Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004) (NCT02314923), a randomized phase 1 study. The primary outcome is Percentage of Participants With One or More Solicited Injection-site Adverse Events by Severity.

2. Clinical Question

3. Trial Design

This was a phase one, randomized, parallel-group, placebo-controlled study with triple masking. The official title describes it as multicenter and double-blind; the registry's masking field says triple. The study is listed as completed, with enrollment of 513. Its stated purpose was to evaluate safety and immunogenicity of the V920 Ebola vaccine candidate in healthy adults.

Participants were assigned to dose cohorts of V920 or to placebo. The listed vaccine doses include 3x10^3 pfu, 3x10^4 pfu, 3x10^5 pfu, 3x10^6 pfu, 9x10^6 pfu, 2x10^7 pfu, and 1x10^8 pfu. Cohort 1 includes the lower dose groups and placebo; cohort 2 includes further dose groups and placebo. However, the cohort 2 arm named 3x10^6 pfu is described as receiving 3x10^3 pfu. The record does not resolve this inconsistency.

The primary endpoint concerns solicited injection-site adverse events through 14 days postvaccination. The registry specifies erythema, pain, tenderness, and swelling as prompted symptoms, and says severity was graded by the investigator. Secondary outcomes include mean vector RNA copies for participants with a V920 PCR result at or above the lower limit of quantification, and percentages with seroconversion for ZEBOV-specific IgG and ZEBOV neutralizing antibodies. The record does not report the full schedule of assessments or the statistical analysis plan.

The study start date is 2014-12-05, and primary completion is recorded as 2016-06-23. These dates describe the registry timeline; they do not by themselves establish when each participant was assessed or how long each outcome was followed.

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.

Only the first 6 of 10 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All randomized participants who received study vaccination and had data available for the endpoint.

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: Baseline characteristics were reported for treated participants. 1 participant in 9x10\^6 pfu V920: Cohort 2 arm did not receive vaccine

Only the first 6 of 11 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With One or More Solicited Injection-site Adverse Events by Severity, measured over Up to 14 days postvaccination.

The primary endpoint is the percentage of participants with one or more solicited injection-site adverse events, grouped by severity, up to 14 days after vaccination. The registry defines an adverse event broadly as an unfavorable or unintended sign, symptom, or disease temporally associated with the study vaccine or a protocol-specified procedure, whether or not judged related. Worsening of a preexisting condition is included when temporally associated.

For this endpoint, participants were prompted to report erythema, pain, tenderness, and swelling on a Vaccination Report Card. Investigators graded reported events using a toxicity grading scale based on FDA guidance for healthy adult and adolescent volunteers in preventive vaccine trials. The registry describes Grade 1 as mild, Grade 2 as moderate, Grade 3 as severe, and Grade 4 as potentially life-threatening.

A participant-level percentage is useful for describing how commonly participants experienced at least one event in each severity category. It differs from an event count, because one participant can experience multiple symptoms. Comparing dose groups with placebo can describe the observed pattern across randomized groups, but interpretation requires the group estimates and their uncertainty. Those primary endpoint results are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The outcome is a binary participant-level measure within severity categories: whether a participant experienced at least one solicited injection-site adverse event of the specified grade during the stated follow-up period. A percentage expresses the share of participants meeting that definition. This is different from counting every symptom, since an individual participant may report more than one symptom. The registry says the percentages were summarized by grade, but does not report the actual endpoint estimates.

What does a confidence interval describe?

In general, a confidence interval describes the statistical uncertainty around an estimate under a specified analysis. For a percentage, it helps indicate how compatible the observed data are with a range of underlying event frequencies. Narrower intervals generally indicate greater precision, while wider intervals indicate less precision. A confidence interval is not a guarantee that the true value lies within its limits, and it does not by itself establish whether a difference is important. No confidence intervals for the primary endpoint are reported in the registry record.

How should vaccine and placebo groups be compared?

In general, a randomized comparison can estimate how outcomes differed between assigned groups, provided the analysis population and outcome definitions are clearly specified. For a binary endpoint, one may compare the group percentages or an effect measure based on those percentages. The choice of effect measure affects interpretation: an absolute difference describes a change in percentage points, while a relative measure describes a proportional contrast. No such primary endpoint comparisons are available in the registry record, so no effect estimate should be inferred from the study design alone.

The trial includes several V920 dose cohorts and two placebo cohorts. A dose-response question would examine whether the observed endpoint varies across dose levels, but the registry record does not give the primary outcome results needed to assess such a pattern. In addition, the cohort 2 arm named 3x10^6 pfu is described in its arm text as receiving 3x10^3 pfu. That mismatch makes the stated dose for that arm uncertain in the record and should be resolved before interpreting any dose-based comparison.

