Velocity 2: An Anthrax Vaccine and Antibiotics Clinical Study

This is a Phase 2, open-label, multicenter, randomized trial designed to evaluate the pharmacokinetic profile, immunogenicity, and safety of AV7909 and ciprofloxacin or doxycycline when administered concomitantly in healthy adults for an indication of post-exposure prophylaxis (PEP) of anthrax.

Healthy adults between 18 to 45 years of age (inclusive) will sign and date an informed consent form and then be screened for eligibility for participation in the study 2 to 28 days prior to randomization. Participants meeting the entry criteria will be randomized 1:1:1 to one of the three study groups (AV7909 + ciprofloxacin, AV7909 + doxycycline and AV7909 only) on Day 1.

Subjects randomized into Groups 1 & 2 will be assigned to subgroups. Subgroup A will be assigned to the antibiotic PK treatment group first, while subgroup B will be assigned to the antibiotic non-PK treatment group.

Participants will be evaluated for safety through Day 51 [or the early withdrawal visit (EWV)], as assessed by clinical laboratory tests (hematology, serum chemistry, and urinalysis), monitoring of Adverse Events (AEs) including Serious Adverse Events (SAEs) and Adverse Events of Special Interest (AESIs), vital signs, and physical examinations. Adverse Events of Special Interest are adverse events associated with autoimmune disease as defined by the Center for Biologics Evaluation and Research, and might represent a safety signal for vaccine-associated autoimmunity. Reactogenicity (solicited systemic and injection site reactions) will be assessed daily by the participants using electronic diaries (e-diaries) after each vaccination. The e-diary will also be used to record self-administration of antibiotics for applicable study groups.

Information on the use of medications will be collected at each study visit. In addition, blood samples for auto-antibody assessment will be taken at Day 1 pre-dose and Day 51 (or Early Withdrawal Visit).

Participants who receive at least one dose of vaccine will also be asked to participate in safety follow-up phone calls occurring on Month 3, Month 6, Month 9, and Month 12 (nominally 3, 6, 9, and 12 months after the last vaccination) to collect information on AEs, SAEs and any potential AESIs. Based on responses at these phone contacts, participants may be asked to return to the clinic for an unscheduled visit to provide blood samples for auto-antibody testing to investigate reports of potential AESIs.

Independent safety oversight will be provided by a Data Safety Monitoring Board, which will be notified of significant AEs, potential AEsIs, or any other events as determined by the Medical Monitor, on an ongoing basis.

Inclusion criteria

• Written informed consent obtained from the participant (dated, signed, and captured in the medical chart at the site).
• A male or female, aged 18 to 45 years of age, inclusive, at the time of informed consent.
• Healthy condition as established by medical history and clinical examination before entering into the study.
• Body mass index (BMI) less than or equal to 35.0 kg/m^2 at the Screening visit.
• Have adequate venous access for phlebotomies.
• For a woman of childbearing potential (WOCBP), negative pregnancy test at Screening and pre-randomization on Day 1, not currently breastfeeding, and no intention to become pregnant during the study period through 12 months after last receipt of any investigational product (IP). Every female participant is considered to be a WOCBP unless she is surgically sterile (hysterectomy, bilateral salpingectomy or bilateral oophorectomy) OR postmenopausal (defined as >12 consecutive months without menses and screen follicle-stimulating hormone > 30 mIU/mL). Women who are not of childbearing potential are allowed to enroll if they are surgically sterile or postmenopausal as defined above.

Female participants randomized to Groups 1 or 2 must be willing to add a double-barrier method, IUD, or abstinence as back-up forms of birth control since ciprofloxacin and doxycycline may decrease the effectiveness of birth control pills, implantable or injectable contraceptives.

Exclusion criteria

• A Screening clinical laboratory test result greater than the central laboratory's upper limit of normal (ULN) for aspartate aminotransferase (AST), alanine aminotransferase (ALT), random glucose, total bilirubin, blood urea nitrogen (BUN), or creatinine. Other serum chemistry parameters that are not within the reference range will not be considered exclusionary unless deemed clinically significant by the principal investigator.
• History of allergic reaction or intolerance to quinolone antimicrobials or any medical condition that would contraindicate the use of ciprofloxacin, including and not limited to vascular disorders, tendon disorders, certain genetic connective tissue disorders (e.g., Marfan and Ehlers-Danlos syndrome), prolongation of QT interval, seizures, peripheral neuropathy, increased risk of C. difficile infection.
• History of allergic reaction or intolerance to tetracycline antibiotics or any medical condition that would contraindicate the use of doxycycline including an increased risk of C. difficile infection, increases in BUN or an increased sensitivity to direct sunlight or ultraviolet radiation resulting in erythema.
• Has a need for any of the prohibited medications or requires the medications/foods within the prohibited times.
• Have a tattoo/scar/birthmark or any other skin condition affecting the deltoid area that may interfere with injection site assessments.
• History of anthrax disease, suspected exposure to anthrax, or previous vaccination with any anthrax vaccine.
• Have previously served in the military any time after 1990 or plan to enlist in the military any time from Screening through the final telephone contact.
• Previous anaphylactic reaction, severe systemic response, or serious hypersensitivity to a prior immunization or a known allergy to synthetic ODNs, aluminum, formaldehyde, benzethonium chloride (phemerol).
• Plan to have an elective surgery at any point during the study until after the final safety phone contact.
• Have donated or plan to donate blood within one month prior to enrollment or at any point during the study until after the final safety phone contact.
• Use of any investigational or non-registered product (drug, vaccine or biologic) within 30 days preceding the dose of study vaccine, or planned use during the study until after the final safety phone contact.
• Planned administration of any commercially-available vaccine from one week prior to the first study vaccination through two weeks after the last vaccination.
• Have experienced chronic dosing (defined as more than 14 days) with any immune-modifying drugs within six months of study enrollment. This includes oral, intramuscular, intra-articular, intravenous, or inhalation corticosteroids except in the case of inhaled or intranasal medications for seasonal allergies.
• Receipt of immunoglobulins and/or any blood products within the three months preceding study enrollment or at any point during the study period until after the final safety visit on Day 51.
• An abnormal electrocardiogram (ECG) at screening interpreted as 'Abnormal, Significant'. Inclusion of participants with 'Abnormal, Insignificant' ECGs will be based on the principal investigator's discretion.
• Have an active malignancy or history of metastatic or hematologic malignancy.
• Have a history of an autoimmune, inflammatory, vasculitic or rheumaticor rheumatic disease including but not limited to systemic lupus erythematosus, Guillain-Barré syndrome, myasthenia gravis, polymyalgia rheumatica, diabetes mellitus type I, rheumatoid arthritis or scleroderma.
• A positive laboratory evidence of hepatitis B, hepatitis C, or human immunodeficiency virus (HIV) HIV-1 or HIV-2 infection.
• Positive result on urine drug screen, any evidence of ongoing drug abuse or dependence (including alcohol), or recent history (over the past five years) of treatment for alcohol or drug abuse.
• Has an acute disease at the time of enrollment.
• Any medical condition that, in the opinion of the investigator, could adversely impact the participant's involvement or the conduct of the study.
• Have a significant chronic condition, e.g., serious cardiovascular, pulmonary, hepatic, type II diabetes mellitus or renal disease that, in the opinion of the investigator, would render treatment unsafe or would interfere with trial evaluations or completion of the study.
• An opinion of the investigator that it would be unwise to allow the participant to be randomized into the study.
• Member or immediate family member of an investigator site team.