Abstract
BACKGROUND: AV7909 (Anthrax Vaccine Adsorbed, Adjuvanted) vaccine was developed for post-exposure prophylaxis (PEP) of disease following suspected or confirmed exposure to Bacillus anthracis administered in conjunction with recommended antibacterial regimen. A drug-vaccine interaction study (NCT04067011) was conducted to examine whether co-administration of AV7909 with ciprofloxacin (CIP) or doxycycline (DOX) affects antibiotic pharmacokinetics (PK) or AV7909 immunogenicity in healthy adults. METHODS: A Phase 2, randomized, open-label study was conducted to assess the effects of AV7909 (intramuscularly (IM) at 0, 2 weeks) on PK profiles of orally administered CIP and DOX in healthy adults between 18 and 45 years of age. Participants (n=210) were randomized to receive AV7909+CIP, AV7909+DOX or AV7909 alone. Serum concentrations of CIP and DOX were determined using liquid chromatography with tandem mass spectrometry, while AV7909 immunogenicity was evaluated using 50% neutralizing factor (NF(50)) values generated by a toxin neutralizing antibody (TNA) assay. Steady-state maximum concentration, C(max) and area under the curve from 0 to 12 hours, AUC(0-12hrs) for CIP and DOX were calculated. Safety was evaluated by collection of solicited reactogenicity and reports of adverse events (AEs). RESULTS: Primary PK endpoint for CIP was met, wherein 90% confidence intervals (CIs) of mean ratios for steady-state AUC(0-12h) [90% CI: 0.89, 1.07] and C(max) [90% CI: 0.87, 1.08] were contained within the equivalence criteria [0.80, 1.25]. The endpoint was marginally missed for DOX, wherein lower bound (LB) of 90% CI for AUC(0-12h) [90% CI: 0.82, 1.03] was within the equivalence criteria, but LB of 90% CI for C(max) (0.79) was below the equivalence criteria [0.80, 1.25]. This result for steady-state DOX C(max) is likely limited given that its efficacy is mainly AUC-driven. The immunogenicity endpoint was met, wherein LB of two-sided 95% CI of the geometric mean ratio of TNA NF(50) was >0.5 (0.78 for CIP, 0.81 for DOX). The majority of solicited reactogenicities and AEs were Grade 1 or 2 in severity. CONCLUSION: Co-administration of CIP or DOX with AV7909 did not alter the relevant PK parameters of antibacterials or immunogenicity of AV7909 and was well tolerated in healthy adults. DISCLOSURES: Gideon Akintunde, Director Clinical Development, Emergent Biosolutions: Employee Bojan Drobic, Director Clinical Development, Emergent Biosolutions: Employee Lisa Bedell, Director Biostatistic, Emergent Biosolutions: Employee Lu Gan, Director Biostatistic, Emergent Biosolutions: Employee Julia Kim, Scientist Clinical Development, Emergent Biosolutions: Employee Marinda Beah, Manager Clinical Trials Development, Emergent Biosolutions: Employee Isaac Ghinai, Medical Director, Emergent Biosolutions: Employee Santiago Barona Collado, Medical Director, Emergent Biosolutions: Employee