What do the safety counts mean?

The serious adverse event figures are counts of affected participants with group-specific participants at risk. Counts retain useful detail, especially when outcomes are uncommon, but they do not convey precision on their own. In general, estimates based on fewer participants tend to be less precise than those based on more participants. The group sizes in this study's safety summaries are not identical, so raw event counts should not be compared as though the groups had equal denominators. The record does not provide confidence intervals for these safety results.

The separate count of participants with other adverse events should not be conflated with the primary endpoint. The primary endpoint is restricted to solicited injection-site events through 14 days and summarized by investigator-assessed grade. The record's safety summary also includes broader categories. Without definitions of every safety-summary category and corresponding analysis details, their relation to the primary endpoint cannot be assumed.

What does a sample-size illustration represent?

In general, a planning illustration estimates the sample size that might be needed under stated assumptions. The registry's stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect defined as a stated fraction of the observed effect. Such an illustration is not the trial's original design justification and is not evidence about the probability that the completed trial detected an effect. The record does not report the trial's own sample-size justification. Planning figures should not be described as observed power.

The registry's primary endpoint population is all randomized participants who received study vaccination and had endpoint data available. This definition excludes randomized participants without vaccination or without available endpoint data from that endpoint summary. The number of participants meeting this definition in each dose group is not reported in the registry record. The registry also lists nine outcome measures and 35 analyses, but the detailed statistical methods, prespecified comparisons, and analysis populations for all outcomes are not reported.

10. Multiplicity, Missing Data and Analysis Populations

The study includes multiple vaccine doses, two placebo cohorts, a primary endpoint summarized by severity, and secondary immunogenicity outcomes. When many outcomes, dose groups, severity categories, or comparisons are examined, the chance of finding an apparently notable result by chance can increase. General approaches include prespecifying a limited set of comparisons or adjusting the interpretation or testing procedure for multiple comparisons. The registry record does not report whether multiplicity was addressed, which comparisons were prespecified, or how the 35 listed analyses relate to the outcomes.

Missing outcome data can affect both the estimated percentages and the groups represented in an analysis. The registry defines the primary endpoint population as randomized participants who received study vaccination and had data available for the endpoint. This is a post-randomization subset, rather than all randomized participants. The number excluded because of missing endpoint data, reasons for missingness, and any method used to address missing data are not reported in the registry record.

The record does not report an intention-to-treat analysis population for the primary endpoint, nor does it describe sensitivity analyses for missing observations. It also does not state how participants with incomplete follow-up, ambiguous event reports, or missing severity grades were handled. These details matter because the primary outcome is a participant percentage, and its denominator depends on the analysis population and data availability.

The registry lists 513 enrolled participants, but enrollment alone does not identify the number contributing to every endpoint or analysis. Group-specific primary endpoint denominators are not reported in the registry record. The interpretation of any posted result should therefore rely on its stated analysis population and denominators, rather than assuming that all enrolled participants contributed to every analysis.

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: chest pain (1.6%), head injury (1.6%), presyncope (1.6%), ulna fracture (1.4%), peripheral ischaemia (1.4%).

The registry lists serious adverse event counts by group, alongside the number of participants at risk. The counts are 0 of 64 for 3x10^3 pfu V920 cohort 1, 0 of 64 for 3x10^4 pfu V920 cohort 1, 1 of 64 for 3x10^5 pfu V920 cohort 1, and 2 of 64 for 3x10^6 pfu V920 cohort 1. Placebo cohort 1 has 1 of 74. In cohort 2, the counts are 0 of 20 for the arm named 3x10^6 pfu, 0 of 47 for 9x10^6 pfu, 0 of 47 for 2x10^7 pfu, 0 of 48 for 1x10^8 pfu, and 0 of 20 for placebo.

These are observed participant counts, not estimates of comparative risk. The cohort 2 3x10^6 pfu arm has a conflicting dose description in the record, and should be interpreted cautiously by dose. The registry also reports one death in the 3x10^6 pfu V920 cohort 1 group; it does not state the cause or relationship to vaccination. The serious-event counts do not establish causation. The record does not report confidence intervals or adjusted comparisons for these safety figures.

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

The registry record describes a randomized, placebo-controlled phase one study of V920 in healthy adults, with multiple dose cohorts and safety and immunogenicity objectives. It provides a clear definition of the primary solicited injection-site endpoint and reports some safety counts. The primary endpoint was intended to describe the percentage of participants experiencing at least one injection-site event by severity up to 14 days after vaccination.

