This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid (NCT01701999), a na phase 2 study. The primary outcome is Four-Fold Increase in Neutralizing Antibody Concentration (NAC).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01701999 |
| Phase | Phase 2 |
| Condition | Botulism |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | California Department of Public Health |
| Results posted | Yes |
2. Clinical Question
Population
Volunteers previously immunized with pentavalent botulinum toxoid for occupational protection. The study description characterizes participants as healthy and considers those with neutralizing antibody titers as potential plasma donors for BabyBIG® production. The registry does not give further eligibility details or a more specific description of the analyzed population.
Intervention
A single dose of recombinant botulinum vaccine A/B (rBV A/B). The official title specifies a 40-µg dose. The intervention is a biological product.
Comparator
There was no control group or randomized comparison. The study is described as open-label, uncontrolled, and single-group. Its two parts are described as different study stages, not as treatment and control arms.
Primary question
What proportion of participants achieved a four-fold or greater increase in neutralizing antibody concentration from Week 0 to Week 4 for botulinum toxin A and toxin B? The registry description states that a proportion of at least 0.50 was considered a success. The observed proportion and whether that criterion was met are not reported in the registry record.
The question is about antibody response after vaccination in people who had already received pentavalent botulinum toxoid, rather than about a comparison between vaccine and placebo or another treatment. The stated purpose was to evaluate safety, tolerability, and immunogenicity, including neutralizing antibody levels for toxin types A and B. The registry also lists secondary outcomes involving a three-fold increase in neutralizing antibody concentration and a two-fold increase in the area under the neutralizing antibody concentration curve. The reported endpoint description does not establish whether participants had to meet the four-fold criterion for both toxin types simultaneously or how results for the two types were combined; that rule is not reported in the registry record.
3. Trial Design
This was a Phase 2b, two-part, open-label, uncontrolled study. Its model is single-group, with no random allocation and no masking. The study evaluated a single dose of recombinant botulinum vaccine A/B in volunteers previously immunized with pentavalent botulinum toxoid. The official title specifies a 40-µg dose. The registry lists 45 participants as enrolled.
The two parts had different stated purposes. Part 1 is titled Initial Safety and Immunogenicity and includes 8 participants at risk for the reported adverse-event summaries. Part 2 is titled Safety, Immunogenicity, and Plasma Collection and includes 37 participants at risk for those summaries. These labels describe study stages; they do not make the parts randomized or like-for-like comparison groups. The registry does not report additional details about how participants entered each part or whether procedures differed between parts.
The study started in 2013-02, reached primary completion in 2015-06, and has completed status. The sponsor is the California Department of Public Health. Botulism is the listed condition. The intervention is rBV A/B.
Because there was no concurrent control group, the design can describe outcomes observed after vaccination in this study population, but it cannot estimate a randomized between-group treatment contrast. Open-label status means masking was not used; the registry does not report further details about outcome assessment. Protocol details beyond the listed design, including the rationale for the two-part structure and the planned statistical methods, 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
| Stage | Initial Safety and Immunogenicity (Part 1) | Safety, Immunogenicity, and Plasma Collection (Part 2) |
|---|---|---|
| STARTED | 8 | 37 |
| COMPLETED | 8 | 37 |
| NOT COMPLETED | 0 | 0 |
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.
| Characteristic | Unit | Initial Safety and Immunogenicity (Part 1) | Safety, Immunogenicity, and Plasma Collection (Part 2) | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 37 | 45 | |
| Age, Continuous | years | 50.3 (SD 13.5) | 44.0 (SD 10.7) | 45.1 (SD 11.3) |
| Sex: Female, Male: Female | Participants | 3 | 20 | 23 |
| Sex: Female, Male: Male | Participants | 5 | 17 | 22 |
6. Primary Endpoint
The registry lists the primary outcome as Four-Fold Increase in Neutralizing Antibody Concentration (NAC), measured over Week 0 to Week 4.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | proportion of participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is the proportion of participants with a four-fold or greater increase in neutralizing antibody concentration (NAC) from Week 0 to Week 4. The registry describes the outcome for botulinum toxin A and toxin B and states that a proportion of at least 0.50 was considered a success. The endpoint is binary at the participant level: a person either meets the specified increase criterion or does not, according to the study’s endpoint definition. The exact rule for combining the toxin A and toxin B measurements into a participant-level outcome is not reported in the registry record.
Neutralizing antibody concentration is used as an immunogenicity measure: it records an antibody response capable of neutralizing the toxin in the stated assay context. Comparing Week 4 with Week 0 focuses the endpoint on change after vaccination relative to the participant’s starting measurement. The registry’s stated success threshold gives a benchmark for judging the proportion, but it does not substitute for the observed result or its precision.
