A Phase 2 Safety and Immunogenicity Study for an Anthrax Vaccine Using 3 Schedules and Two Dose Levels

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and immunogenicity of an anthrax vaccine. The vaccine schedule and dose will also be assessed.

Detailed Description
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The safety and immunogenicity of AV7909 for post-exposure prophylaxis of anthrax will be evaluated using a randomized, parallel-group, active-controlled, double-blind design with three immunization schedules and two dose levels in healthy adult volunteers. Safety will be assessed by clinical laboratory tests (hematology, serum chemistry, and urinalysis), monitoring of adverse events, vital signs, and physical examinations. Reactogenicity (systemic and injection site reactions) will be assessed by the subjects using subject e-diaries for 7 days after each immunization and by the investigator at in-clinic visits 7 and 14 days after each immunization, and at other visits, if applicable. Immunogenicity will be measured as toxin neutralizing antibody (TNA) response and seroconversion rates.

Official Title
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A Phase 2, Randomized, Parallel-Group, Active-Controlled, Double-Blind Study to Evaluate the Safety and Immunogenicity of AV7909 for Post-Exposure Prophylaxis of Anthrax Using Three Immunization Schedules and Two Dose Levels in Healthy Adult Volunteers

Conditions
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Anthrax

Intervention / Treatment
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* Biological: AV7909
* Biological: BioThrax


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Be 18-50 years old Be in good health Have access to a computer and the internet so you can complete a diary Agree to abstain from sex the first 84 days of the study or practice birth control if you are a woman who is able to get pregnant Have not donated blood for the previous 8 weeks Exclusion Criteria: A known anaphylactic response, severe systemic response, or serious hypersensitivity reaction to a prior immunization. A history of latex allergy. Have received a shot (vaccine), including flu shots, in the past 6 weeks or plan to get a shot for 4 weeks after the last study shot is given. Have previously served in the military any time after 1990 or plan to enlist in the military from Screening through Day 84. Prior immunization with anthrax vaccine, recombinant protective antigen (rPA) vaccine, or known exposure to anthrax organisms. Have participated in anthrax therapeutic or vaccine studies (monoclonal anti-PA or anthrax immune globulins or anthrax vaccines). Participation in any investigational study involving use of a pharmacological intervention within 30 days before the Screening visit or planning to participate in a study requiring dosing through the 12-month safety follow-up telephone call. Have a known diagnosis of any immunodeficiency disease including but not limited to: acquired immune deficiency syndrome (AIDS), common variable immunodeficiency disease, immunoglobulin A (IgA) deficiency, or hypogammaglobulinemia. Past history of significant autoimmune disease such as rheumatoid arthritis, lupus erythematous, psoriasis in the area of vaccinations, or requires immunotherapy, glomerulonephritis, or autoimmune thyroiditis. Have received immunosuppressive therapy with cytotoxic drugs or Rituximab within the past 2 years. A history of cytotoxic chemotherapy or radiation therapy. Chronic (>10 days) daily oral or parenteral corticosteroid therapy in the past 12 months. Any lung disease, including reactive airway disease, which requires the daily use of medications. A female currently breastfeeding or with a positive pregnancy test. A history of drug or alcohol abuse within 12 months prior to Screening, or a positive result on a urine drug screen for cocaine, marijuana, opiates, methamphetamines, benzodiazepines, or oxycodone. Any tattoo or other skin condition in the deltoid region on either arm that may obscure the assessment of the injection sites. A medical condition that, in the opinion of the PI or designee, could adversely impact the subject's participation or safety or the conduct of the study. Any planned elective in-patient surgery during the study period.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AV7909 (Day 0 and 14)<br>Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 14 | Biological: AV7909<br>* Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant<br>* Other names: NuThrax;|
| Experimental: AV7909 (Day 0 and 28)<br>Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0 and Day 28 | Biological: AV7909<br>* Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant<br>* Other names: NuThrax;|
| Experimental: AV7909 (Day 0, 14, and 28)<br>Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 | Biological: AV7909<br>* Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant<br>* Other names: NuThrax;|
| Experimental: AV7909 Reduced Dose<br>Route of administration: Intramuscular Dose: 0.25 mL Schedule: Day 0, Day 14,and Day 28 | Biological: AV7909<br>* Anthrax Vaccine Adsorbed plus CPG 7909 Adjuvant<br>* Other names: NuThrax;|
| Active Comparator: BioThrax<br>Route of administration: Intramuscular Dose: 0.5 mL Schedule: Day 0, Day 14,and Day 28 | Biological: BioThrax<br> <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 |
| --- | --- | --- |
| Toxin Neutralizing Antibody (TNA) Level at Day 63 | Immunogenicity measured by the lower bound (LB) of the 95% confidence intervals (CIs) for the proportion of subjects in each study arm with Day 63 TNA 50% neutralization factor (NF50) values greater than or equal to threshold | Day 63 | 
| Incidence of Adverse Events | Incidence of adverse events (including assessment of symptoms, physical exam findings, clinical laboratory tests, and vital signs) from the time of the first immunization on Day 0 through Day 84 | From the time of the first immunization on Day 0 through Day 84 | 
| Incidence of Serious Adverse Events | Incidence of serious adverse events, from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination | From the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination | 
| Incidence of Reactogenicity By Severity | Incidence of solicited systemic reactions and solicited injection site reactions each day for 7 days following each vaccination using subject e-diaries by severity. Reactions were graded using the following scale (note, for redness and swelling, the diameter [greater of two perpendicular measurements] was assessed by the subject using an injection site measurement tool): Grade 0 (Absent): Symptom not present; Grade 1 (Mild): Symptom present but does not interfere with activities of daily living, or affected area (redness, swelling) measures <3 cm; Grade 2 (Moderate): Symptom causes some interference with activities of daily living, or affected area (redness, swelling) measures 3 - 10 cm; Grade 3 (Severe): Symptom prevents activities of daily living or requires treatment, or affected area (redness, swelling) measures > 10 cm. For each reaction, subjects are counted once across all vaccinations at the highest reported level of severity. | For 7 days following each vaccination on Days 0, 14, 28 | 
| Incidence of Clinical Laborabory Abnormalities | Incidence of clinical laboratory abnormalities throughout the study (up to Day 84). Clinical laboratory abnormalities are presented as the total of Grade 1 (mild), Grade 2 (moderate), Grade 3 (severe), and Grade 4 (potentially life-threatening) abnormalities according to criteria adapted from the U.S. Department of Health and Human Services, Food and Drug Administration, Center for Biologics Evaluation and Research: Guidance for Industry. Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (September 2007). Within each laboratory parameter, subjects are counted once for their most severe occurrence of clinical laboratory abnormality. | From the time of first immunization on Day 0 to Day 84 | 
| Incidence of Immunologically Significant Adverse Events of Special Interest | Incidence of immunologically significant adverse events of special interest as defined by the Center for Biologics Evaluation and Research from the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination | From the time of the first immunization on Day 0 through the 12-month safety follow-up telephone call following the last scheduled vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| TNA Level at Day 42 | Immunogenicity measured by the percentage of subjects in each study arm with Day 42 TNA NF50 values greater than or equal to threshold | Day 42 | 
| TNA Level at Day 28 | Immunogenicity measured by the percentage of subjects with Day 28 TNA NF50 values greater than or equal to threshold | Day 28 | 
| TNA Seroconversion Rate | Immunogenicity measured by the percentage of subjects who have seroconverted (defined as a 4-fold increase over Day 0 in TNA NF50 value) at Days 21, 28, 35, 42, 49, 63, and 84 | Up to Day 84 | 

 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