Velocity 2: An Anthrax Vaccine and Antibiotics Clinical Study: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Velocity 2: An Anthrax Vaccine and Antibiotics Clinical Study (NCT04067011), a randomized phase 2 study. The primary outcome is Ratio of Ciprofloxacin Area Under the Curve From 0 to 12 Hours (AUC0-12h) and Maximum Concentration (Cmax) on Days 8 and 35.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, open-label, parallel-group study of AV7909 administered with ciprofloxacin or doxycycline, with an AV7909-alone group. The registry record describes three investigational groups allocated in a 1:1:1 ratio. The recorded enrollment was 210. The study population was healthy adults; the condition listed in the record is anthrax.

All three groups received AV7909 according to the study visit schedule. The first group concomitantly received ciprofloxacin, the second received doxycycline, and the third received AV7909 without either listed antibiotic. The study description says that the antibiotics were administered orally before and following intramuscular AV7909 administration. The vaccine schedule consisted of two doses two weeks apart.

The primary endpoint focuses on ciprofloxacin pharmacokinetics in the ciprofloxacin group. It compares measurements taken on Day 8, before AV7909 vaccination, with measurements on Day 35, after vaccination. Blood sampling was scheduled before the ciprofloxacin dose and at multiple post-dose times through 12 hours on each of those days. The endpoint description says that steady-state area under the concentration-time curve and maximum concentration were derived from serum concentrations.

The registry lists a secondary immunogenicity outcome: geometric mean TNA 50% neutralizing factor values two weeks after the second AV7909 vaccination, at Day 37 ± 1 Day. The study start date is 2019-08-12, the primary completion date is 2020-03-05, and the status is completed. Further details about conduct, adherence, withdrawals, or protocol deviations are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The number of analyzed participants represents the number of participants that met pre-specified protocol criteria for inclusion in the PK analysis population.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Intent to treat population: all subjects who were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Ratio of Ciprofloxacin Area Under the Curve From 0 to 12 Hours (AUC0-12h) and Maximum Concentration (Cmax) on Days 8 and 35, measured over Pre-dose and 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, 10 and 12 hours post-ciprofloxacin dose on Days 8 (pre-AV7909 vaccination) and 35 (post-AV7909 vaccination).

The primary endpoint measures the ratio of ciprofloxacin exposure on Day 35 to exposure on Day 8. It includes two pharmacokinetic measures: area under the serum concentration-time curve from 0 to 12 hours (AUC0-12h) and maximum concentration (Cmax). Day 8 is identified as before AV7909 vaccination, and Day 35 as after vaccination. The record describes geometric mean ratios and corresponding 90% confidence intervals.

Pharmacokinetic measures describe drug concentrations over time. AUC represents overall exposure during the stated sampling interval, while Cmax describes the highest measured concentration in that interval. Comparing the post-vaccination and pre-vaccination measurements is intended to assess whether ciprofloxacin exposure differed across those study visits when AV7909 was administered as scheduled. This is a drug-vaccine interaction question, not a direct measure of clinical benefit.

Ratios express the post-vaccination measure relative to the pre-vaccination measure. A ratio at the point of equality would indicate no change in the measured quantity between visits; a ratio on either side would indicate a relative increase or decrease. The confidence interval conveys uncertainty around the estimated ratio. The record does not report the endpoint estimates, interval limits, or a conclusion about whether the measurements differed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is based on geometric mean ratios for two pharmacokinetic measures: AUC0-12h and Cmax. The ratio compares the value on Day 35 with the value on Day 8. Day 8 is the pre-AV7909 vaccination assessment, and Day 35 is the post-vaccination assessment. The registry describes serum concentration measurements taken before the ciprofloxacin dose and at scheduled times through 12 hours after dosing on both days.

Why use pharmacokinetic measures?

As a general statistical and pharmacological explanation, concentration measurements over time provide information about drug exposure and peak concentration. AUC summarizes exposure across the specified sampling window, whereas Cmax focuses on the maximum concentration reached during that window. These measures address different features of the concentration profile, so reporting both can describe the exposure pattern more fully than either alone. Their interpretation remains tied to the drug, sampling schedule, population, and analysis specified for the study.

The study description says that steady-state AUC0-12h and Cmax were derived from serum concentrations. The record does not give further details of the derivation, such as the specific pharmacokinetic estimation procedure or handling of measurements outside the sampling schedule. Those details are not reported in the registry record.

What does a geometric mean ratio express?

As a general explanation, geometric means are used for positive measurements that are analyzed on a multiplicative scale. A ratio of geometric means expresses the relative level of one measurement compared with another, rather than an absolute difference between them. In this endpoint, the comparison is Day 35 relative to Day 8. The equality reference is the ratio that represents the same geometric mean at both visits; a value on one side or the other indicates relative increase or decrease. The actual ratio estimates are not reported in the registry record.

Working on a logarithmic scale is common for ratio analyses because multiplicative differences become additive on that scale. This can make statistical modeling more suitable when measurements are positive and their variation is proportional to their level. That is general context, not a statement about the exact calculation used in this study: the transformation and model are not reported in the registry record.

