Vaccine · 2025
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.
СтатьяКлиническое исследование II фазыРандомизированное исследованиеНазвание и аннотация: Перевод в очереди
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Drobic Bojan, Akintunde Gideon, Kim Julia, Mirceta Mila, Beach Marinda, Komlenovic Vanja
Аннотация
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.
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.