A Phase 1, Randomized, Parallel-Group, Double-Blind Trial of AV7909 (Liquid) and Thermostable AV7909 (Lyophilized) in Healthy Adult Volunteers
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.
• Provide written informed consent prior to initiation of any study procedures.
• Understand and comply with planned study procedures, including completion of the electronic memory aid, and be available for all study visits.
• Agree to the collection of venous blood, per protocol.
• Have adequate venous access for phlebotomies.
• Be a male or non-pregnant female, 18 to 45 years of age, inclusive, at the time of enrollment.
• 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.
• Have an oral temperature less than 100.0 degrees Fahrenheit.
• Have a pulse 51 to 100 beats per minute, inclusive.
• Have a systolic blood pressure 85 to 140 mmHg, inclusive.
⁃ Have a diastolic blood pressure 55 to 90 mmHg, inclusive.
⁃ Have a calculated body mass index (BMI) less than or equal to 35.0 kg/m2 at screening.
⁃ Screening laboratories are within acceptable parameters:
∙ 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
‣ 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 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
⁃ 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.
⁃ 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).
⁃ 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.
⁃ 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.
⁃ 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).