COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral Platform in Healthy South African Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral Platform in Healthy South African Adults (NCT04710303), a non-randomized phase 1 study. The primary outcome is Number of Participants With Medically Attended Adverse Events (MAAE).

2. Clinical Question

The central statistical question is descriptive: what safety information does the registry record report for participants receiving the study vaccine, and how much can that information establish about differences between regimens? The design can describe events recorded in the listed cohorts, but its non-randomized structure does not support a reliable causal comparison of doses. In addition, the registry record does not provide the primary endpoint result, immunogenicity estimates, or a complete account of the statistical analyses. This limits interpretation to the design details and the adverse-event counts that are posted.

3. Trial Design

NCT04710303 is a completed phase 1b study sponsored by ImmunityBio, Inc. The record gives a study start date of 2021-03-02 and a primary completion date of 2022-08-02. It describes the trial as open-label, non-randomized, and sequential. Participants and investigators were not masked to treatment, and there was no randomized allocation to a control regimen.

The intervention was hAd5-S-Fusion+N-ETSD. Cohort 1 was assigned 5 × 10e10 Viral Particles (VP) per dose on Days 1 and 22. Cohort 2 was assigned 1 × 10e11 VP per dose on Days 1 and 22. Cohort 3 was assigned 1 × 10e11 VP per dose, with 5 × 10e10 VP per dose as an alternative if safety concerns were identified at the higher dose, on Day 1. Cohort 6 was assigned 2 × 10e10 VP per nostril, or 4 × 10e10 VP per dose, on Day 1. The record does not explain why the cohort sequence omits other cohort numbers.

The planned focus was safety, reactogenicity, and immunogenicity, with dose selection for future studies as an objective. Follow-up for the primary endpoint differed by cohort: through 1 week after the final administration, up to 29 days for Cohorts 1 and 2 and up to 8 days for Cohorts 3 and 6. The registry record does not report a detailed protocol for how dose decisions were made, or how sequential enrollment was managed. The design is useful for describing early-stage experience with the regimens, but it does not create a randomized comparison between them.

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.

Population: All participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Medically Attended Adverse Events (MAAE), measured over From first dose of study treatment through 1 week post final vaccine administration; up to 29 days for Cohorts 1 and 2, and up to 8 days for Cohorts 3 and 6..

The primary endpoint is the number of participants with medically attended adverse events (MAAE). It counts participants who experienced an event meeting the endpoint definition, rather than the total number of events. The timeframe begins with the first dose and ends 1 week after the final vaccine administration. The record specifies a maximum timeframe of up to 29 days for Cohorts 1 and 2 and up to 8 days for Cohorts 3 and 6.

This kind of endpoint is used in safety assessment because it focuses on adverse events that led to medical attention during the specified follow-up period. It can help describe the frequency of clinically attended events in the study population. It does not, on its own, describe every symptom or reaction: events that did not receive medical attention may not meet this endpoint. The registry record does not provide further detail about the definition of medical attendance, event adjudication, or how events were attributed to the vaccine.

The endpoint is reported as a participant count. To interpret that count fully, readers would also need the number of participants assessed, the event definition, and the analysis population used. Although the registry record includes enrollment and separate safety counts, it does not report the primary MAAE result or an analysis population for that endpoint. Consequently, the primary safety outcome cannot be quantified from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count measure? The primary endpoint is a count of participants with at least one medically attended adverse event during the stated follow-up. This differs from an event count: one participant could experience more than one event, while the participant count would still count that person once. The registry record specifies the endpoint and its timeframe, but does not report the primary result or explain the detailed event definition.

Why does the denominator matter? A count is most interpretable alongside the number of participants assessed for the outcome. The denominator identifies the population at risk or analyzed, and helps readers understand how much observation supports the count. The adverse-event listings give group-specific denominators, but the primary MAAE denominator and analysis population are not reported in the registry record. The Cohort 2 denominator in the safety listings is 11, whereas its arm description states n = 10; the record does not explain the difference. These values should not be silently treated as interchangeable.

What does a confidence interval mean? In general, a confidence interval expresses the uncertainty around an estimated effect or event rate under a statistical model. A narrower interval indicates greater precision under that model, while a wider interval indicates less precision. It does not repair limitations in the study design, such as non-random allocation or incomplete reporting. The registry record does not report a confidence interval for the primary endpoint or other outcome estimates.

Can the cohorts be compared as treatment groups? The trial is non-randomized and sequential, not a randomized controlled comparison. In general, random allocation helps balance known and unknown participant characteristics between groups. Without randomization, differences between cohorts may reflect participant characteristics, timing, follow-up, or other factors as well as regimen. This matters particularly because the regimens vary in dose and schedule. The registry record does not report an adjusted comparative analysis, and its skip note cautions that the arms are not a like-for-like control comparison.

