Effect of Co-administration of the anthrax vaccine adsorbed, adjuvanted with ciprofloxacin or doxycycline on antibiotic pharmacokinetics and the vaccine immunogenicity: A phase 2 drug-vaccine interaction study.

BACKGROUND

CYFENDUS® vaccine (Anthrax Vaccine Adsorbed, Adjuvanted) with the recommended antibacterial drugs is licensed for post-exposure prophylaxis (PEP) following suspected or confirmed Bacillus anthracis exposure. This pre-licensure study examined potential interaction of CYFENDUS vaccine with ciprofloxacin and doxycycline when administered concomitantly.

METHODS

In this Phase 2, open-label study, healthy adult participants (18 to 45 years of age; n = 210) were randomized to receive either ciprofloxacin+CYFENDUS vaccine, doxycycline+CYFENDUS vaccine, or CYFENDUS vaccine only. Pharmacokinetic (PK) parameters of antibacterials such as steady-state maximum concentration (Cmax) and area under the curve from 0 to 12 h (AUC0-12h) were assessed. Immunogenicity of the vaccine was evaluated using 50 % neutralizing factor (NF50) values generated by toxin neutralizing antibody (TNA) assay. Solicited reactogenicity and adverse events (AEs) were collected for safety evaluation.

RESULTS

The PK endpoint was met for ciprofloxacin. The vaccine had no effect on PK with 90 % confidence intervals (CIs) of the mean ratios for AUC0-12h [90 % CI: 0.8895,1.0718] and Cmax [90 % CI: 0.8693,1.0838] contained within the predefined equivalence criteria [0.80, 1.25]. The PK endpoint was not met for doxycycline, wherein the 90 % of the mean ratios for AUC0-12h [90 % CI: 0.8187,1.0278] was within the equivalence criteria, but the lower bound of the 90 % CI for Cmax [90 % CI: 0.7841,1.0271] was below the equivalence limits [0.80, 1.25]; this impact on Cmax may be negligible to the extent that doxycycline efficacy is correlated with AUC. The immunogenicity endpoint was met, wherein the lower bound 95 % CIs for geometric mean ratio of TNA NF50 for the vaccine with ciprofloxacin (0.78) or doxycycline (0.81) to vaccine alone were above the non-inferiority margin (0.5). Most solicited reactogenicities and AEs were Grade 1 or 2 in severity.

CONCLUSIONS

CYFENDUS vaccination with or without ciprofloxacin or doxycycline had an acceptable safety profile and co-administration did not affect the relevant PK and immunogenicity parameters.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04067011.