* BioThrax, 0.5 mL administered subcutaneously on days 0, 14, and 28.<br>* Other names: Anthrax Vaccine Adsorbed (AVA);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 63 (5 Weeks Following the Third Vaccination on Day 28). | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Day 63 +/- 2 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value at Day 70. | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Day 70 +/- 2 days | 
| Average Percentage of Subjects Achieving a TNA Response of a Predefined Threshold Value Between Days 63 and 100 (Inclusive). | Neutralizing antibody levels in blinded serum samples were measured using a validated anthrax lethal toxin neutralization assay. The primary assay endpoint was the 50% neutralization factor (TNA NF50), which is calculated as the ratio of the 50% effective dose (ED50) of the test sample to the ED50 of a reference serum. | Days 63 to 100 | 
| Incidence of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). | 
| Percentage of Injection Site Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Injection site reactions (warmth, tenderness, itching, pain, arm motion limitation, redness, lump, swelling, and bruise) were evaluated by using a web-enabled subject diary. Subjects assessed the severity of warmth, tenderness, itching, pain, arm motion limitation, lump, and bruise as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of redness and swelling were based on the diameter of the affected area. Severe injection site reactions were recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). | 
| Incidence of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). | 
| Percentage of Systemic Reactions by Severity (Mild, Moderate, Severe) From Subject Diary Cards | Systemic reactions (fatigue/ tiredness, muscle ache, headache, and fever) were evaluated by using a web-enabled subject diary. Subjects assessed severity as absent, mild, moderate, or severe based on the degree of interference with daily activities. Severity of fever was assessed using a grading scale. Severe systemic reactions were to be recorded as adverse events by the investigator site staff after confirmation with the subject. | Web-enabled diaries were completed for 7 days after each of three injections (Days 0, 14, and 28). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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post-exposure prophylaxis, toxin neutralization assay