What does the planning illustration mean? A sample-size calculation is a planning exercise, not an observed trial result. The assumptions described for the planning illustration include a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration is expressed as participants per arm; time-to-event planning is expressed as a total number of events. These assumptions do not describe the actual trial design, which was non-randomized and sequential. The registry record does not report a sample-size justification used to design this trial, and planning figures must not be interpreted as observed power.

What is over-dispersion? In general, over-dispersion occurs when observed variability in count data is greater than a chosen model expects. Ignoring it can make uncertainty appear smaller than it is. The posted primary outcome is a participant count, but the registry record does not report a model, dispersion estimate, or analysis method for that endpoint. It is therefore not possible to say whether an over-dispersion adjustment was planned or used.

How should zero counts be read? In general, observing no events in a group does not prove the underlying event risk is zero. The interpretation depends on the number of people observed, the duration and completeness of follow-up, and the event definition. Here, the serious adverse-event count is zero in each listed group, but the record does not report a confidence interval or a detailed account of missing follow-up. These counts are descriptive and cannot establish that serious events are impossible.

What can be concluded when analyses are absent? The registry record reports no posted analyses. That means readers cannot inspect an estimated effect, uncertainty interval, hypothesis test, or adjustment for potential differences between cohorts. Absence of a reported analysis is not evidence that the endpoint had no events or that a comparison was not statistically significant. It means the registry record does not report those results.

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("Cohort 1 (n = 10): hAd5-S-Fusion+N-ETSD at 5 × 10e", "Cohort 2 (n = 11): hAd5-S-Fusion+N-ETSD at 1 × 10e", "Cohort 3 (n = 10): hAd5-S-Fusion+N-ETSD at 1 × 10e", "Cohort 6 (n=10):hAd5-S-Fusion+N-ETSD at 4 × 10e10 ")
n      <- c(10, 11, 10, 10)
events <- c(0, 0, 0, 1)
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  Cohort 1 (n = 10): hAd5-S-Fusion+N-ETSD at 5 × 10e  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  Cohort 2 (n = 11): hAd5-S-Fusion+N-ETSD at 1 × 10e  11  0  0.0  0.0  28.5  -0.0  25.9  0.2  26.5
ARM  Cohort 3 (n = 10): hAd5-S-Fusion+N-ETSD at 1 × 10e  10  0  0.0  0.0  30.8  0.0  27.8  0.2  28.5
ARM  Cohort 6 (n=10):hAd5-S-Fusion+N-ETSD at 4 × 10e10   10  1  10.0  0.3  44.5  1.8  40.4  2.3  41.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists eight outcome measures, but it does not report a statistical analysis plan describing how multiple outcomes were handled. When a study examines several outcomes or makes several comparisons, the chance of obtaining an apparently notable result by chance can increase. In general, multiplicity procedures can address that issue, but their choice depends on the study questions and analysis plan. No multiplicity adjustment or hierarchy of confirmatory outcomes is reported in the registry record.

The record names a primary safety endpoint, but does not report its result or an analysis population. It also does not report whether the other outcome measures were treated as exploratory, how many comparisons were planned, or whether any interim analyses were conducted. Interim analyses are not reported in the registry record. The absence of this information means that the status and interpretation of any unposted tests cannot be assessed.

Missing-data procedures are also not reported in the registry record. It does not describe how participants with incomplete follow-up, unavailable measurements, or missed assessments were handled, nor does it say whether imputation or sensitivity analyses were planned. This is relevant because the endpoint has a defined follow-up period and the duration varies between cohorts. The record does not provide the number of participants with complete endpoint data.

Analysis populations are not reported in the registry record. It is therefore unclear whether endpoint summaries were intended for all enrolled participants, those who received a dose, or another specified group. These are important distinctions for safety and immunogenicity outcomes. No analysis results are posted, so there is no basis for judging whether missing data, multiple outcomes, or analysis population choices affected reported estimates.

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

The safety listings show zero participants with serious adverse events in each of the listed groups. Each listing gives a group-specific number at risk, with 10 for Cohorts 1, 3, and 6 and 11 for Cohort 2. No serious-event terms are listed in the registry record. These are descriptive entries; they do not establish that serious events cannot occur or provide a precise estimate of risk.

The record also gives counts of participants affected by other events. Those counts should not be read as the primary MAAE result: the record does not define them as medically attended events or provide enough detail to map them to that endpoint. The group labels Group 1 through Group 4 are not explained in the registry record, so their relationship to time points or other groupings cannot be inferred.

The registry record does not explain why the Cohort 2 safety denominator is 11 when its arm description states n = 10. It also does not report missing safety observations, completeness of follow-up, or uncertainty intervals for these counts. The serious-event entries should therefore be read as the recorded counts for the listed groups, not as a comprehensive estimate of safety or a comparison between regimens.

