Anthrax AV7909 Liquid vs Lyophilized
Anthrax AV7909 Liquid vs Lyophilized
This is a randomized, parallel-group, double-blind, Phase 1 study designed to assess safety,
 tolerability and immunogenicity 2 formulations of adjuvanted anthrax vaccine (AV7909),
 lyophilized and liquid. Forty healthy young adults, 18 to 45 years old, inclusive, who meet
 all eligibility criteria, will be randomly allocated to one of two study groups in a 1:1
 ratio: 20 will receive AV7909 as the thermostable lyophilized product and 20 will receive
 AV7909 as the liquid product. The vaccines will be given intramuscularly in a 2-dose
 schedule, 2 weeks apart.

 Safety will be assessed by evaluation of non-serious unsolicited Adverse Events, Serious
 Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special
 Interest (AESIs) [the AESIs collected in this study are Potentially Immune-Mediated Medical
 Conditions (PIMMCs)], and by laboratory evaluations. Reactogenicity will be measured by the
 occurrence of solicited injection site and systemic reactions in the week after each study
 vaccination.

 Immunogenicity testing will include performing serological assays to assess for toxin
 neutralizing antibodies (reported as ED50 and NF50), the gold standard assay for assessing
 response and protection following anthrax vaccines, prior to vaccination and on approximately
 Days 8, 15, 22, 29, 64, 195, and 380. In addition, anti-PA IgG antibodies will be measured by
 ELISA from the serum of participants, on those same days. The primary safety objective of
 this study is to assess the safety of lyophilized and liquid formulations of AV7909. The
 primary tolerability objective is to assess the tolerability of lyophilized and liquid
 formulations of AV7909.
This is a randomized, parallel-group, double-blind, Phase 1 study designed to assess safety,
 tolerability and immunogenicity of 2 formulations of adjuvanted anthrax vaccine (AV7909),
 lyophilized and liquid. Forty healthy young adults, 18 to 45 years old, inclusive, who meet
 all eligibility criteria, will be randomly allocated to one of two study groups in a 1:1
 ratio: 20 will receive AV7909 as the thermostable lyophilized product and 20 will receive
 AV7909 as the liquid product. Stratification by age category and by gender will assure that
 near equal numbers of younger (18-30 years) and older (31-45 years) males and females are
 assigned to each vaccine. The vaccines will be given intramuscularly in a 2-dose schedule, 2
 weeks apart.

 Safety will be assessed by evaluation of non-serious unsolicited Adverse Events, Serious
 Adverse Events (SAEs), Medically Attended Adverse Events (MAAEs), Adverse Events of Special
 Interest (AESIs) [the AESIs collected in this study are Potentially Immune-Mediated Medical
 Conditions (PIMMCs)], and by laboratory evaluations. Reactogenicity will be measured by the
 occurrence of solicited injection site and systemic reactions in the week after each study
 vaccination.

 Immunogenicity testing will include performing serological assays to assess for toxin
 neutralizing antibodies (reported as ED50 and NF50), the gold standard assay for assessing
 response and protection following anthrax vaccines, prior to vaccination and on approximately
 Days 8, 15, 22, 29, 64, 195, and 380. In addition, anti-PA IgG antibodies will be measured by
 ELISA from the serum of participants, on those same days. The primary safety objective of
 this study is to assess the safety of lyophilized and liquid formulations of AV7909. The
 primary tolerability objective is to assess the tolerability of lyophilized and liquid
 formulations of AV7909. The secondary immunogenicity objective of this study is to obtain
 initial estimate of comparative immunogenicity of liquid and lyophilized formulations of
 AV7909.
Inclusion Criteria:

 1. Provide written informed consent prior to initiation of any study procedures.

 2. Understand and comply with planned study procedures, including completion of the
 electronic memory aid, and be available for all study visits.

