A Study on the Safety and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against Shigellosis in Adults, Children, and Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study on the Safety and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against Shigellosis in Adults, Children, and Infants (NCT05073003), a randomized phase 1, phase 2 study. The primary outcome is Stage 2: Geometric Mean Concentrations (GMCs) of Anti-serotype Specific Shigella Lipopolysaccharide (LPS)/O-Antigen (OAg) Serum Immunoglobulin G (IgG) in Participants 9 Months of Age in Africa.

2. Clinical Question

The study asked whether the altSonflex1-2-3 candidate vaccine could be evaluated for safety and immune responses across age groups, and which dose merited further development in infants 9 months of age in Africa. The registry describes a first-in-human study that began with adults in Europe, then proceeded through adults and children in Africa to infants in Africa.

Its primary endpoint was the geometric mean concentration (GMC) of serum immunoglobulin G (IgG) against Shigella lipopolysaccharide/O-antigen (LPS/OAg) in infants 9 months of age in Africa. The measurement was taken at Day 281, 28 days after the third study intervention, and was expressed in ELISA units per milliliter. The endpoint was intended to inform selection of a preferred dose for infant vaccine development. The planned statistical comparisons were medium versus low dose in pooled infant groups, and high versus low dose in the dose-finding cohort. Control groups were not analyzed for this endpoint.

This is an immunogenicity question, not a direct test of whether vaccination prevents shigellosis. The primary outcome concerns antibody concentrations, while the registry also lists safety outcomes and secondary immune-response outcomes in adults and children. The registry entries do not include the numerical GMC estimates or confidence intervals, so the size and precision of the reported immune responses are not reported in the registry record.

3. Trial Design

This was a randomized, controlled, sequential Phase I/II study with quadruple masking, described in the official title as observer-blind. It was conducted in multiple countries and used staged age de-escalation. Stage 1 evaluated the high dose and placebo in adults 18 to 50 years of age in Europe. Stage 2 enrolled adults 18 to 50 years of age, children 24 to 59 months of age, and infants 9 months of age in Africa. The registry reports enrollment of 551 and a completed study.

The vaccine was studied at low, medium, and high antigen amounts. In the adult groups, the high dose contained 15 µg of OAg for each of the four Shigella serotypes. For children, the medium dose contained 7.5 µg and the high dose 15 µg of each serotype. In infant groups, low, medium, and high doses were evaluated; the stated amounts for the infant safety cohorts were 3.75 µg, 7.5 µg, and 15 µg of each serotype, respectively. The registry describes two infant cohorts: a safety cohort and a dose-finding cohort. The infant vaccination schedule included three interventions on Day 1, Day 85, and Day 253.

Comparators varied by age group and stage. The registry lists Menveo, Boostrix, Typhim-Vi, Infanrix Hexa, MR-Vac, and placebo among the interventions. Stage 1 placebo recipients were pooled across the two schedules as prespecified in the Statistical Analysis Plan. In the infant dose-finding cohort, MR-Vac was co-administered on Day 1 and Day 253; the safety-cohort schedule differed. Allocation ratios and the detailed randomization procedure 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.

Before assignment: As pre-specified in the Statistical Analysis Plan (SAP), the participants that received placebo in Stage 1 were pooled for all analyses (demography, immunogenicity and safety).

Only the first 6 of 16 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The analysis was performed on the PPS for Stage 2 Infants which included all eligible participants who received all doses as per protocol,had immunogenicity results post-dose,complied with dosing/blood draw intervals,without intercurrent conditions that may interfere with immunogenicity \& without prohibited concomitant medication/vaccination.The PPS for immunogenicity was defined by time point.

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.

Only the first 6 of 17 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Stage 2: Geometric Mean Concentrations (GMCs) of Anti-serotype Specific Shigella Lipopolysaccharide (LPS)/O-Antigen (OAg) Serum Immunoglobulin G (IgG) in Participants 9 Months of Age in Africa, measured over At Day 281 (28 days after the third study intervention).

