Ciprofloxacin BioThrax Co-Administration Study

BioThrax is the only FDA-licensed vaccine for the prevention of anthrax infection. This is a randomized, open-label, Phase 2, multi-center trial to investigate the potential interactions of ciprofloxacin and BioThrax.

• BioThrax (Biological), also known as Anthrax Vaccine Adsorbed, AVA: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule
• Ciprofloxacin (Drug): 500 mg twice a day (Days 1-6, 19-21, 33-35, 40-48).

Primary outcomes

• Ratios of Ciprofloxacin Area Under the Curve and Cmax (Day 5/Day 44) [Day 5 and Day 44 in Arm 1]: Ratios of Area Under the Curve from zero to 12 hours (AUC0-12h) and maximum concentration (Cmax) achieved for ciprofloxacin (Day 5/Day 44).

Secondary outcomes

• Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) Levels [Two weeks after last vaccination]: Blood was collected in arms 1 and 2 at day 48 ( 2 weeks following last vaccination) and in arm 3 at day 43 ( 2 weeks following last vaccination) for TNA assay to determine the NF50 antibody titer for calculating GMT.

Sex: All, ages: 18 Years to 45 Years, accepts healthy volunteers

Inclusion Criteria:

* Be between 18 and 45 years of age, at the time of enrollment
* Be in good health as determined by the investigator from medical history and a physical examination.
* If a pre-menopausal female, must be using acceptable methods of birth control.
* Be willing and able to return for all follow-up visits and blood and urine collections for the duration of the trial
* Be willing and able to complete a web-enabled electronic diary and report concomitant medications, adverse events, and BioThrax reactogenicity events during the trial
* Be able to understand and communicate in English.

Exclusion Criteria:

* Prior immunization with anthrax vaccine or known exposure to anthrax organisms
* Intend to enlist in the military during the study.
* Have a known allergy to aluminum hydroxide, formaldehyde, benzethonium chloride, or latex.
* Plan to receive experimental products 30 days prior to study entry or at any time during the study
* Have received a live vaccine in the 30 days before study entry
* Plan to receive a live vaccine at any time during the study.
* Have ongoing drug abuse/dependence (including alcohol) issues and/or test positive in a urine drug screen for amphetamines, barbiturates, cocaine or opiates
* Have received immunosuppressive therapy (including systemic steroids) within 30 days prior to trial entry
* Have any other condition known to produce or be associated with immunosuppression
* Have received cytotoxic therapy in the previous 5 years
* A chronic condition that, in the opinion of the Investigator, would render vaccination unsafe or would interfere with trial evaluations or completion of the study.

Participant flow

Outcome results

• Ratios of Ciprofloxacin Area Under the Curve and Cmax (Day 5/Day 44) (Primary), Mean, ratio: Arm 1 = BioThrax (0.5 mL) + Ciprofloxacin (500 mg Bid) + PK 0.944 (0.852 to 1.046)
• Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) Levels (Secondary), Geometric mean, titer: BioThrax + Ciprofloxacin (Arms 1 + 2) 1.170 (0.912 to 1.500); BioThrax Only (Arm 3) 0.923 (0.723 to 1.780)

Adverse events

Time frame: Arm 1: enrollment, Days 0-5, 20, 34, 39-44, 48, or the early withdrawal visit (EWV) for a max of 16 visits. Arm 2: enrollment, Days 1, 5, 20, 34, 48, or EWV for a max of 6 visits. Arm 3: enrollment, Days 1, 15, 29, 43, or EWV for a max of 5 visits.

Other adverse events by term

• Results publication: Cassie D, Longstreth J, Hopkins R, Hunter-Stitt E, Drobic B, Bellani M. Compatible co-administration of BioThrax(R) 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. PMID 38352727

• Robert Hopkins, MD, MPH, TM, Principal investigator, Emergent BioSolutions Inc.