A Phase 2 Drug-Vaccine Interaction Study of AV7909 and Ciprofloxacin or Doxycycline on Antibiotic Pharmacokinetics

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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 (NF50) values generated by a toxin neutralizing antibody (TNA) assay. Steady-state maximum concentration, Cmax and area under the curve from 0 to 12 hours, AUC0-12hrs 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 AUC0-12h [90% CI: 0.89, 1.07] and Cmax [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 AUC0-12h [90% CI: 0.82, 1.03] was within the equivalence criteria, but LB of 90% CI for Cmax (0.79) was below the equivalence criteria [0.80, 1.25]. This result for steady-state DOX Cmax 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 NF50 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