Phase 3 trial evaluating the immunogenicity and safety of a three-dose BioThrax® regimen for post-exposure prophylaxis in healthy adults

Abstract

Background: This study was conducted to support licensure of a post-exposure prophylaxis indication for BioThrax(®) (anthrax vaccine adsorbed) concurrent with antimicrobials for individuals exposed to aerosolized anthrax spores.

Methods: The immunogenicity and safety of a three-dose regimen (0, 2, and 4 weeks) of BioThrax administered subcutaneously (SC) were evaluated in 200 healthy adults 18-65 years of age. Toxin-neutralizing antibody (TNA) was expressed as 50% neutralization factor (NF50) at predetermined time points through Day 100. Safety was assessed by physical examinations, vital signs, solicited local and systemic reactions using web-enabled subject diaries, in-clinic solicited reactions, and unsolicited adverse events (AEs).

Results: The prospectively defined success criteria for the primary and secondary endpoints were met. This required the lower bound of the 95% confidence interval (CI) for the proportion of subjects with a TNA NF50 value to be greater than 40% at Day 63 (primary), Day 70 (secondary) and Days 63-100 (secondary). At Day 63, 71% of subjects achieved a TNA NF50 threshold value ≥ 0.56, with a lower bound of the 95% CI ≥ 40% (64%). The percentage of subjects achieving a TNA NF50 threshold value ≥ 0.56 at Day 70 was 58% (95% CI: 50%, 65%), and the mean value on Days 63-100 (inclusive) was 53% (95% CI: 41%, 55%). The threshold TNA NF50 value of 0.56 was developed from previous rabbit challenge and human immunogenicity studies. No related serious AEs occurred during the study, and no subjects withdrew from the study because of an AE. Tenderness and pain at the injection site were recorded most often in subject diaries following vaccination.

Conclusions: BioThrax, administered as three SC doses at 0, 2, and 4 weeks, was well tolerated. The prospectively defined success criteria for TNA levels on Days 63, 70, and 63-100 were achieved.

Keywords: Anthrax; BioThrax(®); Clinical trial; Immunogenicity; Post-exposure prophylaxis; Vaccine.