Ebola Sudan Chimpanzee Adenovirus Vector Vaccine in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Ebola Sudan Chimpanzee Adenovirus Vector Vaccine in Healthy Adults (NCT04041570), a non-randomized phase 1 study. The primary outcome is Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration.

2. Clinical Question

The primary endpoint focuses on local symptoms after vaccination rather than on antibody or T-cell responses. Participants recorded solicited symptoms on diary cards for 7 days after administration, then reviewed those records with clinic staff at a follow-up visit. For each symptom, a participant was counted once at the worst severity reported during the period, even if that symptom occurred more than once or at more than one severity.

This is a descriptive safety question in an early-phase dose-escalation study. It asks what was reported in the treated groups, not whether vaccination reduced disease risk or whether one dose is superior. Because allocation was non-randomized and the study had no masking, differences between groups, if reported, would need to be interpreted in light of the sequential design and the absence of a randomized control. Numerical primary-endpoint results are not reported in the registry record. The secondary outcomes concern antibody titers, positive Ebola-specific antibody responses, and T-cell responses; their numerical results are not reported in the registry record either.

3. Trial Design

NCT04041570 is a completed Phase I, open-label, dose-escalation clinical trial of cAd3-EBO S in healthy adults. The registry describes a sequential, non-randomized design with no masking. The study evaluated safety, tolerability, and immunogenicity after administration of two doses of the investigational vaccine. The vaccine is described as a chimpanzee adenovirus serotype 3 vector encoding wild type glycoprotein from the Sudan strain of Ebolavirus, administered intramuscularly.

The two study groups received different dose levels: Group 1 received 1x10^10 PU and Group 2 received 1x10^11 PU. Each group description specifies administration by needle and syringe in a volume of 1 mL. The registry lists enrollment of 40. The group descriptions list 20 participants at risk in each group for the adverse-event summaries. These details describe the record; the study was not randomized, and the groups should not be read as randomized treatment arms.

The primary outcome was the number of participants reporting local reactogenicity signs and symptoms during the 7 days after vaccine administration. The symptom-monitoring plan used participant diary cards and follow-up review with clinic staff. Severity grading followed the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine Clinical Trials, modified from FDA Guidance - September 2007.

Secondary outcomes listed in the registry address antibodies to the cAd3 vector, Ebola-specific antibody responses, baseline-subtracted antibody titers, positive Ebola-specific T-cell responses, and the magnitude of the Ebola Sudan-specific T-cell subset response. The record lists 11 outcome measures and 1 analysis, but the statistical analysis details are not reported in the registry record. The record also does not report a randomized comparator, a masking procedure, or a separate protocol-based sample-size justification. The trial dates are listed as 2019-07-02 for start and 2020-09-07 for primary completion.

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: All participants who received the cAd3-EBO S vaccine.

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 participants.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Local Reactogenicity Signs and Symptoms for 7 Days After the cAd3-EBO S Vaccine Administration, measured over 7 days after study product administration.

The primary endpoint counts participants who reported local reactogenicity signs and symptoms during the 7 days after cAd3-EBO S administration. Participants recorded solicited symptoms on diary cards for that period and reviewed the cards with clinic staff at a follow-up visit. A participant was counted once for each symptom, using the worst severity reported if the symptom occurred repeatedly or at different severities. The endpoint also includes a count for any local symptom at the participant’s worst severity.

The registry describes grading as mild, moderate, or severe, using a toxicity grading scale modified from FDA guidance. The endpoint is therefore a participant-level description of reported local symptoms and their severity, not a count of every symptom episode. This distinction matters: repeated reports of the same symptom from one participant do not translate into multiple participants in the endpoint count.

In general, solicited reactogenicity outcomes are used to characterize short-term symptoms that are specifically monitored after an intervention. They can make the safety profile more interpretable than an unspecific collection of events, because the symptoms and observation window are defined in advance in the outcome description. This endpoint does not by itself capture every possible adverse event or establish the cause of a reported symptom. Nor does a short, defined reporting window describe outcomes beyond that period.

