Safety, Tolerability, and Immunogenicity Study of Sm-p80 + GLA-SE (SchistoShield(R)) Vaccine in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety, Tolerability, and Immunogenicity Study of Sm-p80 + GLA-SE (SchistoShield(R)) Vaccine in Healthy Adults (NCT05292391), a non-randomized phase 1 study. The primary outcome is Number of Participants Reporting Serious Adverse Events (SAEs) Throughout the Study.

2. Clinical Question

3. Trial Design

This was a Phase 1, open-label, dose-escalation trial of the Sm-p80 + GLA-SE vaccine candidate in healthy adults. It was non-randomized and used a sequential model, with no masking. The registry lists enrollment of 45 participants and five groups, each described as having 9 participants. The study status is completed.

Groups differed by formulation, dose, or timing. Group A received 100 micrograms of Sm-p80 without adjuvant on Days 1, 29, and 57. Group B received 10 micrograms of Sm-p80 plus 5 micrograms of GLA-SE on the same schedule. Groups C and D received 30 micrograms of Sm-p80 plus 5 micrograms of GLA-SE; Group C had its third dose on Day 180, while Group D received it on Day 57. Group E received 100 micrograms of Sm-p80 plus 5 micrograms of GLA-SE on Days 1, 29, and 57. Each injection was described as 0.5 mL and administered intramuscularly.

The stated primary objective was to assess safety and reactogenicity after three doses. Secondary outcomes concerned seroconversion in Sm-p80 IgG antibodies and geometric mean titers at specified times after dosing. The registry lists the start date as 2022-05-23 and primary completion date as 2024-03-19. The planned participant duration is 15 months. Because groups were not randomized and differed in treatment or schedule, contrasts across them are descriptive rather than randomized treatment-effect comparisons. Details of how dose escalation decisions were made are not reported in the registry record.

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: The safety population includes all participants who received at least one dose of the study product and is summarized according to treatment received.

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 Reporting Serious Adverse Events (SAEs) Throughout the Study, measured over Through 12 months after the last study vaccination. For Groups A, B, D, E: Day 1 through Day 422. For Group C: Day 1 through Day 545.

The primary endpoint counts participants reporting serious adverse events throughout the study. A participant is counted as having an event if at least one event meets the study’s seriousness definition; the measure is a participant count, not a count of all event episodes. The registry defines a serious event to include death, a life-threatening event, inpatient hospitalization or prolonged hospitalization, persistent or significant incapacity or substantial disruption of normal life functions, congenital anomaly or birth defect, and certain other medically important events judged to warrant intervention to prevent one of these outcomes.

The endpoint is used in a safety study because serious events can represent important harms requiring clinical attention. Counting affected participants offers a direct summary of how many people experienced an event meeting the definition. It does not convey the full clinical detail of each event, its timing, duration, relatedness to vaccination, or severity beyond the seriousness classification. Those details are not reported in the registry record.

The endpoint timeframe extends through 12 months after the last study vaccination. The listed calendar-day follow-up differs for the delayed-booster group: Groups A, B, D, and E are followed from Day 1 through Day 422, while Group C is followed from Day 1 through Day 545. The primary measure is therefore interpreted in the context of these stated follow-up windows.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary outcome is a count of participants with serious adverse events. This differs from a count of event episodes: if a participant had more than one serious event, a participant-level measure would still count that participant once. The registry describes the safety population as participants who received at least one dose, summarized according to treatment received. The reported group counts use 9 participants at risk in each group.

For this kind of outcome, the observed count is a straightforward description of the participants recorded as having an event. It does not, by itself, estimate how often events would occur in a larger population or under a different follow-up period. General statistical explanation: an estimate is more informative when accompanied by an uncertainty interval, which indicates the range of values compatible with the data under the chosen method. Such intervals for the serious adverse event counts are not reported in the registry record.

How should zero events be understood?

Zero observed events is a valid result, but it is not equivalent to proof of zero risk. When a study includes a limited number of participants, an uncommon event may not occur during the observed follow-up even if it remains possible. General statistical explanation: the information about an event rate depends on both the number of participants observed and the length and completeness of observation. A count without a reported confidence interval leaves the uncertainty unquantified in the registry summary.

The groups have the same reported number at risk, but this does not make them randomized comparison groups. The allocation is non-randomized, and the regimens differ. In addition, Group C had a delayed third dose and a longer listed observation window. These design features matter when interpreting any apparent difference between groups, even if the observed serious-event counts are identical.

Why does the event definition matter?

The primary outcome depends on the registry’s definition of seriousness. It includes specified outcomes such as death, life-threatening events, hospitalization, substantial incapacity, and congenital anomaly or birth defect, as well as other medically important events that may warrant intervention to prevent a serious outcome. The classification therefore relies in part on clinical judgment by the principal investigator or sponsor, as described in the registry definition. A participant’s event can be counted as serious under these criteria even when it does not result in one of the explicitly listed outcomes, if the stated judgment criteria are met.

