Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR) (NCT02445963), a non-randomized phase 1 study. The primary outcome is Number of Treatment Related Adverse Events.

2. Clinical Question

The clinical question is primarily about safety and immunogenicity in healthy adult volunteers, not about prevention of shigellosis in people at risk of infection. The registry identifies the intervention as a biological product and describes administration by the intranasal route, without adjuvant. Its dose-escalating design evaluates four stated dose levels, with vaccination on days 0, 14, and 28.

Immunogenicity is represented by listed secondary outcomes concerning IgG and IgA antigen-specific antibody-secreting cell mucosal responses and IgG and IgA antigen-specific antibody lymphocyte-supernatant mucosal responses. The registry record does not provide numerical results for these outcomes in the registry entries. The primary endpoint is the number of vaccine-related adverse events over 166 days. The available safety figures instead describe counts of participants affected by serious or other adverse events. Those figures are relevant to safety context but are not interchangeable with the primary event-count endpoint.

3. Trial Design

The registry describes a Phase 1, open-label, dose-escalating study of artificial S. flexneri 2a InvaplexAR, administered intranasally to healthy adult volunteers. The allocation is non-randomized, masking is absent, and the study model is parallel. The listed intervention is S. flexneri 2a InvaplexAR, and the brief summary states that it was administered without adjuvant.

Four arm descriptions specify doses of 10 μg, 50 μg, 250 μg, and 500 μg. Each description says vaccination occurred on days 0, 14, and 28, and specifies 10 subjects. The registry record separately lists enrollment as 38 and the brief summary says up to 40 subjects would receive one of four doses. These are different entries in the record; the record does not explain their relationship. The dates listed for study start and primary completion are 2015-10-01 and 2016-05-13, and the status is completed.

Because allocation was not randomized and masking was absent, the dose groups should not be interpreted as randomized treatment-versus-control arms. Differences between groups, if considered, may reflect factors other than dose. The registry record does not report how dose escalation was implemented, what criteria governed movement between dose levels, or whether any group served as a concurrent control.

The stated primary endpoint is the number of vaccine-related adverse events for each arm during 166 days. Secondary outcomes concern mucosal antibody responses measured through listed IgG and IgA assays. The record lists four outcome measures and no analyses. It does not report an analysis population, a statistical analysis plan, or numerical immunogenicity results in the available 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:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Treatment Related Adverse Events, measured over 166 days.

The primary endpoint is titled “Number of Treatment Related Adverse Events.” It is defined as the number of adverse events related to the vaccine for each arm, with a timeframe of 166 days. This is an event-count endpoint: its intended quantity is the count of events judged to be related to the intervention, rather than simply the number of participants who experienced any event.

Such an endpoint is used in an early-phase study to describe the safety experience during the specified follow-up period. Event counts can capture repeated events in the same participant, so they may differ from counts of affected participants. Interpretation depends on how events were collected, how treatment relatedness was assessed, and how the count was analyzed. Those details are not reported in the registry record.

The posted safety figures report participants at risk and participants affected by serious or other adverse events. They do not give the number of treatment-related adverse events for each arm. Therefore, the serious and other event figures should not be substituted for the primary endpoint, and they cannot establish how many events were judged treatment related. The record does not report a numerical result for the primary endpoint in the registry entries.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record characterizes the study as non-randomized, open-label, and parallel, with dose escalation. Those design labels shape what statistical conclusions can be drawn. No statistical analysis is listed, and no model, test, confidence interval, or adjustment procedure is reported. The explanations below describe general statistical ideas relevant to this type of study; they are not claims about methods used in this trial.

What does a count endpoint represent?

General: A count endpoint records how many events occur during a defined period. For an adverse-event count, the distinction between the number of events and the number of participants experiencing events is important. A participant can contribute more than one event, while a participant-level summary records whether a person experienced an event, regardless of recurrence. The primary endpoint is defined as a number of treatment-related adverse events per arm over 166 days, but the posted safety figures report affected participants for serious and other events instead.

General: Count data are often analyzed with models designed for nonnegative event counts. A Poisson model is one common option, but it assumes a relationship between the mean and variance that may be too restrictive if event counts vary more than expected under that model. This is called over-dispersion. If over-dispersion is present, a model that accounts for it may produce more appropriate uncertainty estimates. The registry record does not report whether a count model was used, whether over-dispersion was assessed, or how treatment-related events were analyzed.

Why does the study design matter?

General: Random allocation can help balance both measured and unmeasured characteristics across groups, supporting a causal interpretation of between-group differences. In a non-randomized study, group membership may be associated with other differences among participants or with study procedures. Open-label conduct also means treatment assignment is not masked. These features do not make descriptive safety reporting impossible, but they limit how confidently group differences can be attributed to dose.