The population specified for this measure is all participants who received the vaccine. However, numerical results for the primary endpoint are not reported in the registry record. The registry record therefore gives the measurement approach and timeframe, but not the group-specific participant counts or severity results needed to describe the observed local-reactogenicity findings.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary measure is a count of participants reporting symptoms, not a count of every symptom occurrence. Under the registry definition, each participant is counted once for each symptom at the worst severity they reported during the 7-day observation period. The separate “Any Local Symptom” measure counts participants reporting any local symptom at their worst severity. This definition prevents repeated occurrences of the same symptom in one person from being mistaken for multiple people with that symptom.

In general, participant counts are useful for describing how widely an event was reported within a defined group. They are not the same as event rates over person-time, because the measure does not describe person-time accumulation. They are also distinct from a severity score averaged across participants. To interpret a count fully, a reader needs the relevant denominator, eligibility for the measure, event definition, and observation window. The primary outcome description specifies the population as participants who received the vaccine and gives the observation window, but numerical primary outcome counts are not reported in the registry record.

Why does design affect interpretation?

The study is described as non-randomized and sequential, with no masking. Random allocation is one way trials make measured and unmeasured baseline characteristics more comparable across groups on average. Without random allocation, a difference between sequential dose groups cannot automatically be attributed to dose alone. The record does not report the sequence-specific enrollment details or an adjusted comparison that could address possible group differences.

Open-label means the study is described as having no masking. In general, knowledge of the assigned intervention can influence symptom perception, reporting, follow-up, or assessment. That does not show that reporting was biased in this trial; it identifies a possibility relevant to how subjective symptom outcomes are interpreted. Solicited diary-card recording gives a defined way to collect reports, but does not by itself eliminate reporting effects.

A dose-escalation design studies successive dose levels, but the registry record does not report the detailed escalation rules or the decision criteria used between groups. Those details are not reported in the registry record. The design label alone should not be used to infer a particular stopping rule, safety review process, or protocol schedule.

What do estimates and confidence intervals mean?

In general, an estimate summarizes the observed data using a chosen statistical quantity, such as a proportion or a difference between groups. A confidence interval describes uncertainty in an estimate under the assumptions of the method used. A wider interval indicates less precision than a narrower interval, but interval width is not a measure of clinical importance. An interval also does not correct for limitations in study design, outcome ascertainment, missing observations, or selective reporting.

For a binary outcome, a model might estimate a proportion of participants with an event. A comparison might then be expressed as an absolute difference or another contrast, but the choice should match the question and analysis plan. These are general statistical possibilities, not reported analyses for this trial. The registry record does not report the primary endpoint’s numerical group results, confidence intervals, p-values, or a detailed statistical model. It would therefore be inappropriate to present an estimated contrast or its precision.

The adverse-event entries are counts with denominators, not adjusted comparative estimates. In general, comparing crude proportions across non-randomized groups can be misleading if groups differ in composition, follow-up, or ascertainment. No adjustment procedure is described in the registry record, so the adverse-event counts should remain descriptive.

How should sample-size planning be understood?

In general, a sample-size calculation is a planning exercise based on assumptions about a target effect, variability, significance level, power, allocation, and analysis method. It does not describe what was observed in a completed trial. A planned sample size is not “observed power,” and a planning illustration based on an observed effect does not make that effect reliably detectable in future studies without considering uncertainty and design differences.

The registry information describes planning illustrations based on an observed effect, using a two-sided significance level of 0.05, equal allocation, and a normal approximation; the stated effect to detect is a fraction of the observed effect. These illustrations are not identified as the trial’s own design justification. The actual illustration values are not reported in the registry record in the information available for this analysis, so no target group size should be inferred from them. The record also does not report a protocol-based sample-size rationale.

What is not specified?

