BARDA Securing Anthrax Immunity For the Elderly
Condition: Anthrax
MeSH terms: Anthrax
Intervention: BioThrax; AV7909; Sodium chloride injection USP, 0.9% (placebo)
Intervention description: Other Names:
Anthrax Vaccine Adsorbed (AVA); Anthrax Vaccine Absorbed plus CPG 7909 Adjuvant; Other Names:
Saline Solution
Intervention MeSH terms: Vaccines
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Subjects will be randomized to receive either BioThrax or AV7909. Randomization will be stratified by sex and age (18-50, 66-74, and ≥75 years). Subjects ≥66 years of age will be randomized 1:1:1:1 within stratum across 4 treatment arms (approximately 50 subjects per group), and subjects 18 through 50 years of age will be randomized 1:1 within stratum across 2 treatment arms (approximately 50 subjects per group). Once randomized, subjects will receive 3 vaccinations, each separated by approximately 14 days, on Day 1, Day 15, and Day 29, based on their assigned treatment arm.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 305.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Anthrax; Bacillaceae Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Anthrax Vaccine Adsorbed; BioThrax; AV7909; CPG 7909; Adjuvant; Vaccines; Post-exposure Prophylaxis

Summary:

      This study is designed to assess the safety and ability of BioThrax and AV7909 anthrax
      vaccines to generate an immune response in adults ≥ 66 years of age in stable health in
      comparison to adults 18-50 years of age in stable health.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Male or nonpregnant females, 66 years of age or older at the time of randomization for
             the elderly population, or 18 through 50 years of age at the time of randomization for
             the younger population.

          2. Females who are of childbearing potential and are sexually active with a male partner
             must agree to use an acceptable method of birth control from Screening to Day 64 and
             must have used a reliable birth control method for at least 2 months prior to
             Screening.

               1. A female of childbearing potential is defined as post onset menarche and
                  pre-menopausal female capable of becoming pregnant. This does not include females
                  who meet any of the following conditions: menopausal >2 years, tubal ligation >1
                  year, bilateral salpingo-oophorectomy, or hysterectomy.

               2. Adequate contraception is defined as a contraceptive method with a failure rate
                  of less than 1% per year when used consistently and correctly and when
                  applicable, in accordance with the product label. Examples include: oral
                  contraceptives, either combined or progestogen alone; injectable progestogen;
                  implants of etenogestrel or levonorgestrel; estrogenic vaginal ring; percutaneous
                  contraceptive patches; intrauterine device or intrauterine system; male partner
                  sterilization at least 6 months prior to the female subject's Screening Visit,
                  and this male is the sole partner for that subject (the information on the male
                  partner's sterility can come from the site personnel's review of the subject's
                  medical records or interview with the subject on her medical history); male
                  condom combined with a vaginal spermicide (foam, gel, film, cream, or
                  suppository); male condom combined with a female diaphragm, either with or
                  without a vaginal spermicide (foam, gel, film, cream, or suppository).

          3. Able to provide written informed consent prior to initiation of any study procedures.
             As part of the consent process, subjects must be able to demonstrate understanding by
             passing the "Assessment of Understanding Questionnaire" within 2 attempts. Passing is
             defined as being able to answer all questions correctly.

          4. In relatively stable health based on site investigator's judgment, as determined by
             medical history, physical examination, and the following criteria:

               1. Stable health for age (defined as no new conditions per medical history, new
                  medications in a different therapeutic class, or change in daily dose of existing
                  prescription medications within the 45 days preceding Screening). Effective
                  treatment (to resolution) of an acute infection (e.g., urinary tract infection,
                  cellulitis, otitis, or bronchitis) with an antibiotic within 45 days preceding
                  Screening will not be considered a deviation from this inclusion criterion as
                  long as the antibiotic therapy was completed at least one week prior to Screening
                  and no signs or symptoms of the infection have been present since the completion
                  of treatment. Any prescription change that is due to change of health care
                  provider or insurance company, or that is made for reasons that do not reflect a
                  change in disease status (e.g., financial considerations), as long as within the
                  same general class of medication, will not be considered a deviation from this
                  inclusion criterion. Any change in prescription medication due to improvement of
                  a disease outcome, as determined by the site investigator, will not be considered
                  a deviation from this inclusion criterion.