How should the confidence interval be read?

The registry describes a 90% confidence interval around each mean ratio. As a general explanation, a confidence interval communicates the statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision in the estimate; a wider interval indicates less precision. It does not describe the range of individual participants’ values, and it is not a guarantee about the location of the true value.

For a ratio, the interval is interpreted relative to the equality reference. If an interval is compatible with values on both sides of that reference, it allows for both a relative increase and a relative decrease under the analysis. If an interval lies to one side, it indicates that the estimated relative change is more constrained in that direction. These are general principles; the actual interval limits and any formal interpretation are not reported in the registry record.

A confidence interval’s practical meaning also depends on the analysis population, data quality, and methods used to obtain it. The record says that the analyzed participants were those meeting pre-specified protocol criteria for inclusion in the pharmacokinetic analysis population. It does not state the number analyzed or describe the criteria in detail. The statistical model, any covariate adjustment, and the handling of missing or unusable concentration measurements are not reported in the registry record.

What does the visit comparison establish?

The endpoint compares two assessments in the ciprofloxacin group, before and after vaccination. As a general design consideration, a before-and-after comparison can describe how measurements changed between the specified visits. It does not, by itself, separate the effect of AV7909 from every other possible difference between visits. The parallel groups may support other comparisons, but the registry’s primary endpoint description does not define a contrast of change against either comparison group.

Random allocation applies to assignment among the three groups. It does not make the two measurement days within a participant separate randomized conditions. The record does not report the statistical analysis plan or whether repeated measurements were modeled jointly. Thus, the exact inferential approach cannot be reconstructed from the registry description.

Which participants contribute to the endpoint?

The registry states that the primary pharmacokinetic analysis population includes participants who met pre-specified protocol criteria. This distinction matters because enrollment and analysis population are not necessarily the same: participants may lack usable outcome measurements or fail an analysis criterion. That is a general possibility, not a claim about what occurred in this trial. The count analyzed and the reasons for any exclusions are not reported in the registry record.

Sample-size assumptions are described as a planning illustration based on an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration is not the trial’s own design justification. No resulting planning estimates are reported in the registry record. Such calculations are hypothetical planning quantities, not observed power and not evidence about the precision of the trial’s actual results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists three outcome measures and six analyses, but the statistical plan governing those analyses is not reported in the registry record. In particular, the record does not describe whether the analyses were designated as primary, secondary, or exploratory beyond the outcome labels, or how interpretation was to account for multiple outcomes or comparisons.

As a general statistical consideration, evaluating multiple outcomes or analyses creates more opportunities for apparently notable findings by chance. Methods for addressing this can include prespecifying a hierarchy, adjusting inference, or treating results as exploratory. Which approach, if any, was used in this study is not reported in the registry record. The primary endpoint includes two pharmacokinetic measures, AUC0-12h and Cmax, but the record does not state how their joint interpretation was handled.

The primary endpoint description identifies an analysis population defined by protocol criteria, but the number analyzed and the details of those criteria are not reported in the registry record. Missing-data frequency, reasons for missing measurements, and methods for handling missing or incomplete pharmacokinetic profiles are also not reported in the registry record. The record does not describe imputation, sensitivity analyses, or whether participants with partial concentration profiles contributed to either measure.

The registry record does not report an interim analysis plan, a stopping rule, or a complete statistical analysis plan. It also does not explain whether any deviations from planned analyses occurred. Without these details and the numerical outcome estimates, readers cannot assess the multiplicity strategy or the robustness of results to missing data and analysis-population decisions.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastroenteritis viral (1.6%), uterine prolapse (1.6%).

The registry reports serious adverse events and other adverse events separately for the three groups. In the ciprofloxacin plus AV7909 group, 1 participant was recorded with a serious adverse event and 17 with other adverse events; 0 deaths were recorded. In the doxycycline plus AV7909 group, the corresponding counts were 0, 17, and 0. In the AV7909 group, the counts were 1, 16, and 0. The numbers at risk for these summaries were 62, 64, and 64, respectively.

The listed serious adverse-event terms were Gastroenteritis viral and Uterine prolapse, each reported as 1.6%. These figures describe events recorded during the study; they do not establish that an event was caused by a study intervention. The registry record does not provide detailed event narratives, timing, duration, severity beyond the serious-event classification, or investigator judgments of relatedness.

As a general interpretation point, adverse-event counts are descriptive. Differences in counts across groups should be read with the study context and exposure period in mind, and small counts provide limited information about uncommon risks. The registry record does not report a comparative statistical analysis of these safety counts. They should not be treated as a substitute for the missing pharmacokinetic or immunogenicity results.

12. What the Result Does, and Does Not, Mean

This study addresses a focused drug-vaccine interaction question. Its primary outcome is designed to compare ciprofloxacin exposure before and after AV7909 vaccination, using AUC0-12h and Cmax. Its listed secondary outcome concerns TNA 50% neutralizing factor values after the second vaccination. These endpoints describe pharmacokinetics and immunogenicity, respectively; they are not measures of clinical protection against anthrax.