 3. Agree to the collection of venous blood, per protocol.

 4. Have adequate venous access for phlebotomies.

 5. Be a male or non-pregnant female, 18 to 45 years of age, inclusive, at the time of
 enrollment.

 6. Be in good health.*

 * As determined by medical history and physical examination to evaluate acute or
 currently ongoing chronic medical diagnoses or conditions, which would affect the
 assessment of the safety of participants or the immunogenicity of study vaccinations.
 Chronic medical diagnoses or conditions, defined as those that have been present for
 at least 90 days, should be stable (not worsening) for the last 60 days (no
 hospitalizations, emergency room or urgent care for condition, or invasive medical
 procedure and no adverse symptoms that need medical intervention such as medication
 change indicative of worsening/supplemental oxygen). This includes no change in
 chronic prescription medication, dose or frequency, indicative of worsening disease,
 in the 60 days prior to enrollment. Any prescription change that is due to change of
 health care provider, insurance company, etc., or that is done for financial reasons,
 will not be considered a deviation of this inclusion criterion. Participants may be on
 chronic or as needed (prn) medications if, in the opinion of the site PI or
 appropriate sub-investigator, they pose no additional risk to participant safety or
 assessment of reactogenicity and immunogenicity and do not indicate a worsening or
 treatment of continued symptoms of medical diagnosis or condition. Herbals, vitamins,
 and supplements are permitted.

 7. Have an oral temperature less than 100.0 degrees Fahrenheit.

 8. Have a pulse 51 to 100 beats per minute, inclusive.

 9. Have a systolic blood pressure 85 to 140 mmHg, inclusive.

 10. Have a diastolic blood pressure 55 to 90 mmHg, inclusive.

 11. Have a calculated body mass index (BMI) less than or equal to 35.0 kg/m2 at screening.

 12. Screening laboratories are within acceptable parameters:

 -Random Glucose <110 mg/dL

 -  BUN <23 mg/dL

 -  Serum creatinine (female) <1.3 mg/dL

 -  Serum creatinine (male) < 1.4 mg/dL

 -  Alkaline phosphatase (female) <147 U/L

 -  Alkaline phosphatase (male) <192 U/L

 -  ALT (aka SGPT) <68 U/L

 -  AST (aka SGOT) (female) <45 U/L

 -  AST (aka SGOT) (male) < 60 U/L

 -  Total bilirubin < 1.3 mg/dL

 -  Hemoglobin (female) >10.9 g/dL

 -  Hemoglobin (male) > 12.4 g/dL

 -  White blood cell count 3000-12,000 cells/mm3

 -  Absolute eosinophil count <1201 cells/mm3

 -  Absolute neutrophil count >1200 cells/mm3

 -  Platelets >126,000 cells/mm3

 -  Hemoglobin A1C <6.5%

 -  Urine protein < 1+

 -  Urine glucose negative

 -  High sensitivity CRP <3.1 mg/L

 -  Urine for Drugs of Abuse (amphetamines, barbiturates, benzodiazepines, cocaine,
 methadone, opiates, oxycodone/oxymorphone, phencyclidine (PCP), and
 propoxyphene). All negative

 -  HBsAg Non-reactive

 -  HCV antibodies Negative

 -  HIV 4th generation test Negative

 13. Have no clinically significant findings on 12-lead electrocardiogram.* * Clinical
 significance will be determined by a cardiologist. Examples of findings that will lead
 to exclusion are significant left ventricular hypertrophy, right or left bundle branch
 block, advanced A-V heart block, non-sinus rhythm (excluding isolated premature atrial
 contractions), pathologic Q wave abnormalities, significant ST-T wave changes,
 prolonged QTc interval.

 14. Heterosexually active females of childbearing potential* must use an acceptable
 contraception method** from at least 30 days before the first until 60 days after the
 second study vaccination.

 *Not sterilized via bilateral oophorectomy, salpingectomy, hysterectomy, or successful
 Essure(R) placement (permanent, non-surgical, non-hormonal sterilization) with
 documented radiological confirmation test at least 90 days after the procedure, and
 still menstruating or <1 year has passed since the last menses, if menopausal.

 **Includes full abstinence from sexual intercourse with a male partner, monogamous
 relationship with vasectomized partner who has been vasectomized for 180 days or more
 or shown to be azoospermic prior to the participant receiving the study vaccination,
 barrier methods such as condoms or diaphragms/cervical cap, intrauterine devices,
 NuvaRing(R), tubal ligation, and licensed hormonal methods such as implants,
 injectables or oral contraceptives ("the pill").

 15. Females of childbearing potential must have a negative serum pregnancy test at
 screening and a negative urine pregnancy test within 24 hours prior to each study
 vaccination.

 16. For a female with potential to become pregnant, she understands that in the event of
 pregnancy during the study she will be asked to allow us to follow her during
 pregnancy through outcome.