               2. Subjects may be on chronic or as needed (prn) medications if, in the opinion of
                  the site investigator, these pose no additional risk to subject safety or
                  assessment of reactogenicity and immunogenicity and their use is not for
                  management of a worsening of medical diagnosis or condition. Note: Topical,
                  nasal, and inhaled medications (with the exception of steroids, as outlined in
                  the subject exclusion criteria) and vitamins are permitted.

          5. Have a body mass index (BMI) less than 35.0 kg/m2 at Screening. (BMI will not be
             reassessed prior to subsequent vaccinations.)

          6. Have access to a consistent and reliable means of telephone contact, which may be
             home, workplace, or by personal mobile electronic device.

          7. Are available and able to comply with all study visits.

        Exclusion Criteria:

          1. Females who have a positive urine pregnancy test at Screening or within 24 hours prior
             to each study vaccination or women who are breastfeeding.

          2. Have a requirement for skilled nursing care.

          3. Have a history of severe reactions to components of AVA or CPG 7909, e.g.,
             formaldehyde, benzethonium chloride (phemerol), or aluminum.

          4. Have a history of latex sensitivity.

          5. Have a history of ever receiving a vaccine for anthrax prior to Screening, or had an
             anthrax infection.

          6. Have any medical, psychiatric, or social condition that, in the opinion of the site
             investigator, unfavorably alters the risk-benefit of subject participation, or is
             likely to interfere with study compliance or assessments, or is likely to confound
             interpretation of safety or immunogenicity data.

          7. Have any diagnosis, current or past, of a potentially immune-mediated medical
             condition, such as Guillain-Barré syndrome, narcolepsy, or an autoimmune or chronic
             inflammatory disease.

          8. Have any diagnosis, current or past, of schizophrenia or bipolar disorder.

          9. Have been hospitalized for psychiatric illness, have a history of suicide attempt, or
             confinement for danger to self or others within the preceding 10 years prior to
             Screening and each study vaccination.

         10. Have a history of alcohol or drug abuse (per investigator's judgment) within 5 years
             prior to Screening and each study vaccination, or test positive for drugs of abuse at
             Screening (including for cannabis, even where legal). Benzodiazepines for anxiety
             disorders and stimulants for attention deficit hyperactivity disorder are not
             exclusionary if the subject has been on a stable dose for more than 3 months prior to
             Screening and each study vaccination and if the subject can produce a valid, current
             prescription for the medication. Propoxyphene, opioids, or combinations containing
             these medications (including as used for opioid addiction) are not permitted
             regardless of prescription status. Note: A positive Screening urine drug screen may
             not be repeated. (Drug screen will not be repeated prior to subsequent vaccinations.)

         11. Have known human immunodeficiency virus (HIV), or acute or chronic hepatitis B or
             hepatitis C infection based on medical history; or test positive for any of these at
             Screening. Subjects who have been effectively treated for hepatitis C, as evidenced by
             a negative hepatitis C ribonucleic acid (RNA) confirmation test and who no longer
             require antiviral therapy, are eligible for participation. (Screening tests will not
             be repeated prior to subsequent vaccinations.)

         12. Have known active neoplastic disease or a history of any hematologic malignancy.
             However, subjects with superficial skin cancer who do not require intervention other
             than local excision are not excluded.

         13. Have immunosuppression as a result of an underlying illness or treatment, or use of
             anticancer chemotherapy (cytotoxic) or radiation therapy within 3 years prior to
             Screening and each study vaccination.

         14. Have taken any systemic immunosuppressive agents, including immunomodulators, 6 months
             prior to Screening and each study vaccination. Allergen immunotherapy
             (desensitization) is not exclusionary. Allergen immunotherapy (desensitization) does
             not include systemic antibodies such as benralizumab, mepolizumab, or omalizumab;
             these are exclusionary.