Although the record lists 11 outcome measures and 1 analysis, the analysis methods are not detailed. The statistical plan, handling of missing outcomes, treatment of multiple outcomes, and any interim analyses are not reported in the registry record. These omissions matter because the method chosen can influence estimates and uncertainty, while selective availability of results can make a record appear more complete than it is. A sound reading separates what the outcome definitions specify from what the registry does not document.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary local-reactogenicity outcome and secondary antibody and T-cell measures. It lists 1 analysis, but does not provide a detailed statistical analysis plan. The method for controlling or interpreting multiplicity across outcomes is not reported in the registry record. In general, testing multiple outcomes can increase the chance of at least one apparently unusual result when each test is considered separately. Whether and how that issue should be addressed depends on the prespecified analysis strategy and the role assigned to each outcome; neither is described in enough detail in the registry record to characterize the approach.

Missing-data handling is also not reported in the registry record. The primary outcome population is described as all participants who received the vaccine, but the record does not state how missing diary cards, incomplete symptom reports, missed follow-up, or unavailable laboratory measurements were handled. The reported population definition should not be taken as evidence that every participant posted complete observations for every outcome.

The record does not report an analysis population for the secondary immunogenicity outcomes or explain whether those analyses used all vaccine recipients, a subset with available samples, or another rule. No imputation method, sensitivity analysis, or missingness assessment is described. These details are important because missing observations can affect both the number analyzed and how representative the observed results are.

Numerical primary outcome results and secondary immune-response results are not reported in the registry record. As a result, multiplicity adjustments and missing-data procedures cannot be assessed from the recorded information. The registry’s listing of outcome measures identifies planned or registered questions, but does not substitute for a report of estimates, denominators, analysis populations, and methods.

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 non-serious adverse event terms

The adverse-event summary lists serious adverse events and other adverse events separately for the two dose groups. Group 1 lists 20 participants at risk for serious adverse events, with 0 affected, and 20 at risk for other adverse events, with 19 affected. Group 2 also lists 20 at risk for serious adverse events, with 0 affected, and 20 at risk for other adverse events, with 19 affected. Deaths are listed as 0 in both groups. The registry does not list serious adverse-event terms.

These entries are descriptive counts, not proof that an event could never occur or that the risk is absent. In general, a count of zero in a study group can coexist with substantial uncertainty about the frequency of uncommon events, especially when the group is limited in size. The record does not provide confidence intervals for these adverse-event counts.

The “other adverse events” category is not defined further in the available registry information, so it should not be equated with the solicited local-reactogenicity endpoint. That endpoint has its own symptom list, severity rules, and 7-day reporting period. The registry record does not state that the adverse-event summary uses the same event definitions or observation window. These counts therefore should be read according to their listed categories, without inferring more detail than the record reports.

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

The record documents a Phase I investigation of two cAd3-EBO S dose levels in healthy adults, with a focus on safety, tolerability, and immunogenicity. It specifies the route and volume of administration, the sequential non-randomized design, and the method for recording solicited local symptoms during the 7 days after administration. It also provides adverse-event summary counts by group.

For the adverse-event categories reported, the registry lists 0 participants with serious adverse events in each group and 19 participants with other adverse events in each group. It lists 0 deaths in both groups. These figures describe what the registry record reports; they do not establish that there was no risk of serious events, nor do they characterize the nature, timing, severity, or duration of the other adverse events. The record does not list serious adverse-event terms.

The primary endpoint is clearly defined, but its numerical results are not reported in the registry record. The record therefore does not support a numerical conclusion about the frequency or severity of local symptoms. Nor do the listed immune-response outcomes, without numerical results, establish the size or precision of antibody or T-cell responses.

This study does not provide a randomized comparison with placebo or another control. Its sequential dose groups cannot be treated as equivalent groups differing only in dose. The data recorded cannot establish comparative efficacy, prevention of Ebola, or the clinical importance of any immune response. The trial’s completed status is a registry status, not a substitute for unreported outcome results.