The primary endpoint result, including the number or proportion meeting the criterion and any confidence interval, is not reported in the registry record. Therefore, the endpoint definition can be described, but the posted registry information does not establish how many participants achieved the response or whether the stated success benchmark was reached.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record identifies a primary immunogenicity question and a threshold for considering the response proportion a success, but it does not report the observed primary endpoint result. There is consequently no posted proportion, participant count, or confidence interval with which to assess the size or precision of the response. The threshold of at least 0.50 is a criterion stated in the endpoint description, not evidence that the study met it.
The study enrolled 45 participants and used a single-group, open-label, uncontrolled design. Its two parts had 8 and 37 participants at risk in the adverse-event summaries, respectively. Those stages should not be interpreted as a controlled comparison: allocation is listed as not applicable, and no randomized comparator is described. Differences between the parts, if any, could not be isolated as treatment effects from the registry information.
The primary endpoint concerns change in neutralizing antibody concentration between Week 0 and Week 4. A four-fold increase is a threshold-based response measure, not a direct summary of every participant’s antibody concentration or of the distribution of individual changes. The registry also lists secondary outcomes for three-fold increases and for a two-fold increase in the area under the NAC curve, but gives no results for them in the information.
For safety, the registry lists zero serious adverse events in each part. It also lists other adverse events affecting 8 of 8 participants in Part 1 and 34 of 37 in Part 2. These are descriptive counts. With no comparator and no details about event types, severity, timing, or attribution in the listed summaries, they do not establish whether an event was caused by the intervention or how event risks compare with another group. Death counts are not reported in the registry record.
In general, an estimate of a proportion is more informative when accompanied by a confidence interval, because the interval communicates uncertainty around the estimate. Neither the primary proportion nor its interval is reported in the registry record. The posted information therefore supports description of the study design, endpoint definition, and selected adverse-event counts, but not a numerical conclusion about the primary antibody response or a comparative treatment effect.
9. Statistical Methods Explained
The statistical information in the registry supports a limited description of what the study set out to measure, but not a reconstruction of its complete analysis plan. The study is identified as Phase 2b, open-label, uncontrolled, and single-group. No randomized allocation or masking is listed. The primary endpoint is a proportion, and the endpoint description gives its measurement window and response threshold. Details such as the planned estimator, confidence interval method, hypothesis test, or treatment of missing measurements are not reported in the registry record.
What does a proportion endpoint represent?
For a binary endpoint, each participant is classified according to whether a defined event or response occurred. The proportion is the number meeting that definition relative to the relevant participant group. In this study, the specified event is a four-fold or greater increase in NAC between Week 0 and Week 4 for botulinum toxin A and toxin B. The registry says that a proportion of at least 0.50 was considered a success. The number meeting the response definition, the denominator used for the primary endpoint, and the resulting proportion are not reported in the registry record.
As a general statistical concept, a confidence interval around a proportion describes a range of values compatible with the observed data under the chosen method. It helps readers distinguish an estimate from its precision. A point estimate alone would not show how much uncertainty is associated with it, and a threshold-based success criterion does not remove that uncertainty. No primary endpoint confidence interval or method for calculating one is reported in the registry record.
How should the two toxin measurements be understood?
The endpoint description refers to both toxin A and toxin B. It does not specify the participant-level rule for combining the measurements, such as whether the response criterion had to be met for each toxin or whether the outcomes were evaluated separately. That detail matters because different definitions can produce different binary classifications. The registry also names secondary antibody outcomes: a three-fold increase in NAC and a two-fold increase in the area under the NAC curve. Their detailed analysis definitions and results are not reported in the registry record.
What can an uncontrolled design estimate?
In general, a single-group study can describe outcomes observed in its participants after an intervention. Without a concurrent control group, it does not directly estimate how those outcomes would differ under another treatment or under no intervention. This distinction is especially important when interpreting changes from a baseline measurement: the change is observed over time, but the design alone cannot attribute every change to the intervention. Here, the record specifies an uncontrolled, single-group design, so a randomized comparative effect is not available.
What do the planning illustrations mean?
The registry’s planning assumptions describe illustrations computed from the observed effect, not the trial’s own design. They specify a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. Those assumptions do not match the listed single-group study structure, and the illustrations should not be read as the study’s prespecified sample-size justification. The registry explicitly characterizes them as planning illustrations, not the trial’s design. No numerical planning results are stated in the record information. In general, sample-size illustrations address how many participants might be needed under stated assumptions; they are not observed power and do not add evidence about the trial’s actual endpoint result.