The registry record identifies the randomized groups, study schedule, endpoint definitions, and selected safety counts. However, the numerical results for the primary pharmacokinetic ratios and their 90% confidence intervals are not reported in the registry record. The secondary immunogenicity results are also not reported in the registry record. Consequently, the record does not allow a reader to determine the size or precision of the measured changes or to compare immunogenicity outcomes among groups.

The design’s random allocation and parallel groups describe how participants were assigned, but the primary endpoint is defined as a Day 35-to-Day 8 comparison in the ciprofloxacin group. The record does not report a primary between-group contrast for that outcome. It is therefore important not to treat the endpoint definition as proof of a treatment effect, or to infer a comparison that the reported analysis does not specify.

The safety information describes event counts in the study groups, including zero recorded deaths. Such observations are informative as a record of events during the study, but they do not alone establish causation or fully characterize risk. The record does not report enough detail to assess all aspects of event attribution or follow-up.

In short, the registry record establishes what the study set out to measure and gives some design and safety information. It does not report the outcome estimates needed to answer whether the measured ciprofloxacin exposure or vaccine immunogenicity changed. No conclusion about clinical effectiveness follows from the information reported.

13. Why This Trial Matters Statistically

The study is statistically notable for separating a drug-exposure question from a vaccine-immunogenicity question. Ciprofloxacin AUC0-12h and Cmax characterize aspects of antibiotic concentration over time, while the listed TNA outcome concerns an immune response measure. These are different types of outcomes and answer different questions; evidence about one would not automatically answer the other.

The primary endpoint’s before-and-after structure also illustrates why the contrast being estimated matters. The endpoint compares ciprofloxacin measurements on Day 35 with those on Day 8 in the ciprofloxacin group. That is not the same as comparing changes across randomized groups. Distinguishing these estimands helps prevent a within-group change from being misread as a randomized treatment contrast.

Geometric mean ratios and confidence intervals are useful statistical summaries when the scientific question concerns relative exposure. The ratio communicates the scale of change, while the interval describes its precision. In this record, however, the estimates and intervals are not reported in the registry record. The design and endpoint definitions therefore cannot substitute for the results required to judge the size and uncertainty of the observed change.

The record also makes the analysis population relevant: only participants meeting protocol criteria were included in the pharmacokinetic analysis population. Reporting its size and exclusions would help readers understand how much of the enrolled group contributed to the endpoint. Those details are not reported in the registry record.

Finally, the study demonstrates the limits of interpreting safety counts without an analysis plan or detailed event context. The counts are useful descriptive information, but they do not answer the primary pharmacokinetic question. A complete statistical interpretation requires endpoint estimates, uncertainty measures, analysis-population details, and a clear account of how outcomes and missing observations were handled.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The main limitation for interpreting the registry record is that it does not report numerical results for the primary endpoint. The AUC0-12h and Cmax ratios and their 90% confidence intervals are not reported in the registry record, so neither the estimated changes nor their precision can be assessed. The listed secondary immunogenicity outcome also lacks numerical results in the registry record.

The primary endpoint is described as a within-group comparison between Day 8 and Day 35. A direct comparison of changes between the ciprofloxacin group and a concurrent group is not described as the primary endpoint. This limits what can be inferred from that endpoint about differences attributable specifically to vaccination rather than other differences between visits.

The registry identifies a protocol-defined pharmacokinetic analysis population but does not report its size or detailed inclusion criteria. The number of participants with complete profiles, the amount and pattern of missing data, and reasons for exclusion are not reported in the registry record. These details matter when evaluating whether the analyzed participants represent the randomized group.

The statistical analysis plan, model specifications, multiplicity strategy, and any sensitivity analyses are not reported in the registry record. Nor does the record provide detailed safety-event context, such as event timing or relatedness. These omissions constrain interpretation of both the outcome estimates and the adverse-event counts.

The study enrolled healthy adults, as described in the record. The results’ applicability to populations beyond that study population is not established by the registry information. The record also does not report how adherence, withdrawals, or protocol deviations were handled.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Velocity 2: An Anthrax Vaccine and Antibiotics Clinical Study — NCT04067011.
• Registry record last updated 2025-09-08; status last verified 2025-08.
• Results first posted 2021-06-30.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

Velocity 2 (NCT04067011) was a completed Phase 2 randomized, open-label, parallel-group study with an enrollment of 210. It evaluated AV7909 with ciprofloxacin, AV7909 with doxycycline, and AV7909 alone in healthy adults. The study started on 2019-08-12 and reached primary completion on 2020-03-05.

The primary outcome was the geometric mean ratio for ciprofloxacin AUC0-12h and Cmax on Day 35 relative to Day 8, with a 90% confidence interval. The registry record does not report the numerical primary results. A secondary outcome was the geometric mean TNA 50% neutralizing factor two weeks after the second vaccination, at Day 37 ± 1 Day; its numerical result is not reported in the registry record.

The record includes group-level serious and other adverse-event counts and reports zero deaths in each group. It does not report the statistical analysis plan, primary outcome estimates, or detailed missing-data handling.