A Study to Evaluate the Safety, Tolerability, and Immunogenicity of the rSm-p80 + GLA-SE (SchistoShield®) Candidate Vaccine in Healthy Adults in Burkina Faso and Madagascar: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety, Tolerability, and Immunogenicity of the rSm-p80 + GLA-SE (SchistoShield®) Candidate Vaccine in Healthy Adults in Burkina Faso and Madagascar (NCT05762393), a randomized phase 1 study. The primary outcome is Proportion of Participants With of Any Serious Adverse Events (SAEs)/ Adverse Events of Special Interest (AESI) From the Time of the First Study Vaccination Through the Final Study Visit..

2. Clinical Question

3. Trial Design

This is a phase 1b, multicenter, randomized, placebo-controlled, observer-blinded, dose-escalation study of the rSm-p80 + GLA-SE candidate vaccine. The registry identifies the design as sequential and the masking as triple. The study was conducted in healthy adults in Burkina Faso and Madagascar, with planned enrollment of 120 participants and three cohorts of 40. The record lists 60 participants planned in each country.

Each cohort was assigned a different antigen formulation: 10 μg rSm-p80 with 5 μg GLA-SE in Cohort A, 30 μg rSm-p80 with 5 μg GLA-SE in Cohort B, and 100 μg rSm-p80 with 5 μg GLA-SE in Cohort C. The registry describes a 3:1 vaccine-to-placebo randomization ratio within each cohort. Participants were scheduled to receive three intramuscular injections on D0, D28, and D56. The study product and placebo volumes are described as 0.5 mL in the cohort descriptions.

The posted primary outcome results list 30 participants in each dose cohort and 30 in the placebo group. The registry does not report how the posted outcome populations relate to the planned country and cohort recruitment beyond its safety-population definition. It also does not report the identity of each masked party or further operational detail about the sequential dose-escalation process.

The registry lists the study as completed, with a start date of 2023-11-17 and primary completion date of 2025-05-19. Its primary objective is to evaluate safety and tolerability across the three formulations. Secondary objectives include antibody seroconversion and geometric mean titers at post-vaccination time points. The record does not report a formal sample-size justification or a detailed statistical analysis plan.

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 investigational product and is summarized according to the treatment cohort.

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 Proportion of Participants With of Any Serious Adverse Events (SAEs)/ Adverse Events of Special Interest (AESI) From the Time of the First Study Vaccination Through the Final Study Visit., measured over Day 1 through Day 224.

The primary endpoint is the number or proportion of participants with any serious adverse event (SAE) or adverse event of special interest (AESI) from Day 1 through Day 224. An SAE is defined in the registry by consequences such as death, a life-threatening event, inpatient hospitalization or its prolongation, persistent or significant disability, a congenital anomaly, or another important medical event that could jeopardize the participant or require intervention to prevent one of these outcomes. An AESI is an event the sponsor considers relevant to monitoring the investigational vaccine’s safety profile.

This endpoint is used to describe potentially important safety events during the specified observation period. Counting participants with at least one event focuses on whether an individual experienced an event, rather than how many events that person experienced. The registry’s safety population includes participants who received at least one dose of investigational product and summarizes them according to treatment cohort.

The endpoint does not capture every dimension of safety by itself. It combines two categories, SAE and AESI, and the record does not provide a separate primary result for each category. Nor does this outcome measure the frequency or severity of all adverse events; other adverse-event counts are listed separately. The registry record does not report the adjudication process or further detail about how events were classified as AESIs.