Why does over-dispersion matter in general?
For outcomes that count events, over-dispersion means that observed variability exceeds what a simple model assumes. If present, methods that fail to account for it can misstate uncertainty. This is a general statistical consideration, not a feature established for this study: the primary endpoint is a proportion, and the registry does not report an over-dispersion assessment or a count-based primary analysis.
Overall, the registry record describes the endpoint and high-level design but does not report the primary estimate, its uncertainty, the analysis method, or detailed rules for handling participants without complete measurements. Those omissions limit independent statistical interpretation of the immunogenicity result.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary endpoint and two secondary outcome names: a three-fold increase in neutralizing antibody concentration and a two-fold increase in the area under the NAC curve. It also reports four outcome measures and zero analyses in the registry record. The number of listed outcome measures does not establish how many statistical tests were conducted, and the absence of listed analyses does not reveal what analyses may have been performed outside the registry results. A multiplicity strategy, including whether any adjustment for multiple outcomes or tests was planned, is not reported in the registry record.
Multiplicity is a general statistical concern when several outcomes or comparisons are assessed: interpreting many tests without a stated strategy can make isolated findings harder to evaluate. The posted information does not give test results for the primary or secondary outcomes, so there is no basis to assess a pattern across outcomes or the effect of any adjustment.
The primary population field is blank, and the registry does not report detailed analysis-population definitions. It is not stated whether the primary endpoint used all enrolled participants, only those with measurements at both Week 0 and Week 4, or another population. Rules for missing antibody measurements, withdrawals, or participants who did not complete follow-up are not reported in the registry record. The endpoint is defined over Week 0 to Week 4, but the number with complete measurements at both time points is also not reported.
These details matter because the denominator and handling of incomplete observations can affect a proportion estimate. The record does not permit reconstruction of the primary endpoint analysis or evaluation of whether missing data could have influenced it.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Initial Safety and Immunogenicity (Part 1) | 0 | 8 | 0.0% |
| Safety, Immunogenicity, and Plasma Collection (Part 2) | 0 | 37 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Initial Safety and Immunogenicity (Part 1) | 8 of 8 |
| Safety, Immunogenicity, and Plasma Collection (Part 2) | 34 of 37 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Initial Safety and Immunogenicity (Part 1) | Safety, Immunogenicity, and Plasma Collection (Part 2) |
|---|---|---|---|
| Injection site erythema* | General disorders | 5 of 8 | 19 of 37 |
| Injection site pain* | General disorders | 6 of 8 | 15 of 37 |
| Injection site swelling* | General disorders | 3 of 8 | 18 of 37 |
| Procedural complication* | Injury, poisoning and procedural complications | 0 of 8 | 14 of 37 |
| Injection site pruritus* | General disorders | 3 of 8 | 9 of 37 |
| Malaise* | General disorders | 0 of 8 | 5 of 37 |
| Haematocrit decreased | Investigations | 0 of 8 | 5 of 37 |
| Headache* | Nervous system disorders | 0 of 8 | 5 of 37 |
| Erythema* | Skin and subcutaneous tissue disorders | 0 of 8 | 4 of 37 |
| Diarrhoea | Gastrointestinal disorders | 1 of 8 | 2 of 37 |
The adverse-event summary lists zero serious adverse events among the 8 participants at risk in Part 1 and zero among the 37 participants at risk in Part 2. It separately lists other adverse events affecting 8 of 8 participants in Part 1 and 34 of 37 participants in Part 2. These are counts of participants affected, as indicated by the event-summary format; they are not a comparison of randomized groups.
The registry gives no serious adverse event terms in the listed top serious terms. Death counts are not reported in the registry record; a blank or null death entry should not be read as a reported zero. The summaries do not identify the types of other adverse events, their severity, timing, duration, relationship to vaccination, or whether one participant could contribute more than one event. Further event-level detail is not reported in the registry record.
In general, a count of participants with an event is descriptive and does not establish causation. An uncontrolled study also lacks a concurrent comparator for interpreting whether observed events occurred more or less often than they would under another condition. The serious and other-event counts should therefore be read as the registry’s reported safety summaries, with the scope and missing details in mind.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a Phase 2b study evaluated a single dose of rBV A/B in volunteers previously immunized with pentavalent botulinum toxoid. It defines a primary antibody-response endpoint from Week 0 to Week 4 and states that a proportion of at least 0.50 was considered a success. The record does not report the observed primary endpoint result, so it does not show whether that criterion was reached.
The endpoint is an immunogenicity measure: it concerns a specified change in neutralizing antibody concentration. It is not, by itself, a reported measure of clinical outcomes. The registry description explains that volunteers with neutralizing antibody titers would be candidates for plasma donation for BabyBIG® production, but it does not report a clinical outcome or a result establishing the effect of vaccination on such outcomes.