The endpoint is not a comprehensive description of every reaction after vaccination. Reactogenicity and less serious adverse events are separate safety concerns, and the primary serious-event count does not summarize them. The record lists other adverse events in each group, but event terms and clinical details are not reported in the registry record. The count of participants with other adverse events should not be conflated with the count meeting the serious-event definition.

What can comparisons between groups tell us?

In a randomized trial, random allocation is intended to make groups comparable on average, supporting a causal interpretation of treatment contrasts under the study’s assumptions. Here, the registry identifies allocation as non-randomized. The groups also differ in product composition, dose, or timing. As a result, any observed contrast could reflect those differences or other factors, rather than a single isolated treatment feature. The registry explicitly does not present these arms as a like-for-like control comparison.

General statistical explanation: a statistical test or confidence interval for a treatment contrast cannot remove design limitations such as non-random allocation. No analyses are reported in the registry record, and no p-values or confidence intervals for between-group effects are reported. The posted counts are therefore best read descriptively, within each group and its stated follow-up, rather than as evidence of a comparative treatment effect.

What role do planning calculations play?

Planning calculations based on an observed effect are illustrations of the sample size that might be needed under stated assumptions. They are not a measure of the trial’s observed power, and they do not replace the observed outcomes or uncertainty estimates. General statistical explanation: observed power is not a substitute for reporting effect estimates and their precision. No calculated planning values are reported in the registry record, so no numerical planning conclusion can be drawn from the posted information.

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("Group A: 100 ug Sm-p80 Unadjuvanted", "Group B: 10 ug Sm-p80 + GLA-SE", "Group C: 30 ug Sm-p80 + GLA-SE Delayed Booster", "Group D: 30 ug Sm-p80 + GLA-SE", "Group E: 100 ug Sm-p80 + GLA-SE")
n      <- c(9, 9, 9, 9, 9)
events <- c(0, 0, 0, 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  Group A: 100 ug Sm-p80 Unadjuvanted  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Group B: 10 ug Sm-p80 + GLA-SE  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Group C: 30 ug Sm-p80 + GLA-SE Delayed Booster  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Group D: 30 ug Sm-p80 + GLA-SE  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8
ARM  Group E: 100 ug Sm-p80 + GLA-SE  9  0  0.0  0.0  33.6  -0.0  29.9  0.3  30.8

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary immunogenicity outcomes: seroconversion in Sm-p80 IgG antibodies 28 days after each dose, and geometric mean titers at specified post-dose times. However, the results for these outcomes are not reported in the registry record. The registry lists 8 outcome measures but reports no analyses. The statistical plan for handling multiple outcomes or multiple assessment times is not reported in the registry record.

Multiplicity arises when several outcomes, time points, or group contrasts are examined. General statistical explanation: without an analysis plan that defines the primary comparisons and any adjustment strategy, the chance of finding at least one apparently notable result across many analyses can be difficult to interpret. No multiplicity adjustment, hierarchy of outcomes, or prespecified testing strategy is reported in the registry record. It is therefore not possible to determine how any secondary findings would have been interpreted together, even if results were available.

Handling of missing outcome data, participant withdrawals, and incomplete follow-up is not reported in the registry record. The registry describes the safety population as participants who received at least one dose and says results are summarized according to treatment received. It does not provide participant-level follow-up completeness or explain how missing observations were handled for the primary or secondary outcomes. Those omissions limit assessment of whether the reported at-risk counts reflect complete observation throughout each stated window.

The sample-size justification and any interim analyses are not reported in the registry record. The registry’s listing of a completed study does not itself explain whether enrollment targets, monitoring decisions, or analyses changed during conduct. With no reported analysis methods, precision estimates, or immunogenicity results, interpretation is limited to the descriptive serious adverse event counts and other adverse event counts recorded for the groups.

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 the primary safety outcome, each group has zero participants with a reported serious adverse event among 9 at risk. The registry also lists zero deaths in each group. The follow-up period is stated as through 12 months after the last study vaccination, with Groups A, B, D, and E followed from Day 1 through Day 422 and Group C from Day 1 through Day 545.

These counts mean that no serious adverse event was listed for participants in the reported group denominators during the stated observation windows. They do not establish that serious events are impossible, and they do not quantify uncertainty around the underlying event frequency. No confidence intervals are reported in the registry record.

Other adverse events are listed as affecting 9 of 9 participants at risk in each group. These are reported separately from serious adverse events. The registry does not report the event terms, severity details, or relatedness judgments in the information available for interpretation. Thus, the serious-event counts should not be mistaken for a statement that participants experienced no adverse events of any kind.

Because the study was non-randomized and open-label, these group counts are not a basis for claiming that one regimen had a better or worse safety profile than another. They describe what was recorded in this trial, in groups with different regimens and schedules.