         15. Are suffering from or have a history of neuralgia, paresthesia, or neuritis within 90
             days prior to Screening and each study vaccination; or have any history of stroke.

         16. Have had convulsions or encephalomyelitis within three years prior to Screening and
             each study vaccination.

         17. Have received immunoglobulin or other blood products (with the exception of Rho[D]
             immune globulin) within 90 days prior to Screening and each study vaccination.

         18. Have received an experimental agent within 180 days prior to the first study
             vaccination, or expects to participate in another clinical trial with an
             interventional agent during the study period. This includes licensed or unlicensed
             vaccines, drugs, biologics, devices, blood products, or medications. Participation in
             an observational study is not exclusionary as long as it doesn't interfere with study
             visits or procedures (e.g., blood collection volume restrictions).

         19. Have taken oral or parenteral corticosteroids of any dose within 30 days prior to each
             study vaccination.

         20. Have taken high-dose inhaled corticosteroids within 30 days prior to each study
             vaccination. High-dose is defined as >800 mcg/day of beclomethasone dipropionate or
             equivalent. Lower doses of inhaled corticosteroids are not exclusionary.

         21. Have received any licensed live vaccine within 30 days prior to the first study
             vaccination or planned receipt from the first study vaccination through Visit 10 (Day
             64).

         22. Have received any licensed inactivated vaccine within 14 days prior to the first study
             vaccination or planned receipt from the first study vaccination through Visit 10 (Day
             64).

         23. Have an acute illness, as determined by the site investigator, within 72 hours prior
             to each study vaccination.

               1. If subject's oral temperature is above 100.0°F (37.8°C), the subject may be
                  re-assessed for eligibility within the visit window (+3 Days).

               2. An acute illness that is nearly resolved, with only minor residual symptoms
                  remaining, is allowable if, in the opinion of the site investigator, the residual
                  symptoms will not interfere with the ability of study staff to assess safety
                  parameters as required by the protocol.

               3. For bacterial infections that have been successfully treated with antibiotics,
                  inclusion criterion 4a applies.

         24. Have a history of myocardial infarction or ischemia, or have electrocardiogram (ECG)
             findings of myocardial infarction, ischemia, strain, complete bundle branch block, or
             ventricular arrhythmias (other than unifocal premature ventricular contractions
             ≤2/minute). Additionally, other cardiac history or ECG findings, which in the opinion
             of the investigator represent a potentially unstable or unacceptably high risk of an
             adverse cardiac outcome, are exclusionary. (ECG will not be repeated prior to
             subsequent vaccinations.)

         25. Have any laboratory test result or clinical findings (including vital signs) that
             singly or in combination are, in the investigator's opinion, likely to unfavorably
             alter the risk-benefit of subject participation or to confound study safety or
             immunogenicity results. Additionally, the following are exclusionary:

               1. Any clinically significant Grade 3 laboratory or vital sign result, or any Grade
                  4 laboratory or vital sign result (regardless of assessed significance) at
                  Screening. For subsequent vaccinations, abnormal laboratory results and vital
                  sign results postvaccination will be assessed against the rules for early
                  termination of dosing.

               2. Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >2 times the
                  upper limit of normal (ULN), or bilirubin >1.5 times the ULN unless isolated
                  Gilbert's syndrome.

               3. Creatinine >1.5 times ULN for age and sex.

               4. White blood cell count <3,000/μL or >12,500/μL; absolute neutrophil count
                  <1200/μL; absolute lymphocyte count <750/μL; hemoglobin <10 g/dL females, or
                  <11.5 g/dL males; platelet count <75,000/μL.

               5. Hemoglobin A1C (HbA1C) >7.0% at Screening. (HbA1C will not be repeated prior to
                  subsequent vaccinations.)

        Subjects cannot be rescreened for exclusionary laboratory test results. Potentially
        exclusionary vital sign results may be repeated, but unless they have resolved to a Grade 3
        designation or less and are not considered clinically significant, the subject should be
        excluded. The most recent laboratory and vital sign results will be used when determining
        eligibility for subsequent vaccinations.