Compatible co-administration of BioThrax® vaccine and ciprofloxacin-Results of a randomized open-label drug-vaccine interaction trial

David Cassie; Janice Longstreth; Robert Hopkins; Ericka Hunter-Stitt; Bojan Drobic; Melisa Bellani

doi:10.1016/j.jvacx.2024.100431

Compatible co-administration of BioThrax® vaccine and ciprofloxacin-Results of a randomized open-label drug-vaccine interaction trial

Vaccine X. 2024 Jan 7:17:100431. doi: 10.1016/j.jvacx.2024.100431. eCollection 2024 Mar.

Authors

David Cassie¹, Janice Longstreth², Robert Hopkins³, Ericka Hunter-Stitt⁴, Bojan Drobic¹, Melisa Bellani¹

Affiliations

¹ Emergent BioSolutions Canada Inc., 155 Innovation Drive, Winnipeg, MB R3T 5Y3, Canada.
² The Institute for Global Risk Research, LLC, 9119 Kirkdale Road, Suite 200, Bethesda, MD 20817, USA.
³ Adaptive Phage Therapeutics, 708 Quince Drive, Gaithersburg, MD 20878, USA.
⁴ Emergent BioSolutions Inc., 400 Professional Drive, Gaithersburg, MD 20879, USA.

Abstract

The recommended treatment for post-exposure prophylaxis (PEP) following known/suspected exposure to Bacillus anthracis involves immunization with anthrax vaccine adsorbed (AVA, i.e., BioThrax® vaccine) and a course of antimicrobial therapy. A drug-vaccine interaction clinical trial was conducted to determine whether this combined treatment might modify antimicrobial exposure or vaccine immunogenicity. A Phase 2, randomized, open-label, multi-center trial involving 154 healthy adult participants was completed to evaluate the effect of AVA immunization (three doses administered subcutaneously (SC) at weeks 0, 2 and 4) on the pharmacokinetics (PK) of ciprofloxacin, as well as the effect of ciprofloxacin administration (500 mg po bid) on the immunogenicity of AVA. PK parameters were derived using noncompartmental analysis of ciprofloxacin serum concentrations. Immunogenicity was assessed using a toxin neutralizing antibody (TNA) assay resulting in 50 % neutralization factor (NF₅₀) values. Safety was assessed via reports of adverse events (AEs), clinically significant changes in laboratory parameters and vital signs, and collection of solicited local and systemic reactogenicity reactions. Statistical analyses of the steady state (SS) and single dose PK parameters C_max and AUC_0--12h indicated that the AVA PEP regimen did not significantly modify ciprofloxacin exposure. Comparison of the geometric mean TNA NF₅₀ values between participants receiving AVA + ciprofloxacin and those receiving AVA alone showed that the combined treatment was non-inferior to AVA alone. The trial met all prospectively defined success criteria for the primary PK endpoint and for the secondary PK and immunogenicity endpoints. There were no deaths, SAEs or AEs leading to drug discontinuation or study withdrawal during the trial. Overall, concomitant administration of ciprofloxacin and AVA produced no significant changes in the PK profile of ciprofloxacin nor in the immunogenicity of AVA. Furthermore, this trial demonstrated that the co-administration of ciprofloxacin and AVA was well tolerated in healthy adult participants.

Keywords: Anthrax; BioThrax®; Drug-vaccine interaction, ciprofloxacin; Post-exposure prophylaxis; Vaccine.