7. Results Posted in the Registry

• Cohort A: Low-dose Antigen Group (10 μg rSm-p80 + 5 μg GLA-SE): 3.3% (1/30) versus 0.0% (0/30) on control; risk difference 3.3 percentage points (95% CI -3.1 to 9.8); unadjusted two-proportion z-test p = 0.313.
• Cohort B: Medium-dose Antigen Group (30 μg rSm-p80 + 5 μg GLA-SE): 3.3% (1/30) versus 0.0% (0/30) on control; risk difference 3.3 percentage points (95% CI -3.1 to 9.8); unadjusted two-proportion z-test p = 0.313.
• Cohort C: High-dose Antigen Group (100 μg rSm-p80 + 5 μg GLA-SE): 0.0% (0/30) versus 0.0% (0/30) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

For Sm-p80 IgG Antibodies, Seroconversion Rate at Approximately 24 Weeks After Third Dose of Study Vaccination as Compared to Baseline

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Cohort A: Low-dose Antigen Group (10 μg rSm-p80 + 5 μg GLA-SE): 83.3% (25/30) versus 26.7% (8/30) on control; risk difference 56.7 percentage points (95% CI 36.0 to 77.4), risk ratio 3.12 (1.69–5.78); unadjusted two-proportion z-test p = <0.001.
  • Cohort B: Medium-dose Antigen Group (30 μg rSm-p80 + 5 μg GLA-SE): 83.3% (25/30) versus 26.7% (8/30) on control; risk difference 56.7 percentage points (95% CI 36.0 to 77.4), risk ratio 3.12 (1.69–5.78); unadjusted two-proportion z-test p = <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Cohort A: Low-dose Antigen Group (10 μg rSm-p80 + 5 μg GLA-SE) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Cohort B: Medium-dose Antigen Group (30 μg rSm-p80 + 5 μg GLA-SE) than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering Sm-p80 IgG seroconversion and geometric mean titers, assessed after doses and at follow-up after the third dose. These outcomes address whether antibody responses were observed and how antibody levels were summarized. They complement the safety objective by describing immunogenicity, but they answer a different question from whether participants experienced an SAE or AESI.

The posted numeric secondary results include seroconversion at approximately 24 weeks after the third dose. The reported counts show more participants meeting the seroconversion outcome in the low- and medium-dose cohorts than in placebo. The registry also reports unadjusted comparisons for those two cohorts, with p-values of <0.001. The record does not report a corresponding comparison for the high-dose cohort in the posted analyses. It also does not provide numeric results for the other listed time points or geometric mean titer outcomes in the record.

These findings should be considered exploratory in the context of the full outcome set. Multiple secondary outcomes and time points create multiple opportunities to observe apparently notable differences. If no adjustment or prespecified hierarchy is used, unadjusted p-values do not account for that multiplicity and can overstate the strength of evidence when interpreted as confirmatory results. The registry record does not report a multiplicity procedure, a testing hierarchy, or a detailed plan for interpreting the secondary outcomes.

The antibody pattern does not establish clinical effectiveness. Seroconversion and antibody titers are measures of immune response; the registry does not report a clinical disease outcome or evidence that these antibody measures predict protection. They also do not alter the interpretation of the primary safety outcome. The two domains need to be read separately: the primary result describes rare serious or specially monitored events, while the secondary results describe measured antibody responses.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• For Sm-p80 IgG Antibodies, Seroconversion Rate at Approximately 4 Weeks (28 Days) After Each Dose of Study Vaccination as Compared to Baseline
• For Sm-p80 IgG Antibodies, Seroconversion Rate at Approximately 24 Weeks After Third Dose of Study Vaccination as Compared to Baseline
• Geometric Mean Titers (GMTs) of Serum Sm-p80 IgG Antibodies at Approximately 4 Weeks After Each Dose of Study Vaccination.
• Geometric Mean Titers (GMTs) of Serum Sm-p80 IgG Antibodies at Approximately 24 Weeks After Third Dose of Study Vaccination.

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

A risk difference subtracts the observed proportion with an event in the comparator group from the observed proportion in the vaccine group. A positive estimate means the observed proportion was higher in the vaccine group; a negative estimate would mean it was lower. The measure is expressed on the proportion scale, so it describes an absolute difference rather than a relative change. For the low- and medium-dose comparisons, the posted estimate is 0.033. This is a comparison of observed group proportions, not a count of additional events attributed to treatment.

