Safety and Immunogenicity of a Novel Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity of a Novel Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults (NCT05613205), a randomized phase 1 study. The primary outcome is Number of Participants With Solicited Administration-site Events After the First Vaccination.

2. Clinical Question

This was a safety and immunogenicity study, not a trial whose primary question was whether vaccination prevents typhoid or paratyphoid illness. Its primary endpoint concerns short-term, solicited reactions at the administration site. The registry also lists immune-response outcomes, including antibody concentrations and ratios, and additional safety outcomes. Those outcome titles indicate what was assessed, but the registry record does not report their numerical results.

3. Trial Design

The registry identifies this as a Phase 1, randomized, controlled, observer-blind, single-centre study. Its official title describes quadruple masking and a sequential model. It was conducted in healthy adults 18 to 50 years of age in Europe. The study status is completed; the registry dates are 2022-11-28 for study start and 2023-12-06 for primary completion.

The investigational groups covered two dose levels and two formulations: low dose without alum, low dose with alum, full dose without alum, and full dose with alum. The arm descriptions specify intramuscular vaccination on Day 1 and Day 169. The control group received TYPHIM VI on Day 1 and BOOSTRIX on Day 169. The record labels the investigational steps as Step 1a, Step 1b, and Step 2, but does not describe the rules or decisions governing progression between steps.

Enrollment was 97. The adverse-event summary gives group-specific numbers at risk of 12 for each low-dose group and 24 for each full-dose group and the control group. These are the denominators stated for that safety summary; the record does not explain any differences between these denominators and overall enrollment.

The trial was designed to examine safety, reactogenicity, and immune responses. The registry lists 23 outcome measures, but the number of posted analyses is 0. Therefore, the record supports a description of the planned comparison and of the adverse-event summary counts, but not a quantitative account of the primary endpoint or antibody findings. Details of randomization procedures, allocation concealment, masking roles, and the statistical analysis plan 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: Out of 97 participants enrolled, 1 participant, who underwent post-screening procedures, withdrew from the study before randomisation and did not receive the study intervention. Therefore, 96 participants were randomised in the study.

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 solicited safety set, which included all participants who received at least 1 dose of the study intervention and had solicited safety data during the specified timepoints.

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: The analysis population comprised of exposed set which included all participants who were assigned to study intervention.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Solicited Administration-site Events After the First Vaccination, measured over From Day 1 to Day 7.

The primary endpoint is the number of participants with solicited administration-site events after the first vaccination, assessed from Day 1 to Day 7. The specified events are pain, redness, and swelling. The endpoint is a count of participants, rather than a measure of event severity or duration. The registry describes the primary outcome as a count and defines the analysis population as the solicited safety set: participants who received at least one dose of study intervention and had solicited safety data during the specified timepoints.

Solicited events are events specifically asked about during a defined observation period. In general, this approach can make collection of expected, time-limited reactions more consistent than relying only on spontaneous reports. A participant-level count indicates how many people had an event; it does not, by itself, describe how many separate events each person experienced or how intense an event was. Those details are not reported for this endpoint in the registry record.

The endpoint is relevant to the stated safety and reactogenicity purpose: it records local reactions following vaccination. It is not an endpoint for protection against infection or clinical illness. Although the registry specifies the endpoint, time window, and analysis population, it does not report the number of participants with these events. As a result, no event frequency, comparison between groups, or estimate of precision can be stated from the registry record.

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 who experienced solicited administration-site events during a specified time window. In general, a participant-level count reduces each person's experience to whether the event criterion was met. It does not communicate the number of episodes, the intensity of symptoms, or how long symptoms lasted unless those features are separately defined and reported. The registry names pain, redness, and swelling, but does not report results for this endpoint.

For a binary outcome, each participant is classified according to whether the defined event occurred. A group count can be interpreted only alongside its denominator and the endpoint definition. The registry specifies a solicited safety set consisting of participants who received at least one dose and had solicited safety data at the specified timepoints. The analysis details beyond that definition are not reported in the registry record.

What do randomization and masking contribute?

In general, random assignment is intended to reduce systematic differences between treatment groups at the time of assignment. Its ability to do so in a particular study depends on how the sequence was generated, how assignments were concealed, and whether the planned procedures were followed. The registry labels this study randomized, but the sequence-generation and allocation-concealment procedures are not reported in the registry record.