However, the primary endpoint results themselves are not reported in the registry record. There are no percentages by severity, no endpoint denominators by group, and no confidence intervals or comparative estimates in the record. Consequently, the endpoint's observed frequency and its pattern across doses and placebo cannot be evaluated from these registry entries. The study's design does not substitute for the missing outcome estimates.

The serious adverse event summaries show few affected participants in the listed groups, with the counts varying across groups. These descriptive counts do not establish that vaccination caused or did not cause an event. The listed death is not accompanied by a cause or attribution. The serious adverse event term percentages also lack denominator and group-level context in the registry information.

These results do not establish the vaccine's efficacy against Ebola. The stated primary endpoint is a short-term safety measure, and the secondary outcomes concern vector RNA and antibody seroconversion. The registry record does not report clinical protection outcomes, nor does it provide the immunogenicity results in the registry record described. No conclusion about protective benefit follows from the endpoint definitions or safety counts alone.

The conclusions that can be drawn are therefore limited to what the record documents: the trial's randomized parallel-group structure, the dose cohorts and placebo groups, the endpoint definitions, and the reported safety counts. Interpretations of endpoint effects, dose response, causality, and precision require outcome estimates and analysis details not reported in the registry record.

13. Why This Trial Matters Statistically

This trial illustrates why a study's design and its outcome reporting need to be considered separately. Randomization, placebo groups, masking, and multiple dose cohorts describe how the study was structured. They do not reveal the size or precision of an endpoint effect. In this case, the registry defines the primary safety outcome but does not report its results by severity.

The endpoint also demonstrates the importance of distinguishing participant-level percentages from event counts. A participant with several prompted symptoms may still count once for a category defined as one or more events. Clear definitions of the event, severity grading, follow-up period, and analysis population are essential for interpreting a percentage. The record includes those elements in part, but omits group-specific endpoint estimates and denominators.

Safety summaries need the same care. Group sizes differ, and sparse event counts can be difficult to compare without uncertainty estimates. The reported serious adverse events and death should be read descriptively; the record does not provide the information needed to infer causation or make precise comparisons.

The record also contains a mismatch between the cohort 2 arm name 3x10^6 pfu and its description of 3x10^3 pfu. This is a practical example of why arm labels and intervention descriptions need to agree before interpreting dose-response patterns. More broadly, the registry does not report the multiplicity strategy, missing-data handling, or full analysis plan. These omissions limit how far statistical interpretation can go, even when the broad study design is documented.

14. Limitations

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

The main limitation for interpreting the primary endpoint is that its results are not reported in the registry record. The definition, follow-up period, and severity grading are described, but the percentages, group denominators, and uncertainty estimates are absent. This prevents assessment of the endpoint's frequency or comparisons across vaccine dose groups and placebo.

The record gives a total enrollment of 513, but does not identify the number contributing to each primary endpoint analysis. It defines the endpoint population as randomized participants who received vaccination and had endpoint data available. How many participants did not meet that definition, and why, are not reported. Missing-data handling and sensitivity analyses are also not described.

There is an inconsistency in the cohort 2 arm named 3x10^6 pfu: its description states that participants received 3x10^3 pfu. The record does not resolve which dose was administered. This limits dose-specific interpretation for that arm.

Although the registry lists serious adverse event counts, it does not provide confidence intervals or adjusted comparisons for them. The cause and relationship to vaccination for the recorded death are not stated. The term-level serious adverse event percentages are reported without the denominator details needed to assess their precision or compare groups.

The statistical analysis plan, including any multiplicity approach and the prespecified comparisons among several dose groups, is not reported in the registry record. The record also does not report the trial's sample-size justification. These gaps, along with the absence of primary endpoint estimates, limit conclusions about the strength and precision of the evidence.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Placebo Controlled, Dose Response, Safety and Immunogenicity Study of Vesicular Stomatitis Virus (VSV) Ebola Vaccine in Healthy Adults (V920-004) — NCT02314923.
• Registry record last updated 2020-02-05; status last verified 2020-01.
• Results first posted 2020-01-02.
• 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

NCT02314923 is a completed, randomized, parallel-group, placebo-controlled phase one study of the V920 Ebola vaccine candidate in healthy adults. The registry reports triple masking, enrollment of 513, a study start date of 2014-12-05, and primary completion on 2016-06-23. Multiple vaccine dose cohorts and placebo groups are listed.

The primary outcome is the percentage of participants experiencing one or more solicited injection-site adverse events by severity up to 14 days postvaccination. The registry defines the symptoms and grading approach but does not report primary endpoint results. Serious adverse event counts and a death are listed, without causal attribution or confidence intervals. The cohort 2 arm named 3x10^6 pfu has a description stating 3x10^3 pfu, an inconsistency the record does not resolve.