General: A parallel design means groups are observed as separate study arms rather than the same participants receiving every dose in a crossover sequence. The registry lists dose groups, but does not report a control arm. Dose escalation describes increasing dose levels in the study, but the registry record does not describe the sequence, decision rules, or safeguards used for escalation. Statistical comparison across dose groups should not be interpreted as randomized evidence.

What would an estimate and its uncertainty tell a reader?

General: An estimate summarizes the observed quantity, such as an event rate or a difference between groups. A confidence interval describes the range of values reasonably compatible with the data under the assumptions of the analysis. A narrow interval indicates greater precision than a wide interval; neither an estimate nor an interval alone resolves design limitations or proves a causal effect. No estimates or confidence intervals for the primary endpoint are reported in the registry record.

General: A p-value is a measure of how unusual data would be under a specified statistical model and null hypothesis. It is not the probability that the null hypothesis is true, and it does not describe the size or clinical importance of an effect. The registry record lists no analyses or p-values, so there is no reported hypothesis-test result to interpret.

How should planning illustrations be understood?

General: A sample-size calculation uses assumptions about the effect to be detected, the allocation, the significance level, and the statistical method. It is a planning exercise, not a measure of the evidence observed in a completed study. The record describes a planning illustration based on a fraction of an observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It also distinguishes calculations expressed per arm from event totals for time-to-event calculations. The calculated planning values and the observed effect needed to interpret them are not reported in the registry record.

Such calculations cannot be treated as observed power. Observed power is not a substitute for reporting an effect estimate and its uncertainty. The study’s actual enrollment and the arm descriptions do not establish a sample-size justification: that justification is not reported in the registry record. The record also does not state that the planning assumptions were part of the trial’s original design.

What can be inferred from the posted safety figures?

General: Counts of affected participants provide descriptive information about how many people had a recorded type of event. They do not reveal the total number of events, duration, severity beyond the stated category, or relatedness unless those details are separately reported. For comparisons, denominators and consistent follow-up are important. The record provides at-risk and affected-participant counts for serious and other adverse events, but does not report the event-level detail or endpoint-specific analysis needed to estimate a treatment-related event count.

In this record, no inferential analysis is listed. That absence is not evidence that a particular statistical method was unsuitable or that an analysis was not conducted outside the registry. It means the registry record does not provide the method or result for interpretation. Any statistical account should therefore remain descriptive and should keep the listed participant-level safety summaries separate from the defined primary event-count endpoint.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures, including the primary endpoint and named secondary mucosal-response outcomes for IgG and IgA antibody-secreting cell and antibody lymphocyte-supernatant responses. It reports no analyses. The multiplicity strategy—how the possibility of multiple outcomes or comparisons was addressed—is not reported in the registry record. Without that information, it is not possible to determine whether any statistical testing was planned, whether results were adjusted, or how exploratory findings were distinguished from confirmatory ones.

The record does not report an analysis population, such as which participants were included in each endpoint analysis. It also does not report participant flow through follow-up, endpoint-specific denominators, missing-data handling, or whether observations were excluded. These details matter because missingness can affect both the estimate and its uncertainty, particularly if missing observations are related to treatment, adverse events, or immune response.

The record lists enrollment as 38, while the arm descriptions specify 10 subjects for each dose group and the brief summary says up to 40 subjects. It does not explain how these entries correspond to the analyzed populations or whether all enrolled participants received every scheduled vaccination or completed follow-up. No reconciliation should be assumed.

The registry record does not report the statistical analysis plan, sample-size justification, interim analyses, or procedures for handling repeated or correlated measurements. It also does not provide numerical results for the listed immunogenicity outcomes. These omissions limit assessment of selective reporting, the completeness of outcome data, and the precision of any comparisons.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event figures report zero affected participants in each dose group. The at-risk counts are 9 for the 10 μg group, 9 for the 50 μg group, 10 for the 250 μg group, and 10 for the 500 μg group. The record also lists zero deaths in each group. These figures describe the registry’s serious-event and death entries; they do not prove that no other safety concerns occurred.

For other adverse events, the affected-participant counts are 9 in the 10 μg group, 9 in the 50 μg group, 10 in the 250 μg group, and 10 in the 500 μg group. The registry record does not say that these other events were treatment related. It also does not provide event totals, event descriptions, severity grades, duration, or participant-level timing in the registry entries.

These summaries should not be confused with the primary endpoint, which is the number of treatment-related adverse events over 166 days. The figures concern participants affected by serious or other events, not the number of events judged related to the vaccine. Definitions and adjudication procedures are not reported in the registry record, so the summaries support only a limited descriptive reading.