For the high-dose comparison, neither group had a recorded primary event, so the observed difference is 0.0. A zero observed difference in this situation is not the same as proof of identical underlying risk. When events are absent or very sparse, data provide little information about how often an event might occur in a broader population.

How should the confidence interval be read?

A confidence interval describes uncertainty around an estimate under the assumptions of the method used. It is not a range containing a fixed proportion of individual outcomes, and it does not identify the true value with certainty. For the low- and medium-dose primary comparisons, the interval extends from -0.031 to 0.098. Because it includes zero, the data are compatible with no difference as well as with differences in either direction within the interval. The width also indicates that the estimate is not highly precise.

The registry reports an unadjusted p-value of 0.313 for both comparisons. A p-value summarizes how unusual data at least as inconsistent with a null hypothesis would be under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, nor does it measure the size or importance of an effect. The registry does not report a multiplicity-adjusted test or a detailed account of the test used for these primary comparisons.

Why does the number of events matter?

For a binary outcome, the information in a comparison depends strongly on the number of participants and the frequency of events. Here, the primary outcome occurred in one participant in each of two dose cohorts and in no participants in the other two groups. Sparse events make estimates sensitive to each observed event and generally limit precision. A comparison with no events in either group cannot provide the same evidence about relative risk as a comparison with events in both groups.

General statistical context: when event counts are sparse, standard large-sample approximations may be less reliable, and methods designed for sparse data may be considered. The registry record does not report which inferential method was used, whether any sparse-data correction was applied, or whether the reported confidence intervals and p-values came from the same method.

What does the secondary antibody result measure?

The listed secondary outcomes include Sm-p80 IgG seroconversion and geometric mean titers, at time points after vaccination and after the third dose. Seroconversion is a binary outcome indicating whether a participant met the study’s response criterion relative to baseline; the precise criterion is not reported in the registry record. Geometric mean titers summarize antibody levels on a scale suited to values that are positive and often skewed. These outcomes describe immunogenicity, not clinical protection.

For the posted 24-week seroconversion result, the registry includes group counts and unadjusted comparisons for the low- and medium-dose cohorts against placebo. The unadjusted p-values are <0.001 for these comparisons. The record does not report a corresponding inferential comparison for the high-dose cohort or adjusted analyses. A small p-value for a secondary outcome does not by itself establish that an antibody response translates into a health benefit.

How should planning illustrations be understood?

The sample-size illustrations use the observed effect as a starting point and consider planning for 100% of the observed effect, 75% of the observed effect, and 50% of the observed effect. They list participants per arm for 80% power and participants per arm for 90% power. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation.

These are planning illustrations, not observed power and not the study’s documented design justification. The record does not report that the trial was planned using these calculations. In particular, an effect estimated from a small study can be unstable, and planning for a smaller effect produces different sample-size requirements. The illustrations should therefore not be read as proof that the completed study had a particular probability of detecting a true effect.

11. Confidence Intervals and Precision

The primary comparisons have limited precision because very few participants experienced the endpoint. In the low- and medium-dose cohorts, one participant had the composite outcome in each group, compared with none in placebo. The risk-difference interval for each comparison runs from -0.031 to 0.098. It includes zero, so the observed data do not rule out no difference. It also spans values in both directions, indicating uncertainty about the direction and size of any underlying difference.

The point estimate, 0.033, should not be treated as a stable estimate of a small effect without considering the interval and event count. When outcomes are rare, a change in a single observation can meaningfully affect the estimated proportion. The interval gives a more complete account of uncertainty than the point estimate alone, although it still depends on the statistical method and its assumptions. Those methods are not fully described in the registry record.

For the high-dose cohort and placebo, there were no observed primary events in either group, and the reported estimate and interval are 0.0. This exact-looking interval reflects the posted calculation in the observed data; it should not be interpreted as a precise guarantee that the population risks are identical. The registry record does not report an alternative interval or method for handling the zero-event comparison.

