Anthrax
Conditions
Keywords
post-exposure prophylaxis, toxin neutralization assay
Brief summary
The purpose of this clinical trial is to determine whether there is any effect on the antibiotic, ciprofloxacin when taken before and after administration of a 3-dose series of BioThrax® (Anthrax Vaccine Adsorbed or AVA). This study will be conducted in the United States (US) in 154 healthy male and female volunteer subjects ages 18 to 45. The duration of study participation for each subject will be approximately 76 days (approximately 2.5 months)
Detailed description
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.
Interventions
BIOLOGICALBioThrax
route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule
DRUGCiprofloxacin
500 mg twice a day (Days 1-6, 19-21, 33-35, 40-48).
Sponsors
Department of Health and Human Services
Emergent BioSolutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were enrolled from 14 Dec 2012 to 04 Aug 2013 at 3 US sites.
Participants by arm
| Arm | Count |
|---|---|
| BioThrax + Ciprofloxacin PK BioThrax: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule
Ciprofloxacin: 500 mg twice a day | 44 |
| BioThrax + Ciprofloxacin no PK BioThrax: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule
Ciprofloxacin: 500 mg twice a day | 40 |
| BioThrax Only BioThrax: route of administration/schedule- 0.5 mL subcutaneous (SC) injection / 0-2-4 week schedule | 70 |
| Total | 154 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Lost to Follow-up | 3 | 6 | 8 |
| Overall Study | Subject non-compliant | 3 | 3 | 0 |
| Overall Study | Used excluded drug | 0 | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 5 | 6 |
Baseline characteristics
| Characteristic | BioThrax + Ciprofloxacin PK | BioThrax + Ciprofloxacin no PK | BioThrax Only | Total |
|---|---|---|---|---|
| Age, Continuous | 30.5 years STANDARD_DEVIATION 8.76 | 30.8 years STANDARD_DEVIATION 8.05 | 30.2 years STANDARD_DEVIATION 7.29 | 30.4 years STANDARD_DEVIATION 7.88 |
| Age, Customized 18 - 30 years | 22 participants | 20 participants | 35 participants | 77 participants |
| Age, Customized 31 - 45 years | 22 participants | 20 participants | 35 participants | 77 participants |
| Race/Ethnicity, Customized American Indian or Alaskan Native | 0 participants | 1 participants | 2 participants | 3 participants |
| Race/Ethnicity, Customized Asian | 0 participants | 2 participants | 1 participants | 3 participants |
| Race/Ethnicity, Customized Black or African America | 20 participants | 14 participants | 34 participants | 68 participants |
| Race/Ethnicity, Customized Multiple | 0 participants | 1 participants | 0 participants | 1 participants |
| Race/Ethnicity, Customized White | 24 participants | 22 participants | 33 participants | 79 participants |
| Sex: Female, Male Female | 20 Participants | 20 Participants | 36 Participants | 76 Participants |
| Sex: Female, Male Male | 24 Participants | 20 Participants | 34 Participants | 78 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 6 / 38 | 7 / 39 | 14 / 67 |
| serious Total, serious adverse events | 0 / 38 | 0 / 39 | 0 / 67 |
Outcome results
Primary
Ratios of Ciprofloxacin Area Under the Curve and Cmax (Day 5/Day 44)
Ratios of Area Under the Curve from zero to 12 hours (AUC0-12h) and maximum concentration (Cmax) achieved for ciprofloxacin (Day 5/Day 44).
Time frame: Day 5 and Day 44 in Arm 1
Population: Per protocol population: all subjects in arm 1 who received any dose of ciprofloxacin, had adequate PK data on Day 5 and Day 44, had received all three BioThrax doses, and who had no key protocol deviations (e.g., insufficient blood sample) that would be expected to affect the ciprofloxacin PK assessment.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Arm 1 = BioThrax (0.5 mL) + Ciprofloxacin (500 mg Bid) + PK | Ratios of Ciprofloxacin Area Under the Curve and Cmax (Day 5/Day 44) | Ratio Cmax Day 44/Day 5 | 0.944 ratio |
| Arm 1 = BioThrax (0.5 mL) + Ciprofloxacin (500 mg Bid) + PK | Ratios of Ciprofloxacin Area Under the Curve and Cmax (Day 5/Day 44) | Ratio AUC0-12hr Day 44/Day 5 | 0.887 ratio |
Comparison: Analysis of Ciprofloxacin Area Under the Curve at Day 5 and Day 44.90% CI: [0.831, 0.948]
Comparison: Analysis of Cmax at Day 5 and Day 4490% CI: [0.852, 1.046]
Secondary
Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) Levels
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.
Time frame: Two weeks after last vaccination
Population: BioThrax immunogenicity population: received 3 vaccinations and had samples taken within the study-specified windows; had a valid immunogenicity result within 2 wks of the last vaccination; had no evidence of previous anthrax vaccination and received the correct BioThrax dose at all 3 times; received vaccine maintained at the proper temperature.
| Arm | Measure | Value (GEOMETRIC_MEAN) |
|---|---|---|
| Arm 1 = BioThrax (0.5 mL) + Ciprofloxacin (500 mg Bid) + PK | Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) Levels | 1.170 titer |
| BioThrax Only (Arm 3) | Geometric Mean Titer (GMT) of Toxin Neutralizing Antibody (TNA) Levels | 0.923 titer |
95% CI: [0.898, 1.787]