The primary endpoint was the GMC of serum IgG against Shigella LPS/OAg in infants 9 months of age in Africa, measured at Day 281, 28 days after the third study intervention. ELISA produced concentrations in EU/mL. Four serotypes were tested, but the registry says the planned statistical analysis was performed only for S. sonnei. The planned comparisons were pooled infant medium-dose groups versus low dose, and dose-finding-cohort high dose versus low dose. Control groups were not included in these endpoint comparisons.

General statistical context: antibody concentrations are often summarized with a geometric mean because measurements may be right-skewed, with some values much higher than others. The geometric mean is based on averaging on a logarithmic scale and transforming back to the original scale; it describes a typical concentration while respecting the multiplicative structure of such measurements. It is not the same as an arithmetic average.

The registry specifies a 95% confidence interval (CI) as the measure of dispersion. In general, a CI communicates the uncertainty around an estimated group GMC: narrower intervals indicate greater precision, while wider intervals indicate less precision. A CI is not a range containing every participant’s result, and it does not by itself establish clinical protection. The actual estimates and intervals are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a randomized, controlled trial with quadruple masking and a sequential model. Random allocation is intended, in general, to make treatment groups comparable at the point of assignment by distributing measured and unmeasured characteristics without a systematic allocation rule. Masking can reduce the influence of expectations on participant experience, clinical assessment, and outcome handling. The record does not describe the exact randomization method, allocation ratio, or which roles were masked, so those details are not reported in the registry record.

The sequential design is reflected in the progression from adults in Europe to age groups in Africa. In general, staged enrollment can allow information from an earlier group to inform progression to later groups. The specific progression criteria, review procedures, and decision rules are not reported in the registry record, so no particular safety gate or interim analysis should be inferred.

The primary measure is a geometric mean concentration. In general, a geometric mean summarizes positive, often skewed measurements by taking logarithms, averaging those transformed values, and converting the average back to the original scale. Its interpretation differs from an arithmetic mean: it is suited to multiplicative variation and is less dominated by unusually high values. The primary outcome uses ELISA units per milliliter and specifies a 95% CI. The precise method used to calculate the interval is not reported in the registry record.

The registry identifies a Per Protocol Set for the Stage 2 infant analysis. It describes eligible participants who received all doses as specified, had post-dose immunogenicity results, met dosing and blood-draw timing requirements, and had no intercurrent conditions that could interfere with immunogenicity. General context: a per-protocol analysis focuses on participants who meet prespecified requirements for receiving treatment and having measurements. It can be useful for estimating immune response under adherence to the study procedures, but its results may not represent everyone randomized if exclusions are related to participant characteristics or outcomes. The complete eligibility and exclusion rules are not reported in the registry record.

The stated endpoint analysis uses comparisons of GMCs: pooled medium-dose versus low-dose infant groups, and high-dose versus low-dose groups in the dose-finding cohort. The registry explains that infant safety and dose-finding cohorts were pooled for the medium-versus-low analysis because the dose-finding PPS had fewer than the protocol-defined 72 participants per group needed to ensure power. This pooling is an analysis decision described in the record. The criteria for pooling beyond that explanation, and the method for estimating the comparison and its CI, are not reported in the registry record.

General context: a confidence interval expresses uncertainty in an estimate under the assumptions of the analysis. For a group comparison, an interval around a contrast can help show whether the data are compatible with a range of effects. The registry’s primary endpoint description specifies 95% CIs for GMCs but does not state whether the reported intervals are for each group, a contrast, or both. No numerical estimates or intervals appear in the registry record in the registry record, so there is no basis to characterize their width or direction.

The endpoint description says four serotypes were tested, while the statistical analysis was performed only for S. sonnei. This is narrower than testing each serotype as a primary inferential comparison. The record states that control groups were not analyzed for the primary endpoint because the aim was to identify a preferred dose. It does not report adjustment for multiple comparisons, a hierarchy of hypotheses, or how secondary endpoint multiplicity was handled.

The registry includes a sample-size planning illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that a study had a particular probability of detecting an effect. The trial’s own design justification, planned power calculation, and underlying assumptions are not reported in the registry record. The stated protocol minimum for the infant PPS is an analysis-population condition, not a result showing that the planned analysis attained its intended precision.