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

The posted results establish a limited descriptive point: the registry lists zero participants with serious adverse events in each of the five groups, with 9 participants at risk in each group. It also lists zero deaths per group. These observations apply to the trial participants and the follow-up windows stated in the registry, not automatically to other populations or longer periods of observation.

The counts do not establish that the vaccine candidate is free of serious risks. A study with 9 participants per group cannot be expected to characterize rare events with precision. General statistical explanation: observing no events in a finite sample leaves uncertainty about the event frequency in a broader population. Because confidence intervals and a detailed safety analysis are not reported, the degree of uncertainty cannot be read directly from the registry record.

Nor do the counts show that one dose, formulation, or schedule is safer than another. Treatment allocation was non-randomized, masking was absent, and the regimens varied. The groups therefore do not constitute a randomized, like-for-like comparison. Equal observed counts do not rule out differences that the study was not able to estimate precisely.

The other-adverse-event counts are separate: 9 of 9 participants at risk are listed in each group. Without event terms or severity descriptions, these counts cannot explain what experiences were captured or how they were judged. They also do not answer the secondary immunogenicity questions. Seroconversion and geometric mean titer results are not reported in the registry record.

Overall, the result is a record of no reported serious adverse events among the listed participants during the stated monitoring periods. It is not a definitive safety conclusion, a comparative treatment-effect estimate, or evidence of an antibody response. Those broader interpretations would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why safety results need to be read together with design and follow-up details. A zero serious-event count is meaningful as an observation, but it does not quantify risk precisely when the group counts are limited. The interpretation depends on the denominator, the time under observation, the event definition, and the completeness of follow-up.

The study also shows how non-randomized dose escalation differs from a randomized comparison. Multiple formulations and schedules are represented, including a delayed third dose in Group C. These groups can describe safety experience under the assigned regimens, but observed differences cannot be cleanly attributed to dose or adjuvant status. The design is suited to studying escalating regimens in an early-phase setting, while limiting causal comparisons across arms.

The distinction between serious and other adverse events is also important. Zero serious events does not mean no adverse events: the registry lists other adverse events for all 9 participants at risk in each group. Without the event terms and descriptions, however, the latter counts cannot be interpreted in clinical detail.

Finally, registry completeness shapes what readers can conclude. The record identifies antibody outcomes but does not report their results, and it does not report analyses, uncertainty intervals, missing-data methods, or a multiplicity approach. Those gaps underscore a statistical principle: a clear outcome definition and a count are useful, but estimates of precision and transparent analysis methods are needed to support broader inferences. The posted safety result is therefore best treated as descriptive evidence from this completed Phase 1 trial.

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.

Several features limit interpretation of the trial-specific results. The study is Phase 1 and includes 45 enrolled participants divided across five groups, each described as having 9 participants. These group sizes provide limited information about uncommon serious adverse events. The record does not report confidence intervals for the event counts, so precision cannot be assessed directly.

Allocation was non-randomized, masking was absent, and the groups received different regimens. This prevents treating the groups as a randomized comparison and complicates attribution of any difference to a single dose or formulation feature. The delayed-booster schedule also has a different stated observation window: Group C is followed through Day 545, while Groups A, B, D, and E are followed through Day 422.

The registry reports other adverse events affecting 9 of 9 participants at risk in each group but does not provide event terms or clinical descriptions in the information available for interpretation. It also does not report participant-level follow-up completeness, withdrawals, or methods for handling missing data. Thus, the extent of complete observation cannot be evaluated from the registry record.

Although antibody seroconversion and geometric mean titers are listed as secondary outcomes, their results are not reported in the registry record. No statistical analyses are reported, and details of multiplicity handling, interim analyses, or sample-size justification are not reported in the registry record. These omissions preclude assessment of the precision of immunogenicity findings or the broader analysis strategy. The available results support descriptive statements about reported safety counts, not broader claims about comparative safety or immune response.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety, Tolerability, and Immunogenicity Study of Sm-p80 + GLA-SE (SchistoShield(R)) Vaccine in Healthy Adults — NCT05292391.
• Registry record last updated 2025-07-14; status last verified 2024-10-30.
• Results first posted 2025-04-11.
• 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

This completed Phase 1 trial evaluated the safety, reactogenicity, and immunogenicity of Sm-p80 with or without GLA-SE in healthy adults between 18 and 55 years of age. It was open-label, non-randomized, and sequential, with 45 participants enrolled across five groups. Regimens varied by dose, adjuvant, or timing of the third intramuscular injection.

The primary outcome counted participants reporting serious adverse events through 12 months after the last study vaccination. The registry lists zero serious adverse events and zero deaths among 9 participants at risk in each group. Other adverse events are listed for 9 of 9 at risk in each group. Antibody outcome results, analyses, and uncertainty estimates are not reported in the registry record.