Trial for Safety and Immunogenicity of a Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Trial for Safety and Immunogenicity of a Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults (NCT02562482), a randomized phase 2 study. The primary outcome is Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Injection.

2. Clinical Question

The trial was designed to assess safety and immunogenicity, not to answer a question about clinical protection against chikungunya infection. Its primary endpoint concerns local reactogenicity: signs and symptoms recorded by participants after injections. The record also lists chikungunya antigen-specific neutralizing antibody geometric mean titers as secondary outcomes in the per-protocol, intent-to-treat, and modified intent-to-treat populations.

The available record does not include numerical results for those antibody outcomes. It also does not reduce the primary outcome to one comparison: the endpoint includes multiple symptom and severity categories. The clinical question can therefore be described from the design, but the posted information does not establish how the vaccine group’s primary-endpoint results compare with placebo.

3. Trial Design

This was a phase 2, randomized, placebo-controlled, parallel-group trial in healthy adults. The registry identifies the masking as triple; the study summary describes the trial as double-blind. It does not explain the roles covered by the masking designation. The study is described as multicenter and was sponsored by the National Institute of Allergy and Infectious Diseases.

The registry records enrollment of 400. Participants were assigned to receive either VRC-CHKVLP059-00-VP at 20 micrograms or phosphate buffered saline placebo. Both groups were scheduled for two intramuscular injections at Day 0 and Day 28 (+14 days). The primary completion date was 2018-03-06, and the study status is completed. The start date was 2015-11-18.

The primary outcome assessed the number of participants reporting local reactogenicity signs and symptoms within 7 days of any injection. Symptoms were recorded on a memory aid and reviewed with clinic staff at a follow-up visit. Participants were counted once for each symptom at its worst severity if they reported that symptom at any severity during the reporting period. Severity grading followed the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials (FDA Guidance - September 2007).

Three secondary outcomes concern chikungunya antigen-specific neutralizing antibody geometric mean titers, each specified for a different analysis population. The registry lists 9 outcome measures overall. It does not report a statistical analysis plan or a sample-size justification. The design details alone do not establish what numerical differences were observed or how precisely any treatment contrast was estimated.

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: Population included all enrolled subjects who received at least one injection and provided safety data (via diary card and/or laboratory results) following the injection. Four subjects in Group 1 did not receive product and one subject in Group 2 did not provide a diary card following the first injection and were excluded from analysis.

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: Population includes all enrolled subjects.

6. Primary Endpoint

The registry lists the primary outcome as Number of Subjects Reporting Local Reactogenicity Signs and Symptoms Within 7 Days of Any Injection, measured over 7 days after any injection.

The primary endpoint counts participants who reported solicited local signs or symptoms within 7 days after any injection. It captures short-term local reactions following vaccination or placebo administration. The endpoint is a participant count, not a measure of symptom duration or a continuous severity score. For each symptom, a participant is counted once at the worst severity reported during the specified period.

Solicited symptoms were recorded on a memory aid and reviewed with clinic staff at a follow-up visit. The endpoint description states that reactogenicity was recorded without an attribution assessment. Thus, a reported symptom is counted according to the endpoint definition; the count itself does not establish that the injection caused the symptom. Severity categories were graded using the stated FDA guidance.

This type of endpoint is used to describe the frequency and severity of prespecified short-term reactions in the trial population. Reporting counts by symptom and severity can retain distinctions that would be lost in a single combined count. However, the registry record does not include the underlying primary-outcome results or a single vaccine-versus-placebo estimate. It notes that the outcome has several categories or time points and was not reduced to one comparison. As a result, the endpoint’s definition is available, but its group-specific results cannot be interpreted from the record.

The safety population definition includes enrolled participants who received at least one injection and provided safety data through a diary card and/or laboratory results. The record notes that four participants in Group 1 did not receive product and one participant in Group 2 did not provide a diary card following the first injection. The endpoint information does not explain how each such case was handled for every symptom category.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting clinical trial statistics requires distinguishing the endpoint definition, the population analyzed, the numerical estimate, and its uncertainty. For this trial, the registry gives a detailed definition of the primary local-reactogenicity endpoint and selected adverse-event counts, but the primary endpoint is not presented as one group comparison. Without that comparison and its uncertainty, the endpoint definition cannot answer how the groups differed.

What does a participant count mean?

A count of participants with an event records how many people met a specified event definition during the observation period. In this trial, the primary outcome counts each participant once for each symptom at the worst severity reported. That approach avoids counting repeated reports of the same symptom as separate participants, while retaining distinctions among symptoms and severity categories. It is still necessary to know the denominator for each category and the rules for handling missing reports to interpret a count fully.

For adverse events, the registry lists participants at risk and participants affected in each group. Those figures are descriptive and depend on the event classification used in the record. A count does not, by itself, quantify uncertainty or establish a causal relationship. Random allocation supports a planned comparison between groups, but a statistical estimate still requires an explicitly reported outcome contrast and its analysis details.

Why does the endpoint’s structure matter?