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

The record establishes that a completed phase 1b, open-label, non-randomized study evaluated hAd5-S-Fusion+N-ETSD in healthy South African adults. It describes the vaccine schedules and identifies safety, reactogenicity, and immunogenicity as study aims. Its primary endpoint was medically attended adverse events over a specified follow-up period, with different maximum follow-up durations for different cohorts.

The posted serious adverse-event counts are zero in each listed group. That is a descriptive observation within the registry’s safety listings. It is not a guarantee of no serious risk, and it does not quantify the primary MAAE endpoint. The primary endpoint result, immunogenicity results, and statistical analyses are not reported in the registry record. Accordingly, the record does not support a quantitative conclusion about the primary outcome or its precision.

The trial does not establish whether one regimen is safer or more immunogenic than another. Sequential non-randomized cohorts can differ for reasons other than dose, and their schedules and follow-up periods are not identical. Nor does this study establish whether the vaccine prevents COVID-19: the registry record does not report a randomized efficacy comparison or a clinical protection result.

The study objective included selecting a dose for future studies, but the registry record does not report the selection decision or the criteria used. It therefore cannot show which dose was selected or why. The results that are posted are best understood as limited descriptive safety information, rather than a definitive comparison or an estimate of clinical benefit.

14. Why This Trial Matters Statistically

This trial illustrates how early-phase studies can investigate a vaccine platform and multiple regimens before later research. The registry record describes several dose and administration schedules, a safety-focused primary endpoint, and additional aims involving reactogenicity and immunogenicity. Such studies can help characterize what was observed in an initial clinical setting and inform questions for subsequent research.

It also illustrates why design and reporting details matter to statistical interpretation. The trial is sequential and non-randomized, so cohort comparisons are not protected by random allocation. Different schedules and follow-up durations complicate comparisons further. The discrepancy between the Cohort 2 arm description and its safety denominator is another reason to read group counts alongside the record’s definitions rather than treating them as directly interchangeable.

Most importantly, the registry record does not report the primary MAAE result or any analyses. Without those results, readers cannot estimate the frequency or precision of the primary outcome, or assess differences between regimens. The listed zero serious adverse-event counts are useful descriptive information but cannot substitute for the unreported primary endpoint or a comparative analysis.

Statistically, the record demonstrates the distinction between a study’s stated objective and the evidence available to answer it. A dose-selection objective does not itself establish which regimen should be used, and planning illustrations do not replace observed results. Transparent endpoint reporting, clear denominators, defined analysis populations, and uncertainty estimates are necessary for readers to judge how much evidence a small early-phase study contributes.

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 main limitation is the absence of reported results for the primary endpoint. The registry record identifies medically attended adverse events as the primary outcome but does not provide the participant count or an uncertainty estimate. It also reports no posted analyses. As a result, the main safety question cannot be evaluated quantitatively from this record.

The non-randomized, sequential design limits comparisons across cohorts. The record itself cautions that the arms are not a like-for-like control comparison. Dose, route or administration schedule, and follow-up differ across the listed cohorts, so apparent differences in event counts should not be attributed to dose alone. The record does not explain the group labels attached to the safety listings.

The safety listings report 11 at risk for Cohort 2, while the arm description states n = 10. The registry record does not explain this discrepancy. It also does not describe the analysis populations, completeness of follow-up, missing-data handling, or event adjudication. The primary endpoint follow-up windows differ by cohort, which affects the period during which events could be observed.

The study is phase 1b and enrollment is reported as 41. The registry record does not report a sample-size justification for the trial, the statistical plan, interim analyses, or how multiplicity was handled. Immunogenicity results, dose-selection criteria, and a reported dose-selection outcome are also absent. These limitations mean the posted information is insufficient to establish comparative safety, immune response, or clinical protection.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: COVID-19 Vaccination Using a 2nd Generation (E1/E2B/E3-Deleted) Adenoviral Platform in Healthy South African Adults — NCT04710303.
• Registry record last updated 2024-11-15; status last verified 2024-04.
• Results first posted 2024-11-15.
• 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

NCT04710303 is a completed phase 1b, open-label, non-randomized, sequential study sponsored by ImmunityBio, Inc. The registry record reports enrollment of 41 healthy South African adults and evaluates hAd5-S-Fusion+N-ETSD. The study began on 2021-03-02 and reached primary completion on 2022-08-02.

The primary endpoint was the number of participants with medically attended adverse events from the first dose through 1 week after final administration. The registry record does not report the primary endpoint result or any statistical analyses. Its safety listings show zero participants with serious adverse events in each listed group, with other affected-participant counts also recorded. These data are descriptive and do not provide a randomized comparison between regimens.

The record does not report analysis populations, missing-data methods, a statistical plan, or immunogenicity results. The study’s dose-selection objective and the criteria or outcome of that selection are not reported in the registry record.