Masking is intended to limit the influence of knowledge about assigned intervention on aspects such as participant reporting, clinical assessment, or study conduct. The official title describes the study as quadruple-masked, and the trial description calls it observer-blind. The identities of the masked parties and the practical masking procedures are not reported in the registry record. The labels therefore describe the design classification, not evidence that masking was maintained.

What can the safety counts tell readers?

Counts are descriptive: they state how many participants were recorded with an event in each group. A count does not, by itself, quantify uncertainty or establish that groups differ. General statistical comparisons would require a defined contrast, suitable analysis, and enough information to assess precision. The registry record reports no analyses, and it does not give a primary endpoint comparison, confidence interval, or p-value. The serious adverse-event counts can be described as posted, but they cannot be converted into a claim of no risk.

In general, a confidence interval expresses a range of values compatible with the data and an analysis procedure. Its width reflects the precision of the estimate under that procedure. No confidence interval for the primary outcome or the posted safety counts is reported in the registry record, so the precision of a treatment-group contrast cannot be evaluated from the record.

What is over-dispersion, and does it apply?

General explanation: over-dispersion occurs when observed variation in count data is greater than expected under a particular statistical model. It matters when a model assumes a specific amount of variation, because underestimated variability can make uncertainty appear too small. The primary outcome in this study is described as a number of participants with an event, rather than a repeated-event count per participant. The registry does not report a model for this endpoint, so it is not possible to say whether over-dispersion was assessed or relevant to the sponsor's analysis.

What do the planning assumptions mean?

The registry's planning illustration is described as based on the observed effect, not as the trial's own design. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. In general, such an illustration asks what sample size a hypothetical design might require under its assumptions. It is not observed power, does not describe the number actually enrolled in a particular arm, and does not establish that the trial was designed around those assumptions. The registry record does not report the trial's sample-size justification. The primary endpoint results needed to interpret an illustration based on an observed primary effect are also not reported in the registry record.

The record does not report the sponsor's statistical model, handling of repeated measurements, covariate adjustment, hypothesis-testing procedure, or interim analyses. No choice among such procedures should be inferred from the trial's phase, design labels, or outcome titles.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists 23 outcome measures, including safety outcomes and antibody concentration or ratio outcomes, but reports 0 analyses. The statistical plan for handling multiple outcomes or multiple comparisons is not reported in the registry record. In general, when many hypotheses are examined, the chance of at least one apparently notable result can increase if no multiplicity strategy is used. This is a general statistical consideration, not a claim about the analyses performed in this study.

The registry does not describe how missing observations were handled, whether any participants were excluded from specific analyses, or whether sensitivity analyses were planned. It defines the primary endpoint population as the solicited safety set: participants who received at least one dose and had solicited safety data at the specified timepoints. Other analysis populations, including populations for immunogenicity outcomes, are not defined in the available record.

Because endpoint counts, participant flow by outcome, and analysis methods are not reported, readers cannot assess the effect of missing data, compare the populations used across outcomes, or determine how any multiplicity concern was addressed. The listed outcome titles identify areas of assessment but do not substitute for an analysis plan or results.

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 non-serious adverse event terms

The adverse-event summary lists 0 participants with a serious adverse event in each group. The numbers at risk are 12 for the low-dose TYP04A group without alum, 12 for the low-dose TYP03A group with alum, and 24 in each of the full-dose TYP04B group without alum, full-dose TYP03B group with alum, and control group. The summary also lists 0 deaths in every group.

These are observed counts in the registry summary. A count of 0 does not show that the true probability of an event is zero; with a limited number of participants, an event may not be observed even when its underlying probability is not zero. The record does not report uncertainty intervals or a statistical comparison for these figures. It also lists other adverse-event counts of 9, 12, 24, 24, and 24 for the groups in the order. Those counts should be read separately from the serious-event figures and from the primary solicited administration-site endpoint. Detailed event descriptions and a statistical analysis are not reported in the registry record.

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

The registry record supports a limited description of a completed Phase 1 study in healthy adults. It identifies the investigational vaccine formulations, comparator regimen, study design labels, and some adverse-event counts. It does not report the primary endpoint results or numerical immune-response results. Thus, it does not permit a reader to estimate the frequency of solicited administration-site events, quantify differences between arms, or assess the precision of those differences.

The serious adverse-event summary reports 0 affected participants in each group, and 0 deaths in each group. This is a description of the posted counts, not proof that serious events cannot occur or that the groups have identical safety profiles. The summary's other adverse-event counts are also descriptive; without fuller event details and analyses they do not establish a comparative safety result.

