Assessment of the Immunogenicity and Safety of a Dose-Sparing BioThrax® AVA Schedule
Condition: Bacillus Anthracis (Anthrax)
MeSH terms: Anthrax
Intervention: BioThrax®; BioThrax®
Intervention description: BioThrax® is a sterile, milky white suspension made from cell free filtrates of microaerophilic cultures of an avirulent, nonencapsulated strain of Bacillus anthracis, will be administered as a 0.50mL IM injection 6 month boost for all groups; BioThrax® will be administered as: Arm A: 0.50mL SC injection on Days 0 and 14; Arm B: 0.50mL SC injection on Days 0 and 28; Arm C: 0.50mL SC injection on Days 0, 14 and 28; Arm D: 0.25 mL SC injection on Days 0, 14 and 28.
Phase: Phase 4
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 328.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Bacillus anthracis, anthrax, vaccine, BioThrax®, dose-sparing

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  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:

               1. A woman is considered of childbearing potential unless post-menopausal (>/= 1
                  year without menses) or surgically sterilized (tubal ligation, bilateral
                  oophorectomy, or hysterectomy)

               2. 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/exclusion criteria:

        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 </=3 puffs a day, are allowed. Persons who
             require oral or parenteral steroids will not be eligible.

          -  Subjects with isolated entrapment neuropathies, such as carpal tunnel syndrome, or
             compression neuropathies, such as lumbar radiculopathy, that are not associated with
             systemic disease or immune dysfunction may be eligible for enrollment. If the
             subject's condition has been stable for six months, surgery is not planned for the
             condition, the neurologic examination is normal (specifically no weakness or
             paresthesias), and the mononeuropathy will not interfere with the assessment of
             reactogenicity, the subject is eligible.

          -  Subjects with vitiligo who are otherwise healthy and the vitiligo is not widespread in
             the area of the vaccinations may be eligible for enrollment.

          -  Subjects with seasonal allergies are eligible provided the dose of nasal steroids that
             are used is < 800µg/day.

        Exclusion Criteria:

          -  Have a prior history of anthrax or immunization against anthrax;

          -  Intend to enlist in the military during the study;

          -  Have a known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or
             latex;

          -  (Females only) Be pregnant, plan to become pregnant at any time between the Screening
             Visit through 56 days after the 6 month boost vaccination, or refuse to use/not have
             used an acceptable method of birth control (see Inclusion Criterion 3) from 30 days
             prior to the first study vaccine dose through 56 days after the 6 month boost
             vaccination;

          -  Have received experimental products within 30 days before study entry or plan to
             receive experimental products at any time during the study;

          -  Have received a live vaccine within 30 days before study entry or plan to receive a
             live vaccine prior to Day 63 of the study or within 30 days of the 6 month boost;

          -  Have received an inactivated vaccine within 14 days before study entry or plan to
             receive an inactivated vaccine from Day 0 to Day 42 or within 14 days of the 6 month
             boost;

          -  Have received immunosuppressive therapy (including systemic steroids) within 3 months
             prior to study entry or plan to receive immunosuppressive therapy at any time during
             the study;

          -  Have received cytotoxic therapy in the previous 5 years or plan to receive cytotoxic
             therapy at any time during the study;

          -  Have received parenteral immunoglobulin or blood products within 3 months of the study
             or plan to receive parenteral immunoglobulin or blood products at any time during the
             study;

          -  Have a history of Guillain-Barré Syndrome;

          -  Have an active malignancy or history of metastatic or hematologic malignancy;

          -  Have Type I diabetes or Type II diabetes treated with insulin;

          -  Have cardiovascular disease (including any person with a history of cardiomyopathy or
             congestive heart failure);

          -  Have moderate to severe asthma, chronic obstructive pulmonary disease or other
             significant pulmonary disease;

          -  Have hepatic or renal insufficiency;

          -  Have an autoimmune, inflammatory, vasculitic or rheumatic disease including but not
             limited to systemic lupus erythematosus, polymyalgia rheumatica, rheumatoid arthritis
             or scleroderma;

          -  Have HIV, hepatitis B or hepatitis C infection;

          -  Have any other condition known to produce or be associated with immunosuppression;

          -  Have neuropathy or any other evolving neurological condition;

          -  Have an ongoing drug abuse/dependence (including alcohol) issues or a history of these
             issues within five years of enrollment;

          -  Have a seizure disorder;

          -  Have moderate or severe illness and/or an oral temperature >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.