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

The registry record describes a completed early-phase study of intranasal S. flexneri 2a InvaplexAR in healthy adult volunteers, with four dose levels and a primary safety endpoint defined as the number of treatment-related adverse events during 166 days. The posted safety figures record zero participants affected by serious adverse events in each group and zero deaths in each group. They also record participants affected by other adverse events in every group.

Those observations do not establish that the intervention is safe or unsafe in a broader population. The record does not give the primary endpoint’s event counts, establish that other events were related to the vaccine, or provide comparative analyses. Its non-randomized, open-label design also limits causal interpretation of differences between dose groups. The registry does not identify a placebo or untreated control group.

The study is not described as a clinical efficacy trial, and the registry entries do not report clinical outcomes that would establish prevention or treatment of shigellosis. The registry lists mucosal antibody-response outcomes, but their numerical results are not reported in the registry record. The study therefore cannot, from these registry entries alone, establish the magnitude, precision, or clinical significance of an immune response.

The findings are best understood as limited descriptive safety information from the listed groups. The record does not report the treatment-related event totals, analysis methods, missing-data procedures, or outcome-specific populations needed for a fuller statistical assessment. Nor does it report a sample-size justification or the protocol details needed to assess how dose escalation was conducted. These gaps constrain what the posted results can support; they do not justify filling in unreported methods or outcomes.

In general, early-phase studies can characterize observations under study conditions and inform further research questions. That general role does not convert descriptive group counts into evidence of a causal dose effect. The record should be interpreted within its stated population, intervention, design, follow-up timeframe, and reporting limits.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it places a count-based safety endpoint alongside participant-level summaries. The primary endpoint concerns the number of vaccine-related adverse events, while the posted safety figures report how many participants were affected by serious or other events. Keeping these quantities separate prevents a participant count from being mistaken for an event total or for a treatment-related endpoint result.

The design also illustrates why a dose sequence is not the same as randomized dose comparison. With non-randomized allocation and no masking, differences among dose groups can be described, but the record does not support attributing them to dose alone. A parallel arrangement makes the groups distinct; it does not make them exchangeable for causal comparison.

The record’s reporting gaps are important to statistical interpretation. No analyses are listed, and the numerical result for the primary endpoint and the listed immunogenicity outcomes are not reported in the registry entries. Without estimates, uncertainty measures, and analysis details, readers cannot assess precision, multiplicity, or the handling of missing data. Clear reporting of these elements is necessary to distinguish a descriptive observation from a supported comparison.

Finally, the record lists enrollment as 38, describes 10 subjects in each dose group, and states that up to 40 subjects would receive a dose. It does not explain the relationship among those entries. Preserving that distinction rather than silently reconciling the figures is part of responsible registry interpretation. The study offers a useful case for separating design description, endpoint definition, and posted safety summaries from conclusions the record cannot establish.

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 registry record does not provide a numerical result for the primary endpoint, despite defining it as the number of treatment-related adverse events per arm over 166 days. The available safety entries are participant counts for serious and other adverse events, not event totals or judgments of treatment relatedness. Event definitions, severity grading, and relatedness assessment procedures are not reported in the registry record.

The non-randomized, open-label design limits causal interpretation of comparisons across dose groups. A control group is not described, and the record does not report the dose-escalation sequence or the criteria used to progress between doses. The study population is described as healthy adult volunteers, so the record does not establish how these observations apply to other populations.

There is an unresolved difference among the listed enrollment of 38, the arm descriptions specifying 10 subjects each, and the brief summary’s statement of up to 40 subjects. The registry record does not explain the relationship among these figures. It also does not report group-specific endpoint denominators, follow-up completion, exclusions, or missing-data handling.

Although mucosal antibody-response outcomes are listed, their numerical results are not reported in the registry record. No analyses are listed, and the statistical plan, multiplicity handling, sample-size justification, and interim-analysis procedures are not reported. The record therefore supports a limited descriptive reading of the available safety figures, not a full assessment of comparative effects or statistical precision.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of Artificial Invaplex (Shigella Flexneri 2a InvaplexAR) — NCT02445963.
• Registry record last updated 2021-02-12; status last verified 2021-02.
• Results first posted 2020-07-22.
• 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

The registry record describes a completed, non-randomized, open-label, parallel Phase 1 dose-escalation study of intranasal S. flexneri 2a InvaplexAR without adjuvant in healthy adult volunteers. Four dose groups are described: 10 μg, 50 μg, 250 μg, and 500 μg, with vaccination on days 0, 14, and 28. The listed primary endpoint is the number of vaccine-related adverse events during 166 days.

Safety figures report zero participants affected by serious adverse events and zero deaths in each group. Other adverse events affected participants in each group, but treatment relatedness and event totals are not reported. The record lists mucosal IgG and IgA outcomes, but their numerical results are not reported in the registry record. No analyses are listed. The record’s design and reporting limits prevent causal or comparative conclusions from these descriptive figures.