In general, early-phase trials can describe outcomes observed in a defined study setting and help frame questions for further research. Their interpretation depends on design, sample size, outcome completeness, follow-up, and precision. In this case, the available registry record supports a description of the design and selected adverse-event counts, while leaving the primary outcome results, immune-response estimates, and detailed analysis methods unreported.

13. Why This Trial Matters Statistically

This trial is statistically instructive because it combines a clearly defined short-term symptom outcome with a non-randomized, sequential dose-escalation design. The symptom endpoint counts people rather than repeated symptom episodes and applies a worst-severity rule. Those definitions determine what the resulting count would mean and prevent it from being confused with an event total or a severity average.

The study also illustrates why design labels matter. A comparison between groups is not automatically causal simply because the groups received different doses. Randomization and masking address different sources of bias; neither is present according to the registry description. Sequential enrollment further means the groups are not a randomized, concurrent control comparison. Any numerical contrast, if one were available, would require cautious interpretation.

The registry’s adverse-event summaries show why counts should be read alongside their denominators and event categories. The same number of affected participants can have different meanings under different definitions, follow-up periods, or ascertainment procedures. Here, the primary solicited local-symptom outcome and the broader adverse-event categories are separately described, and the registry record does not establish that they share definitions or windows.

The record also demonstrates a reporting distinction: outcome definitions can be detailed even when numerical outcome results are absent. A precise endpoint description does not permit reconstruction of the observed result. Likewise, a completed trial status does not show that each registered outcome has a posted estimate. For statistical interpretation, the difference between a registered measure and a reported analysis is essential.

Finally, planning calculations and observed results answer different questions. A planning illustration based on an observed effect is not the trial’s sample-size justification and should not be called observed power. Keeping planning assumptions separate from outcome evidence avoids overstating what the design or the recorded results can 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 main limitation for interpreting the primary question is that numerical local-reactogenicity results are not reported in the registry record. The endpoint definition and reporting period are available, but group-specific symptom counts and severity distributions are not. This prevents direct description of the primary findings and rules out a grounded statistical comparison on that outcome.

The study is listed as non-randomized, sequential, and open-label. There is no placebo or randomized control group described. Consequently, the design cannot isolate dose effects from other possible differences between groups, and symptom reports may be subject to the general limitations of unmasked ascertainment. The registry does not report adjustment methods or detailed information about the sequence of group enrollment.

The adverse-event summary is limited to counts and categories. The record does not provide event descriptions for the “other” category, detailed timing or duration, or confidence intervals. No serious adverse-event terms are listed. The summary therefore cannot convey the full clinical character or precision of those entries.

Numerical results for the secondary immunogenicity measures are not reported in the registry record. The detailed statistical analysis plan, multiplicity approach, missing-data handling, interim analyses, and sample-size justification are also not reported. It is therefore not possible to assess whether results were adjusted for multiple outcomes, how incomplete observations were treated, or how the trial’s planned size related to a prespecified target effect. These are limits of the registry information, not evidence that a particular method was or was not used outside the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Ebola Sudan Chimpanzee Adenovirus Vector Vaccine in Healthy Adults — NCT04041570.
• Registry record last updated 2022-12-06; status last verified 2022-11.
• Results first posted 2021-11-24.
• 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.

18. Record Summary

NCT04041570 is a completed Phase I, open-label, non-randomized, sequential dose-escalation trial of cAd3-EBO S in healthy adults. The registry lists enrollment of 40 and two intramuscular dose groups: 1x10^10 PU and 1x10^11 PU. The primary endpoint counts participants reporting local reactogenicity symptoms during the 7 days after administration, using the worst reported severity for each symptom.

Numerical primary-endpoint and immunogenicity results are not reported in the registry record. The adverse-event summary lists 0 serious adverse events and 0 deaths in each group; it lists 19 participants with other adverse events in each group. The record does not provide a detailed statistical analysis plan, missing-data procedures, or a protocol-based sample-size justification. The design and reported counts support descriptive reading, not a randomized dose comparison or a conclusion about vaccine efficacy.