 17. Must agree to have blood collected, stored, and potentially used for auto-antibody
 studies (if a suspected Potentially Immune-Mediated Medical Conditions (PIMMC) occurs
 in this participant).

 Exclusion Criteria:

 1. Have an acute illness*, as determined by the site principal investigator (PI) or
 appropriate sub-investigator, within 72 hours prior to study vaccination.

 *An acute illness which is nearly resolved with only minor residual symptoms remaining
 is allowable if, in the opinion of the site PI or appropriate sub-investigator, the
 residual symptoms will not interfere with the ability to assess safety parameters and
 systemic reactogenicity events as required by the protocol.

 2. Have any medical disease or condition that, in the opinion of the site PI or
 appropriate sub-investigator, is a contraindication to study participation.*

 *Including acute, subacute, intermittent, or chronic medical disease or condition that
 would place the participant at an unacceptable risk of injury, render the participant
 unable to meet the requirements of the protocol, or may interfere with the evaluation
 of responses or the participant's successful completion of this trial.

 3. Have immunosuppression as a result of an underlying illness or treatment, a recent
 history or current use of immunosuppressive or immunomodulating disease therapy.*

 *These include oral or parenteral (including intra-articular) corticosteroids of any
 dose within 30 days prior to study vaccination, or high-dose inhaled corticosteroids
 within 30 days prior to study vaccination, with high-dose defined as per age as using
 inhaled high-dose per reference chart in the National Heart, Lung and Blood Institute
 Guidelines for the Diagnosis and Management of Asthma (EPR-3) or other lists published
 in UPTODATE. Intranasal corticosteroids are not exclusionary. Low and moderate potency
 topical corticosteroids are permitted.

 4. Use of anticancer chemotherapy or radiation therapy (cytotoxic) within 3 years prior
 to study vaccination.

 5. Have known active or recently active (12 months) neoplastic disease or a history of
 any hematologic malignancy. Non-melanoma treated skin cancers are permitted.

 6. Have known human immunodeficiency virus (HIV), chronic hepatitis B, or hepatitis C
 infection.

 7. Have known hypersensitivity or allergy to any components of the study vaccines
 (Anthrax Vaccine Adsorbed (AVA), CPG adjuvants, aluminum, benzethonium chloride
 [phemerol], formaldehyde).

 8. Have a history of receipt or plan to receive, while enrolled in this study, a licensed
 or unlicensed anthrax vaccine (except for the vaccines under study herein).

 9. Have a history of Potentially Immune-Mediated Medical Conditions (PIMMCs).*

 *Adverse Events of Special Interest

 10. Have a history of alcohol or drug abuse within 5 years prior to study enrollment or
 test positive on the screening urine test for drugs of abuse.

 11. Have any diagnosis, current or past, of schizophrenia, bipolar disease, or other
 psychiatric diagnosis that may interfere* with participant compliance or safety
 evaluations.

 *As determined by the site PI or appropriate sub-investigator.

 12. Have been hospitalized for psychiatric illness, history of suicide attempt, or
 confinement for danger to self or others within 5 years prior to study vaccination.

 13. Received or plan to receive a licensed, live vaccine within 30 days before or after
 each study vaccination.

 14. Received or plan to receive a licensed, inactivated vaccine within 14 days before or
 after each study vaccination.

 15. Have a known history of documented anthrax disease or suspected exposure to anthrax.

 16. Received immunoglobulin or other blood products, except Rho(D) immunoglobulin, within
 90 days prior to study vaccination.

 17. Received an experimental agent* within 30 days prior to the study vaccination or
 expect to receive another experimental agent** during the trial-reporting period.***

 *Including vaccine, drug, biologic, device, blood product, or medication.

 **Other than from participation in this trial.

 ***Approximately 12 months after the second study vaccination.

 18. Are participating or plan to participate in another clinical trial with an
 interventional agent* that will be received during the trial-reporting period.**

 *Including licensed or unlicensed vaccine, drug, biologic, device, blood product, or
 medication.

 **Approximately 12 months after the second study vaccination.

 19. Female participants who are breastfeeding or plan to breastfeed from the time of the
 first study vaccination through 30 days after the second study vaccination.

 20. Planning to donate blood within 4 months following second vaccination.

 21. Planned elective surgery during study participation.

 22. Member or immediate family member of the site research staff found on the delegation
 log.

 23. Previously served in the military any time after 1990 and/or plan to enlist in the
 military at any time during the study.