The posted secondary seroconversion comparisons for the low- and medium-dose cohorts have risk-difference intervals from 0.360 to 0.774. These are separate immunogenicity outcomes, not evidence that narrows uncertainty about the primary safety endpoint. The registry’s planning illustrations report participants per arm for specified power levels and fractions of the observed secondary effect. Those are hypothetical design calculations under stated assumptions, not measurements of precision in the completed trial and not observed power.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary measures: seroconversion after vaccination and after follow-up, as well as geometric mean titers at corresponding time points. Testing several outcomes and time points increases the chance of obtaining a nominally small p-value by chance if each is assessed separately. Unadjusted p-values are calculated without accounting for this family of tests. The posted 24-week seroconversion comparisons are explicitly unadjusted, and the registry record does not report a family-wise error procedure, false-discovery approach, testing hierarchy, or other multiplicity control.

The record does not report whether the outcome analyses were prespecified in a statistical analysis plan, whether there were interim analyses, or how protocol deviations and missing observations were handled. It does not report the number of participants missing each assessment, reasons for missingness, imputation methods, or sensitivity analyses. These omissions matter because an analysis based only on participants with available measurements can be affected if missingness is related to treatment, outcome, or participant characteristics.

The primary population is described as the safety population: participants who received at least one dose, summarized according to treatment cohort. The registry does not report additional analysis populations, such as a per-protocol or immunogenicity population, or explain whether participants were analyzed according to randomized assignment for every outcome. The posted group sizes are 30 in each dose cohort and 30 in placebo, but the record does not explain participant flow into each analysis set.

The record also does not report a formal sample-size justification, interim monitoring rules, or the decision criteria used in the dose-escalation design. The planning illustrations use an observed effect and stated assumptions, but they are not documented as the trial’s original design calculations. Consequently, they cannot fill the gaps in the registry’s description of planned statistical methods. Interpretation should remain focused on the results and uncertainty that are actually posted.

13. 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: abortion not otherwise specified (3.3%), febrile pneumopathy (3.3%).

The primary safety outcome combines any SAE or AESI over Day 1 through Day 224. One participant in each of the low- and medium-dose cohorts had this composite outcome; none was reported in the high-dose cohort or placebo. No deaths were reported. The low- and medium-dose risk differences are 0.033, with intervals that include zero, and unadjusted p-values of 0.313. These results do not establish a clear comparative difference, but the small number of events also means that the estimates are imprecise.

The registry separately reports other adverse-event counts: 16 in the low-dose group, 21 in the medium-dose group, 22 in the high-dose group, and 19 in placebo. These are not the same as the primary SAE/AESI outcome. The listed serious-event terms include “Abortion Not Otherwise Specified” and “Febrile Pneumopathy,” each reported as 3.3%. The registry record does not identify their treatment groups in this listing or provide enough information to attribute them to the vaccine. These descriptive figures should be read as event reporting, not as proof of causation or as a complete safety profile beyond the observation period.

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

The results describe what was recorded in this phase 1b study during its stated observation period. For the primary composite safety endpoint, there was one event in each of the low- and medium-dose groups and none in the high-dose or placebo group. The comparative estimates for the first two dose cohorts are uncertain, with confidence intervals that include no difference. The zero-event comparison likewise does not establish identical underlying risks.

The record also contains antibody-response results. The reported 24-week seroconversion outcome is more frequent in the low- and medium-dose groups than in placebo, and the corresponding unadjusted comparisons have p-values of <0.001. These results describe immunogenicity. They do not establish that vaccination prevents schistosomiasis, that the antibody response is clinically protective, or that any dose is preferable.

The trial’s enrollment and event counts are limited for evaluating uncommon serious outcomes. A lack of observed events in a group does not show that the risk is zero. Conversely, an event occurring after vaccination does not by itself show that vaccination caused it. The registry record does not provide the detail needed to determine causality for individual events.

The results should not be generalized beyond the study population and design without further evidence. The participants were healthy adults aged 20 to 59 years in Burkina Faso and Madagascar, and the study evaluated three dose formulations in a controlled research setting. The registry does not report results for other populations, longer-term outcomes beyond the stated observation period, or clinical disease outcomes. The findings are therefore a description of the posted study results, not a treatment recommendation or a conclusion about effectiveness.

