GLS-5700 in Dengue Virus-Naïve Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for GLS-5700 in Dengue Virus-Naïve Adults (NCT02809443), a non-randomized phase 1 study. The primary outcome is Number of Participants With Serious Adverse Events From Day 0 Through Week 60.

2. Clinical Question

The trial record describes a Phase I, open-label, dose-ranging study in dengue virus-naïve adults. Its stated aims include assessing safety, tolerability, and immunogenicity of GLS-5700. The brief summary identifies GLS-5700 as a Zika virus vaccine; the secondary outcomes listed are binding antibody response to Zika envelope and T cell response.

The primary endpoint specifically counts participants with serious adverse events over the stated period. It does not itself measure whether the vaccine elicited an immune response, nor does the listed count provide a comparison with an untreated group. The posted safety figures give the number of participants at risk and the number affected in each dose group. Both dose groups report zero participants with a serious adverse event.

The record does not report an inferential comparison between dose groups or detailed results for the secondary immune-response outcomes. Consequently, the central statistical question answerable from the posted primary endpoint is descriptive: how many participants in each listed group were recorded as having a serious adverse event during the specified period. The record does not establish whether any difference between doses is meaningful, or how the safety counts compare with what might occur without GLS-5700.

3. Trial Design

This was a Phase I, open-label, dose-ranging study. The registry record lists a parallel model, non-randomized allocation, and no masking. Enrollment was 40, with two listed groups: GLS-5700 at 1 mg and GLS-5700 at 2 mg. The serious adverse event results list 20 participants at risk in each group. The record does not describe a placebo or no-treatment group.

The official title says GLS-5700 was administered intradermally followed by electroporation in dengue virus-naïve adults. The listed condition is Healthy, and the brief summary describes the product as a synthetic DNA plasmid vaccine against Zika virus. The study aimed to assess safety, tolerability, and immunogenicity. Its secondary outcomes include binding antibody response to Zika envelope and T cell response.

The record gives a start date of 2016-07 and a primary completion date of 2017-11, and lists the study status as Completed. The primary safety outcome covers Day 0 through Week 60. Details such as the exact schedule of administration, participant eligibility criteria beyond the description in the title, and follow-up procedures are not reported in the registry record.

Non-randomized allocation means the groups were not assigned by random allocation according to the registry entry. Open-label means the record does not describe masking. These features matter when reading a comparison: the two dose groups are not equivalent to randomized treatment and control arms. Differences, if any, could reflect factors other than dose, while a lack of an observed difference would not establish that the doses have the same safety profile. The record does not report a statistical plan explaining how dose groups were to be compared.

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

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 Participants With Serious Adverse Events From Day 0 Through Week 60, measured over Day 0 through Week 60.

The primary endpoint is the number of participants with serious adverse events from Day 0 through Week 60. Its unit is participants, so the result is a count of people who experienced at least one event meeting the study's serious-adverse-event classification during the stated period. The record does not give a more detailed endpoint definition or criteria for classifying seriousness.

Counting affected participants is a direct way to describe how many people experienced a specified safety outcome. It differs from counting the total number of events: one participant could experience more than one event, but the endpoint as titled counts participants. The posted figures therefore answer a participant-level question, not how often events occurred, how long they lasted, or how severe they were beyond the serious classification.

This endpoint is relevant to the study's stated safety aim. However, it is only one component of safety assessment. It does not capture all tolerability outcomes or all adverse events, and a zero count does not establish that no safety concerns of any kind occurred. The registry record separately lists other adverse event counts, but those counts are not the primary endpoint and should not be conflated with serious adverse events.

The timeframe is important to interpretation: the primary outcome is limited to Day 0 through Week 60. The registry record does not report participant-level follow-up completeness or the method used to handle any missing safety observations. The count should therefore be read as the posted result for the stated outcome and period, rather than as a complete characterization of safety beyond that period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The reported primary outcome is a binary participant-level event summarized as a count: a participant either did or did not have a serious adverse event during the specified period. The registry presents the number affected and the number at risk in each group. This is a descriptive summary. It does not by itself estimate a causal effect of one dose relative to another.

What does a confidence interval add?

As general statistical context, an estimate based on a finite group of participants is subject to sampling uncertainty. A confidence interval expresses a range of values compatible with the observed data under a stated statistical method. For a binary outcome, uncertainty depends on both the observed event count and the number of participants observed. When no events are observed, uncertainty remains: the data do not prove that the underlying event probability is zero. The registry record does not report confidence intervals for the serious adverse event counts.

Why does the study design affect comparisons?

As general statistical context, random allocation is used to make treatment groups more comparable with respect to measured and unmeasured characteristics, on average. This study is listed as non-randomized and open-label, with a parallel model. The two dose groups are therefore not a randomized control comparison. Any apparent difference between groups could be related to group composition or other factors, rather than dose alone. A descriptive comparison is still possible, but causal interpretation requires stronger assumptions than a randomized comparison generally does.