The study’s uncontrolled, single-group design means that outcomes after vaccination are not contrasted with outcomes in a randomized control group. It can describe what was recorded among participants, but it cannot provide a randomized estimate of a difference between intervention and control. The listed adverse-event counts likewise describe participants in the study and do not establish causation.
Zero serious adverse events are listed for both study parts, while other adverse events affected 8 of 8 participants in Part 1 and 34 of 37 in Part 2. The registry does not provide the event-level details needed to characterize those other events, and death counts are not reported in the registry record.
In general, interpretation of a study result depends on both the estimate and its precision, as well as the design and outcome definitions. Here, the key primary estimate and its uncertainty are absent from the registry information. The available record therefore describes the intended question and selected safety summaries, but does not support a conclusion about the magnitude or precision of the primary antibody response.
13. Why This Trial Matters Statistically
This study raises a useful statistical distinction between measuring a biological response and demonstrating a comparative effect. The primary endpoint is a threshold-based proportion of participants with a four-fold or greater increase in NAC over a defined period. Such an endpoint turns a continuous antibody measurement into a response classification. This can make a result easier to compare with a stated criterion, but interpretation depends on the exact response rule, the denominator, and the uncertainty around the proportion.
The registry specifies a success threshold of at least 0.50 but does not report the observed proportion or a confidence interval. Without those values, the threshold cannot be evaluated against the study’s result. Nor can readers judge precision from the enrollment figure alone; precision depends on the endpoint data and analysis, which are not reported in the registry record.
The study also illustrates why design labels matter. Although the two parts have separate safety and immunogenicity descriptions, the study is single-group and uncontrolled. Those parts are not randomized comparison arms. Statistical methods cannot create a concurrent control comparison that the design did not include.
Finally, the registry’s planning assumptions describe an illustration with equal allocation between two arms, while the trial is listed as a single-group study. The record labels the illustration as distinct from the trial’s own design. Keeping planning exercises separate from observed results and prespecified trial methods is important for avoiding claims that the study was designed or powered in a particular way when that information is not reported.
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.
Several limitations specific to this study constrain interpretation of the registry information. First, the primary endpoint result is not reported in the registry record. Although the endpoint definition and success threshold are available, the observed proportion, participant count, and precision are not. The principal immunogenicity question therefore cannot be answered from the posted results described in the record.
Second, the study was open-label, uncontrolled, and single-group. No randomized comparator is listed, so the study does not provide a like-for-like control comparison. The two parts have separate labels and participant counts in the safety summaries, but are not described as randomized arms.
Third, the endpoint refers to toxin A and toxin B without reporting the exact rule for combining the measurements into the participant-level response. The primary population and missing-data procedures are also not reported. This leaves the endpoint denominator and handling of incomplete Week 0 or Week 4 measurements unclear.
Fourth, safety reporting is limited in the listed summaries. Serious adverse event counts are given, as are participant counts for other adverse events, but the event terms, severity, timing, attribution, and death counts are not reported in the registry record.
Finally, the registry lists secondary outcomes but reports no analyses. A multiplicity approach and detailed statistical plan are not reported. The planning assumptions are identified as illustrations rather than the trial’s design, and do not fill those gaps.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety, Tolerability, and Immunogenicity Study of Investigational Recombinant Botulinum Vaccine A/B (rBV A/B) in Volunteers Previously Immunized With Investigational Pentavalent Botulinum Toxoid — NCT01701999.
- Registry record last updated 2017-05-16; status last verified 2017-04.
- Results first posted 2017-02-09.
- 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.
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18. Record Summary
This completed Phase 2b study evaluated a single 40-µg dose of rBV A/B in volunteers previously immunized with pentavalent botulinum toxoid. It was open-label, uncontrolled, and single-group, with 45 participants enrolled. The registry describes two parts: Initial Safety and Immunogenicity, and Safety, Immunogenicity, and Plasma Collection.
The primary endpoint was the proportion achieving a four-fold or greater increase in NAC from Week 0 to Week 4 for toxin A and toxin B; a proportion of at least 0.50 was considered a success. The primary result is not reported in the registry record. The registry lists zero serious adverse events in each part, and other adverse events affecting 8 of 8 participants in Part 1 and 34 of 37 in Part 2. Death counts are not reported.
The study started in 2013-02 and reached primary completion in 2015-06. The sponsor is the California Department of Public Health. Detailed statistical methods, analysis-population definitions, missing-data procedures, and a multiplicity plan are not reported in the registry record.