15. Why This Trial Matters Statistically

This trial raises several statistical issues common in early studies of vaccines: sparse safety events, multiple dose cohorts, a pooled comparator listing, and immunogenicity outcomes that are not clinical disease outcomes. The primary event count is small, so comparative estimates can move substantially with individual observations. Reporting both the risk difference and its confidence interval helps distinguish the observed estimate from the uncertainty around it.

The design also makes clear why dose-specific interpretation needs care. The registry describes sequential cohorts with distinct antigen amounts, while its posted results compare each cohort with placebo. The safety findings are not a simple ranking of doses: the observed event counts are sparse, and the high-dose group’s zero events do not imply a zero underlying risk. Any apparent differences across cohorts should be interpreted in light of that uncertainty and the trial’s early-phase purpose.

The secondary antibody results illustrate another important distinction. A statistical difference in seroconversion is not equivalent to demonstrated clinical benefit. In addition, unadjusted results across multiple outcomes and time points carry less confirmatory weight when the testing plan and multiplicity control are not reported. The registry’s planning illustrations are useful for considering how assumed effects influence design calculations, but they are not evidence of the study’s achieved power or original sample-size rationale.

For biostatistical interpretation, the record is most informative when its target population, endpoint definition, observed counts, uncertainty, and omissions are considered together. It supports a descriptive reading of safety and antibody outcomes in the enrolled study population. It does not resolve questions about rare risks, longer-term outcomes, or the clinical meaning of antibody responses.

16. 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 outcome is a composite of SAE and AESI, but the registry does not provide separate comparative results for those components. The event count is sparse, limiting the precision of risk comparisons. The zero-event result in the high-dose and placebo groups is especially easy to overread as certainty; it records no observed events in those groups, not proof of no underlying risk.

The registry lists a safety population definition but does not report participant flow, missing observations, analysis populations for immunogenicity, or methods used to handle missing data. It also does not identify the test or interval procedure behind the primary comparisons. The record does not report event adjudication, the allocation of listed serious-event terms to treatment groups, or a detailed assessment of event relatedness.

The dose cohorts are sequential, but the registry does not explain operational decision rules for moving between cohorts or provide interim monitoring details. Although the record gives planned recruitment and cohort allocation, it does not explain participant flow into the posted outcome groups. A formal sample-size justification and full statistical analysis plan are not reported.

Secondary findings are limited by incomplete numeric reporting in the registry record and by the lack of a reported multiplicity strategy. The available seroconversion comparisons are unadjusted, while the record lists other antibody outcomes for which numeric results are not reported in the posted data. Neither antibody response nor the primary safety endpoint provides evidence about clinical prevention of schistosomiasis in this record.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of the rSm-p80 + GLA-SE (SchistoShield®) Candidate Vaccine in Healthy Adults in Burkina Faso and Madagascar — NCT05762393.
• Registry record last updated 2026-04-29; status last verified 2026-04.
• Results first posted 2026-04-29.
• 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.

20. Record Summary

The registry identifies NCT05762393 as a completed phase 1b randomized, placebo-controlled, observer-blinded study of rSm-p80 + GLA-SE in healthy adults in Burkina Faso and Madagascar. Planned enrollment was 120. Participants were assigned to sequential low-, medium-, or high-antigen cohorts or placebo, with a three-dose intramuscular regimen described in the record.

The primary endpoint was the proportion of participants with any SAE or AESI from Day 1 through Day 224. One event was posted in each of the low- and medium-dose cohorts and none in the high-dose or placebo group. The low- and medium-dose risk differences were 0.033, with confidence intervals from -0.031 to 0.098 and unadjusted p-values of 0.313. The registry also lists secondary antibody outcomes, including a 24-week seroconversion result, but does not report numeric results for every listed secondary measure.

The record does not report a full statistical analysis plan, multiplicity adjustment, missing-data methods, or formal sample-size justification. Results are descriptive and should be interpreted with the event counts and uncertainty in view.