The record does not report how participants were assigned to the dose groups, whether assignment was based on sequence or other criteria, or whether any covariates were accounted for in analysis. It also does not report adjusted estimates. Those details should not be inferred from the dose labels or the parallel design.

What can the posted counts establish?

The count of affected participants describes what was recorded in each group for the stated endpoint and timeframe. It does not show the number of events per participant, the timing of events, or the severity of events outside the serious category. The other adverse event counts are reported separately. General statistical interpretation also distinguishes observing no events from demonstrating equivalence: equivalence requires a defined margin and an appropriate analysis, neither of which is reported in the registry record.

The registry record gives no p-value or statistical test for comparing the groups. It does not report a model for the primary endpoint, a prespecified hypothesis, or an adjusted analysis. A p-value, if one were reported, would address compatibility of the data with a specified statistical hypothesis under the test assumptions; it would not by itself establish clinical importance or eliminate design limitations. No such inferential result is available in this record.

How should sample-size illustrations be understood?

As general statistical context, a sample-size calculation is a planning exercise tied to assumptions about the event rate, the effect worth detecting, the significance level, power, allocation, and analysis method. It is not a result observed in participants. The registry record describes its sample-size assumptions as an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. It specifies that the effect to detect is a stated fraction of the observed effect. Such assumptions do not turn the study's enrollment into observed power, and no sample-size illustration should be read as proof that an effect was detected or excluded.

In general, power refers to the probability that a prespecified analysis will reject a null hypothesis when a particular alternative is true. It is a property of a design and its assumptions, not a retrospective measure of whether a trial's result is reliable. A small or zero event count can leave considerable uncertainty even when a planning calculation is shown. No separate sample-size justification or design rationale is reported in the registry record.

What details remain unavailable?

The registry record does not report the statistical analysis plan for the primary endpoint, the exact serious adverse event definition, how incomplete follow-up was handled, or whether any interim analyses occurred. It lists no analyses. The record also does not report confidence intervals, model estimates, or a statistical comparison of the dose groups. In the absence of those details, the sound interpretation is limited to the recorded counts and the design information explicitly stated in the registry.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("GLS-5700 at 1 mg", "GLS-5700 at 2 mg")
n      <- c(20, 20)
events <- c(0, 0)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  GLS-5700 at 1 mg  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1
ARM  GLS-5700 at 2 mg  20  0  0.0  0.0  16.8  0.0  16.1  0.1  16.1

11. Multiplicity, Missing Data and Analysis Populations

The trial lists a primary safety outcome and secondary outcomes for binding antibody response to Zika envelope and T cell response. Considering several outcomes can raise a multiplicity issue: as general statistical context, when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of tests. The registry record does not report a multiplicity adjustment, a hierarchy among secondary outcomes, or a prespecified strategy for interpreting multiple tests.

The record lists three outcome measures and zero analyses. It does not report statistical test results for the primary endpoint or the secondary immune-response outcomes. It is therefore not possible to determine whether the outcomes were analyzed according to a prespecified plan, or whether any correction for multiple comparisons was used.

Missing-data handling is also not reported in the registry record. The safety summary lists 20 participants at risk in each dose group, but this does not establish that every participant completed the full follow-up period or that no observations were missing. The record does not describe how withdrawals, incomplete follow-up, or unavailable outcome measurements were treated.

Analysis populations are not reported in the registry record. It is not specified whether the primary outcome was summarized for all enrolled participants, a safety population, or another defined group. The participant counts in the safety results describe the posted denominators, but do not identify a broader analysis rule. These gaps matter because outcome definitions, missing-data procedures, and population rules affect how results should be interpreted and compared.

12. 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 non-serious adverse event terms

For serious adverse events from Day 0 through Week 60, the registry reports zero affected participants among 20 at risk in the GLS-5700 at 1 mg group, and zero affected participants among 20 at risk in the GLS-5700 at 2 mg group. The deaths count is also zero in each group. These are counts, not estimates of risk with reported confidence intervals.

The other adverse event count is 20 among 20 participants in each group. It is reported separately from the serious adverse event count. A participant may be included in an other adverse event category without having a serious adverse event; the registry's figures do not mean that all other events were serious. The record does not give detailed event terms in the information.

Read the denominators with the counts: they indicate the participants listed as at risk for each category. They do not provide details about follow-up completeness or the number of events per participant. The primary outcome counts participants with at least one serious event, rather than the total number of serious events.

Zero recorded serious events is a descriptive finding, not proof that the underlying risk is absent. The study is non-randomized, open-label, and has no listed control group, so these figures should not be read as a comparative estimate of treatment effect.

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

The result establishes a limited descriptive fact: the registry reports zero participants with serious adverse events in each of the two GLS-5700 dose groups over Day 0 through Week 60. The reported at-risk count is 20 for each group. The record also lists zero deaths in each group and 20 participants with other adverse events in each group.