The primary endpoint contains several symptom categories and severity levels, and the registry indicates that it was not reduced to one comparison. A single combined result could conceal which symptoms or severity categories contributed to the total. Conversely, examining many separate categories can make interpretation more complex. The record does not report the complete category-level results or explain a planned strategy for drawing conclusions across those categories.

When counts are compared, the denominator and analysis population must match the outcome definition. The primary safety population is described as enrolled participants who received at least one injection and provided safety data. The adverse-event listing gives separate at-risk counts for each group. The record does not state whether every outcome used precisely the same population or how any differences in available data were handled.

What would uncertainty measures add?

A confidence interval is a statistical range that conveys the precision of an estimated effect under the assumptions of the analysis. A narrow interval generally indicates more precise estimation than a wide interval, while the interval’s location indicates which effect values remain compatible with the data. A p-value addresses compatibility between the observed data and a specified null model; it is not a measure of clinical importance. Neither kind of result replaces the need to report the estimate itself and explain the outcome definition.

No confidence interval or p-value for the primary endpoint is reported in the registry record. The registry record also does not give analysis-level results for the listed neutralizing antibody outcomes. Therefore, no inferential conclusion about those endpoints can be reconstructed from the event counts alone. A new calculation would require suitable outcome summaries and clearly defined analysis methods.

How should planning calculations be read?

The stated planning illustrations use a two-sided significance level of 0.05, equal allocation between the arms, and a normal approximation. They use an effect set as a stated fraction of the observed effect. For non-time-to-event outcomes, such calculations are expressed as participants per arm; time-to-event calculations use a total number of events. These assumptions describe illustrations, not necessarily the trial’s original design decisions.

A sample-size illustration is a planning aid: it indicates the sample size associated with selected assumptions about an effect and analysis. It is not observed power, and it does not show that a trial had a particular chance of producing a significant result after the data were collected. The record does not report the trial’s own sample-size justification. With the primary endpoint unreduced to one comparison, no single primary-outcome effect can be interpreted from this record as the basis for such an illustration.

Why is over-dispersion relevant in general?

For count outcomes, a statistical model may assume that variability follows a specified relationship to the average count. Over-dispersion means the observed variability is greater than that model expects. If it is ignored, standard errors can be too small and confidence intervals or tests can be misleading. This is a general statistical consideration, not a reported feature of this trial. The registry record does not identify a count model, an over-dispersion assessment, or an analysis plan for the primary endpoint.

More broadly, the record does not describe interim analyses, adjustment methods, covariates, or model diagnostics. Those details are not reported in the registry record. The design and outcome definitions can be discussed, but statistical methods beyond those explicitly described should not be inferred.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when an analysis considers several outcomes, symptom categories, severity levels, populations, or comparisons. The more questions examined, the greater the risk that an apparently notable result may arise by chance if no strategy for interpreting the collection of results is specified. This trial’s primary endpoint includes multiple symptom and severity categories, and the registry lists several antibody outcomes across distinct analysis populations. The record does not report a multiplicity-adjustment plan or a hierarchy for interpreting these outcomes.

Missing data also matter because the primary endpoint depends on participant symptom reports. The registry describes memory aids and follow-up review, and notes that one participant in Group 2 did not provide a diary card following the first injection. It also notes that four participants in Group 1 did not receive product. The record does not explain the full handling of missing symptom reports, the amount of missing data by outcome, or whether any imputation or sensitivity analysis was used.

The antibody outcomes are listed for per-protocol, intent-to-treat, and modified intent-to-treat populations. The registry record does not give their detailed definitions, the numbers included in each population, or results for any of them. It also does not describe how participants with incomplete antibody measurements were treated. These omissions prevent assessment of how analysis-population choices may affect those results.

The registry lists 0 analyses. A complete statistical plan, including missing-data procedures and multiplicity handling, is not reported in the registry record. The absence of those details is a limit on interpretation, not evidence that no such procedures were used outside the record.

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: pre-eclampsia (0.5%), appendicectomy (0.5%), pyelonephritis (0.5%), colitis (0.5%), femur fracture (0.5%).

The registry reports serious adverse events for 4 of 197 participants at risk in the vaccine group and 11 of 198 in the placebo group. For other adverse events, it reports 123 of 197 and 128 of 198, respectively. The record lists 0 deaths in both groups. These figures should be read as counts of participants affected within the registry’s event categories, rather than as adjusted estimates of a treatment effect.

The serious-event terms listed are Pre-eclampsia, Appendicectomy, Pyelonephritis, Colitis, Femur fracture, and Polycystic ovaries. Each term is listed as 0.5%. The registry does not report a causal attribution for these terms. Their listing does not establish that an intervention caused an event, and the available information does not explain whether the list is exhaustive or how overlapping events were handled.

The serious and other adverse-event counts do not substitute for the primary reactogenicity outcome. The latter concerns solicited local symptoms within 7 days of any injection and is organized by symptom and worst severity. Its complete group-specific results are not reported as one comparison in the record. No confidence intervals or inferential safety comparisons are reported in the registry entries, so the adverse-event counts are descriptive rather than a complete analysis of between-group uncertainty.