General context: over-dispersion occurs when outcome variability exceeds what a simple statistical model assumes. It can make standard errors too small if ignored, leading to overly narrow intervals or misleading tests. The primary endpoint is a continuous antibody concentration, and the registry does not report an over-dispersion model or a particular distributional assumption. It would therefore be inappropriate to assume that such a model was used.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint concerns four tested serotypes, but the registry says the statistical analysis was performed only for S. sonnei. It describes two planned dose comparisons: pooled medium versus low dose and dose-finding high versus low dose. Control groups were excluded from these primary endpoint analyses because the stated objective was dose selection. This focus limits the number of stated primary comparisons, but it does not establish how the study handled the broader set of outcomes.

The registry lists 57 outcome measures, including immune-response outcomes in adults, children, and infants, and antibody threshold outcomes in some groups. The multiplicity strategy across these outcomes is not reported in the registry record. In particular, adjustment methods, hypothesis hierarchies, and rules distinguishing confirmatory from exploratory analyses are not reported. Without that information, the chance of at least one apparently unusual result across many analyses cannot be evaluated from the record.

Missing-data handling is also not reported in the registry record. The primary analysis population requires post-dose immunogenicity results and adherence to specified timing and dosing conditions, but the record does not explain how missing measurements were handled, whether any values were imputed, or how missingness affected inclusion in each comparison. The complete PPS criteria are not reported in the registry record.

General statistical context: restricting an analysis to participants with complete, protocol-compliant measurements can improve consistency of measurement, but it can also change the population represented by the estimate. The direction of any resulting bias depends on why data are missing or participants are excluded; it cannot be determined from the analysis-population definition alone. No missing-data sensitivity analysis is described in the registry record.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (3.3%), faecaloma (2.9%), gastroenteritis (1.2%), epilepsy (1.2%), infantile spasms (1.2%).

The registry’s safety listing reports serious adverse events and other adverse events separately for each study group. The first count in each category is the number at risk; the second is the number affected. For example, in Stage 1 adults, the high-dose group scheduled for Day 1 and Day 85 had 34 at risk for serious events and 0 affected, while the high-dose group scheduled for Day 1 and Day 169 had 34 at risk and 1 affected. The Stage 1 placebo group had 34 at risk and 0 affected by serious events.

Among the infant dose-finding groups, the low-dose group had 82 at risk and 2 affected by serious events; the medium-dose group had 81 at risk and 1 affected; the high-dose group had 83 at risk and 4 affected; and the control group had 82 at risk and 1 affected. One death is listed in the medium-dose infant dose-finding group; deaths are listed as 0 in the other groups.

These are descriptive counts, not estimates of treatment causation. The registry does not provide event-level attribution or a statistical comparison in the registry record presented. Counts should be interpreted within each group’s stage, age, and cohort rather than combined across the study. The most frequently listed serious-event terms and their percentages are Pneumonia, 3.3%; Faecaloma, 2.9%; Gastroenteritis, 1.2%; Epilepsy, 1.2%; Infantile spasms, 1.2%; and Stomatitis, 1.2%. The basis for these percentages is not described in the registry record.

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

The trial’s primary endpoint is an immunogenicity measure: serum IgG concentrations against Shigella LPS/OAg in infants 9 months of age in Africa at Day 281. It is designed to inform dose selection, and the registry states that the primary analysis compares selected vaccine doses rather than vaccine with control. Such an endpoint can characterize measured antibody responses, but it is not a clinical disease outcome.

For that reason, a higher GMC, if reported, would indicate a higher average antibody concentration in the analyzed group, not direct proof of protection from shigellosis. The record does not provide a protective threshold for the primary outcome, nor does it report a relationship between the measured concentrations and clinical disease. The secondary outcomes include antibody levels in other age groups and a threshold measure for some groups, but the registry entries do not include their numerical results.

The study’s staged structure and infant dose-finding cohorts address safety and immune response during development of the candidate vaccine. They do not make all age groups directly comparable: population, region, dose, schedule, cohort, and comparator differ across stages. The infant primary analysis also pools safety and dose-finding cohorts for one comparison and uses the dose-finding cohort for another. Conclusions should therefore remain tied to the specific comparison and analysis population described.