These observations do not establish that GLS-5700 has no risk of serious adverse events. A study can record no events while uncertainty about the underlying event probability remains. No confidence interval or other uncertainty measure for the primary outcome is reported, and the registry entry does not provide enough information to assess follow-up completeness.

The results do not establish that the 1 mg and 2 mg doses are equivalent or that one is safer than the other. The study is non-randomized and open-label, and the registry record lists no control group. The posted counts are not a randomized causal comparison. The record also does not report a statistical test or adjusted comparison between doses.

Nor do the serious adverse event counts answer the study's immunogenicity questions. The listed secondary outcomes concern binding antibody response to Zika envelope and T cell response, but their results are not reported in the registry information. A safety count cannot substitute for those immune-response measurements. Likewise, the other adverse event count alone does not describe event types, duration, or severity.

The study is identified as a Phase I dose-ranging investigation with stated aims of assessing safety, tolerability, and immunogenicity. The posted primary result can inform a narrow description of recorded serious events in the listed groups and timeframe. It cannot, on its own, establish comparative safety, exclude uncommon harms, characterize longer-term outcomes beyond Week 60, or answer whether an immune response occurred. Those conclusions require information and analyses not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates how the form of an endpoint shapes the conclusion that can be drawn. The primary outcome counts participants with serious adverse events, so the posted result answers a specific safety question over a specified period. It is not a general measure of tolerability, all adverse events, or immunogenicity. Keeping those outcome categories distinct is important when interpreting a registry summary.

The record also shows why study design is part of statistical interpretation. Although two dose groups are listed in a parallel study, allocation is non-randomized and the trial is open-label. The groups are therefore not interchangeable with randomized treatment and control arms. Their counts can be described side by side, but they do not establish a causal difference between doses.

A zero count can appear definitive while still leaving uncertainty about uncommon outcomes. Without a reported confidence interval, analysis plan, or detail about follow-up completeness, the precision of the primary safety result cannot be fully evaluated. The observed counts remain useful as a record of what was reported, but their scope should not be overstated.

Finally, the trial's stated aims extend beyond the primary safety endpoint to immunogenicity. The registry lists immune-response outcomes, but the results summarized in the record do not report their findings. This distinction highlights a general statistical principle: a result answers only the endpoint actually measured and reported. Describing both the available information and the missing analyses helps readers avoid treating one kind of evidence as an answer to a different question.

15. 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 gives limited detail about the methods underlying the reported safety counts. It does not report the statistical analysis plan, the definition used for serious adverse events, or the procedure for determining whether an event met that definition. It also does not report participant-level follow-up completeness or how missing safety observations were handled.

The study's non-randomized allocation and open-label design limit comparisons between the two dose groups. The registry record does not list a placebo or untreated control group, and it does not report how participants were assigned to doses. Therefore, the posted counts cannot establish that any difference between groups was caused by dose, nor can the study's listed groups provide a direct comparison with no intervention.

The safety results are counts, and no confidence intervals, p-values, or model estimates are reported. There is no inferential comparison of the groups in the registry record. The listed secondary outcomes address antibody and T cell responses, but results for those measures are not reported in the information. This limits assessment of the trial's stated immunogenicity aims.

The record identifies the primary endpoint timeframe as Day 0 through Week 60, but does not describe outcomes beyond that period. It also does not provide detailed event terms for the other adverse event counts in the information. Consequently, the posted safety summary does not characterize event types, timing, duration, or severity beyond the serious versus other categories.

Finally, enrollment and the at-risk counts describe the recorded study groups, but the registry information does not report a sample-size justification or establish the study's ability to detect a particular safety difference. The sample-size assumptions are described as a planning illustration, not as observed power. These limits make descriptive interpretation more appropriate than broad comparative or definitive claims.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: GLS-5700 in Dengue Virus-Naïve Adults — NCT02809443.
• Registry record last updated 2024-12-24; status last verified 2024-11.
• Results first posted 2024-12-24.
• 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.

19. Record Summary

The registry record identifies NCT02809443 as a completed Phase I, open-label, non-randomized, parallel dose-ranging study of GLS-5700 in dengue virus-naïve adults. The official title describes intradermal administration followed by electroporation. Enrollment was 40, with listed groups receiving GLS-5700 at 1 mg or 2 mg.

The primary outcome counts participants with serious adverse events from Day 0 through Week 60. The posted results report zero affected participants among 20 at risk in each group, and zero deaths in each group. Other adverse events are reported for 20 participants in each group.

The study's stated aims include safety, tolerability, and immunogenicity. Secondary outcomes listed are binding antibody response to Zika envelope and T cell response. Their results, statistical comparisons, and analysis details are not reported in the registry record. The safety counts are descriptive and do not establish comparative dose effects.