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

The registry record establishes that a randomized, placebo-controlled phase 2 trial evaluated a two-injection chikungunya virus-like particle vaccine in healthy adults. It specifies the primary local-reactogenicity endpoint, its reporting window, and the general method used to record symptoms. It also provides selected adverse-event counts and identifies neutralizing antibody geometric mean titers as secondary outcomes.

Those details do not establish a complete result for the primary endpoint. The endpoint includes multiple categories and time points, and no single comparison is reported. The record therefore does not allow a precise description of the vaccine-versus-placebo difference in local symptoms, or of the uncertainty around such a difference. The numerical antibody results are also not reported in the registry record.

The safety counts should not be interpreted as proof that an intervention caused or prevented any event. They are descriptive participant counts, and the serious-event terms carry no reported attribution. A causal interpretation would require a clearly defined analysis and consideration of the trial’s data and methods, not just a comparison of counts.

This trial record also does not answer whether vaccination prevents chikungunya infection or changes clinical outcomes from infection. The listed outcomes concern safety and antibody titers, and no clinical-protection result is stated. Nor does the record describe the statistical plan, sample-size justification, interim analyses, or the full treatment of missing data. Those topics are not reported in the registry record and should not be filled in by assumption.

The most defensible conclusion is limited: the trial design and several descriptive safety figures are available, while the principal outcome comparison and antibody results needed for a fuller statistical interpretation are absent from the record. This is a statement about the information recorded, not a medical recommendation or a conclusion that the intervention is effective or ineffective.

13. Why This Trial Matters Statistically

This trial illustrates why a clearly described endpoint is not the same as a fully interpretable result. The registry defines the primary outcome in operational terms: participants recorded solicited local symptoms, symptoms were reviewed with clinic staff, and each symptom was counted at its worst severity. Such detail helps readers understand what the count is intended to represent.

At the same time, the endpoint has multiple categories and severity levels. The registry does not reduce it to one comparison, so readers cannot derive a single estimate of the primary outcome contrast from the record. This is a useful statistical distinction: an endpoint can be carefully specified while its group-level results and uncertainty remain unavailable.

The record also illustrates the need to distinguish descriptive safety counts from estimates designed for inference. Counts of serious and other adverse events can convey what was recorded in each group, but without a reported analysis they do not supply a confidence interval, a formal comparison, or a causal explanation. The serious-event terms are presented without attribution, making that distinction especially important.

Finally, analysis populations and missing observations are part of the evidence, not administrative details. The antibody outcomes are named for three populations, but their definitions and results are not reported in the registry record. The primary safety description notes participants who did not receive product or lacked a diary card, but does not explain the full handling of missing reports. These gaps show why complete outcome reporting and transparent statistical methods are necessary for readers to judge precision, robustness, and the scope of conclusions.

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 primary limitation for statistical interpretation is that the primary endpoint is not reported as a single comparison. Its definition covers several symptom categories and severity levels, but the available record does not provide the corresponding category-specific results. No primary effect estimate, confidence interval, or p-value is stated. The endpoint’s design can therefore be described, but its between-group result cannot be quantified.

The secondary neutralizing antibody outcomes are listed for per-protocol, intent-to-treat, and modified intent-to-treat populations, but no numerical results or detailed population definitions are reported in the registry record. The registry lists 9 outcome measures overall and 0 analyses, leaving no analysis-level antibody estimates for interpretation.

The safety information is also limited. Serious and other adverse-event counts and selected serious-event terms are present, but the record does not give causal attribution, a complete inferential comparison, or details about event coding and overlap. The primary endpoint description notes four participants in Group 1 who did not receive product and one in Group 2 who did not provide a diary card following the first injection; handling of all missing safety data is not described.

The registry record does not report a statistical analysis plan, the trial’s sample-size justification, interim analyses, multiplicity procedures, or model details. It also does not give details about the masking roles or the full definitions of all analysis populations. These limitations are specific to what is reported for this trial and constrain how far conclusions can be taken from the posted information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Trial for Safety and Immunogenicity of a Chikungunya Vaccine, VRC-CHKVLP059-00-VP, in Healthy Adults — NCT02562482.
• Registry record last updated 2020-10-22; status last verified 2020-10.
• Results first posted 2019-05-14.
• 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

NCT02562482 is a completed phase 2 randomized, placebo-controlled, parallel-group trial of a chikungunya virus-like particle vaccine in healthy adults. The registry records enrollment of 400, a start date of 2015-11-18, and a primary completion date of 2018-03-06. The vaccine group was assigned two intramuscular injections of VRC-CHKVLP059-00-VP at 20 micrograms; the comparator group was assigned two injections of phosphate buffered saline placebo.

The primary outcome was the number of participants reporting local reactogenicity signs and symptoms within 7 days of any injection. The record describes symptom collection and grading but does not report one primary comparison. It lists neutralizing antibody geometric mean titers as secondary outcomes in three analysis populations, without numerical results in the information.

Recorded serious adverse events affected 4 of 197 participants in the vaccine group and 11 of 198 in the placebo group; other adverse events affected 123 of 197 and 128 of 198. The record lists 0 deaths in each group. Statistical analysis details, the trial’s sample-size justification, and the full handling of missing data are not reported in the registry record.