Neither the completed status nor the adverse-event counts establish an overall benefit-harm balance. Serious-event counts are descriptive and do not identify causation. Numerical primary GMCs, confidence intervals, and comparative test results are not reported in the registry record, so the direction, size, and precision of the immune-response comparisons cannot be assessed from these registry entries. The study can be described by its design and intended statistical question, but no dose-ranking conclusion can be supported from the registry entries alone.

13. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early vaccine development: evidence is gathered across age groups and settings while dose selection remains an important objective. A sequential age-de-escalation design moves from adults in Europe to adults, children, and infants in Africa. Each stage answers questions in a different population, so interpretation requires attention to who was enrolled, which dose was used, and how the analysis population was defined.

The infant primary endpoint also shows why analysis populations and pooling decisions matter. The record says the dose-finding PPS had fewer than the protocol-defined 72 participants per group and that safety and dose-finding cohorts were pooled for the medium-versus-low analysis. This decision changes which participants contribute to that comparison and should be considered alongside the separate high-versus-low dose-finding comparison.

Another statistical issue is the distinction between an immune marker and a clinical outcome. GMCs provide a quantitative summary of antibody response, but a concentration is not itself a count of infections or proof of protection. The registry’s decision to analyze only S. sonnei for the primary endpoint, despite testing four serotypes, also makes the scope of inference important to state clearly.

Finally, registry completeness affects what can be concluded. The study is marked completed and includes safety counts, but the primary numerical estimates and uncertainty intervals are not reported in the registry record details. A transparent interpretation must separate the stated design and planned analysis from the missing numerical results, rather than infer a dose preference from study structure or safety counts.

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 primary outcome description contains no numerical GMC estimates, confidence intervals, or comparative test results in the registry record. This prevents assessment of the size, direction, and precision of the primary dose comparisons. Although the outcome description states that four serotypes were tested, it says the planned statistical analysis was limited to S. sonnei. The primary endpoint details therefore do not support conclusions about comparative responses to the other serotypes.

The analysis population was the infant PPS, not all randomized participants. The registry gives some eligibility features but does not report the complete PPS definition or the number contributing to each primary comparison. It also does not describe missing-data procedures or sensitivity analyses. These omissions limit assessment of selection into the analyzed population and the robustness of the results.

The safety and dose-finding cohorts were pooled for the medium-versus-low comparison because the dose-finding PPS had fewer than the protocol-defined 72 participants per group. The record does not give further detail on how the pooling affected comparability or precision. Control groups were not analyzed for the primary endpoint, so the primary dose comparisons do not provide a vaccine-versus-control estimate.

The record does not report the detailed statistical plan, multiplicity adjustments, interim-analysis procedures, or the method used to calculate confidence intervals. The registry’s sample-size illustration is based on the observed effect and stated assumptions, rather than being the trial’s own design justification. Finally, adverse-event counts are descriptive; event attribution and comparative safety analyses are not included in the registry record in the registry record. These limitations constrain interpretation without establishing that any particular result is biased.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study on the Safety and Immune Responses to the GVGH altSonflex1-2-3 Vaccine Against Shigellosis in Adults, Children, and Infants — NCT05073003.
• Registry record last updated 2026-06-22; status last verified 2026-06.
• Results first posted 2026-06-22.
• 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

NCT05073003 is a completed, randomized, controlled, sequential Phase I/II study of the altSonflex1-2-3 candidate vaccine. The registry reports enrollment of 551, quadruple masking, and a staged evaluation beginning with adults in Europe and extending to adults, children, and infants in Africa.

The primary endpoint was infant serum IgG GMC against Shigella LPS/OAg at Day 281, 28 days after the third intervention. The planned comparisons were pooled medium versus low dose and dose-finding high versus low dose; the primary statistical analysis was limited to S. sonnei, and control groups were not analyzed for this endpoint.

Safety counts are listed by group, including one death in the infant dose-finding medium-dose group. Numerical primary GMC results and confidence intervals are not reported in the registry record details, so the dose comparisons cannot be evaluated from the stated information.