The record's stated purpose includes safety and immunogenicity in healthy adults, with two doses administered on Day 1 and Day 169. It does not report evidence about prevention of typhoid or paratyphoid disease. The title and outcome list cannot be used to infer clinical protection, durability of protection, or results in groups not represented by the stated healthy-adult population. No treatment recommendation follows from the registry record alone.

In general, a trial's design describes how evidence was intended to be collected, while results and their uncertainty are needed to interpret what the observations support. Here, key numerical results and the analysis plan are not reported in the registry record. Interpretation should therefore remain confined to the posted design information and descriptive adverse-event figures.

13. Why This Trial Matters Statistically

This study is statistically notable as a first-time-in-human, Phase 1 evaluation of a bivalent conjugate vaccine with two dose levels and formulations with or without alum. Its randomized, controlled design creates a framework for comparing investigational groups with a control regimen, while its sequential labeling indicates that the study was organized into steps. The record does not describe the operational rules for those steps, so their statistical implications cannot be specified.

The trial also illustrates why an endpoint definition and an endpoint result are distinct. The primary endpoint is clearly described as a participant count for solicited local events after the first vaccination, with a defined observation window and named event types. Yet the registry record does not report the counts. Without those results, the endpoint cannot answer a comparative question, regardless of how clearly it was defined.

The reported group sizes in the adverse-event summary also place the zero serious-event counts in context: 12 participants were at risk in each low-dose group and 24 in each full-dose group and the control group. In general, the information carried by an observed count depends on the denominator and on uncertainty, not only on whether the count is zero. No uncertainty estimates or comparative analyses are reported for these figures.

Finally, the registry lists 23 outcome measures but reports 0 analyses. That gap matters for statistical interpretation: outcome titles describe what was assessed, but they do not reveal estimates, uncertainty, missing-data handling, multiplicity procedures, or the sponsor's conclusions. The record is therefore useful for understanding the study's stated design and selected descriptive safety counts, while leaving the principal statistical findings unavailable.

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 most important limitation for interpreting this trial from the registry record is that the primary endpoint is defined but its results are not reported. No primary counts, group contrasts, confidence intervals, or p-values are available. The registry also lists 23 outcome measures and 0 analyses, and it does not report numerical results for the listed antibody outcomes.

The adverse-event summary gives group-level counts, but does not include uncertainty estimates or statistical comparisons. For the other adverse-event counts, event-level descriptions, severity, timing, and relationship to the primary solicited endpoint are not reported in the registry record. The number of participants at risk is stated for the safety summary, but participant flow and outcome-specific denominators are not described in further detail.

Several design and analysis details that could affect interpretation are not reported in the registry record: random sequence generation, allocation concealment, identities of the masked parties, the rules for progression through the sequential steps, the statistical analysis plan, missing-data methods, and multiplicity handling. The record also does not report the trial's sample-size justification or interim analyses.

The stated population is healthy adults 18 to 50 years of age in Europe. The registry record therefore does not establish how findings would apply to other populations. Because the primary results and immune-response estimates are absent, these limitations are not matters that can be resolved by interpreting the study's design labels or adverse-event counts alone.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity of a Novel Conjugate Vaccine Against Salmonella Typhi and Salmonella Paratyphi A in Healthy Adults — NCT05613205.
• Registry record last updated 2025-01-24; status last verified 2024-12.
• Results first posted 2025-01-24.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT05613205 is a completed Phase 1, randomized, controlled, quadruple-masked, sequential, single-centre study sponsored by GlaxoSmithKline. It enrolled 97 healthy adults 18 to 50 years of age in Europe. The study evaluated low- and full-dose investigational conjugate vaccines against Salmonella Typhi and Salmonella Paratyphi A, with or without alum, against a control regimen of TYPHIM VI and BOOSTRIX. Vaccine arms received two doses on Day 1 and Day 169.

The primary endpoint was the number of participants with solicited administration-site events from Day 1 to Day 7 after the first vaccination. The record lists 23 outcome measures and 0 analyses, and does not report primary endpoint or immune-response results. The adverse-event summary lists 0 serious adverse events and 0 deaths in each group, alongside group-specific counts for other adverse events. Statistical analysis details, including the plan for missing data and multiple outcomes, are not reported in the registry record.