A Phase 2 Study to Evaluate the Safety, Tolerability, and Immune Response of AFX3772 Vaccine in Healthy Infants: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Study to Evaluate the Safety, Tolerability, and Immune Response of AFX3772 Vaccine in Healthy Infants (NCT05412030), a randomized phase 2 study. The primary outcome is Number of Participants Reporting Any Solicited Injection Site Adverse Events (AEs) After First Dose.

2. Clinical Question

The study was designed to assess safety, tolerability, and immunogenicity in healthy infants. The clinical question therefore has more than one component: whether solicited local reactions were recorded after vaccination, how safety events were characterized, and how pneumococcal serotype-specific antibody outcomes were measured. The registry lists secondary immunogenicity outcomes as the proportion with serotype-specific IgG concentration at or above 0.35 μg/mL and geometric mean concentration for serotype-specific IgG.

The study included two parts with different comparators, so its overall question is not a single comparison of one AFX3772 regimen against one control. Part 1 was a sequential dose-escalation lead-in, with infants randomized 3:1 in cohorts to increasing AFX3772 doses or PCV13. Part 2 assigned infants to one of two AFX3772 dose levels or PCV20. These distinct comparisons matter when interpreting any arm-level safety or immunogenicity results.

The registry record states that a partial clinical hold was placed on the study on 31 October 2024. Enrollment was paused, no further doses of the investigational vaccine were administered, and already-enrolled participants transitioned to standard-of-care pneumococcal vaccine to complete scheduled visits through post-dose 3 and then complete follow-up. Thus, the registered question should be understood in light of the study's reported interruption and subsequent change in vaccination for enrolled participants.

3. Trial Design

This was a randomized, quadruple-masked, sequential Phase 2 study sponsored by GlaxoSmithKline. The registry lists enrollment of 388 and a completed status. The registered start date was 2022-06-16, and the primary completion date was 2025-09-18. The title and summary describe a multi-dose, dose-finding evaluation of AFX3772 against pneumococcal conjugate vaccines in healthy infants.

The study had two parts. Part 1 served as a dose-escalation lead-in and used sequential cohorts. Infants at each dose level were randomized 3:1 to AFX3772 or PCV13. AFX3772 doses in Part 1 were 1 µg, 2 µg, and 5 µg. Part 2 included AFX3772 2 µg and 5 µg groups and a PCV20 comparator. Across the arm descriptions, the planned vaccinations were at 2, 4, and 6 months of age. Participants who did not receive a planned AFX3772 dose received PCV13 in Part 1 or PCV20 in Part 2, according to the arm description.

The study was placed on partial clinical hold by the U.S. Food and Drug Administration on 31 October 2024. The registry says the hold was not related to safety concerns in participants who had already received study vaccines. Enrollment paused, and no additional doses of investigational pneumococcal vaccine were administered. Participants already enrolled transitioned to standard-of-care pneumococcal vaccine to complete scheduled visits through post-dose 3 and subsequently finished follow-up. This interruption is important context for interpreting exposure and follow-up; arm-specific numbers completing each planned dose are not reported in the registry record.

The registry identifies the study as randomized and quadruple-masked, but does not report the specific randomization sequence, stratification factors, or which parties were masked. It also does not report a detailed statistical analysis plan, a sample-size justification, or whether any interim analyses were planned. These design details cannot be inferred from the phase, allocation label, or sequential model. The registry describes the intended comparisons and schedule, but the reported record does not provide enough detail to reconstruct every operational or statistical feature.

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.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Analysis was performed on the SAF, which included participants who received AFX3772 in Part 1 and Part 2 of the study. Only participants with solicited safety data available for the specified time duration were included in this outcome measure.

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: Analysis was performed on the Safety Analysis Set (SAF) which includes all the participants who were randomized and received at least 1 study vaccination with either AFX3772 or PCV.

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Any Solicited Injection Site Adverse Events (AEs) After First Dose, measured over Day 1 to Day 7 post dose 1.

The primary endpoint is the number of participants reporting any solicited injection-site adverse event after the first dose, assessed from Day 1 to Day 7 post dose 1. The listed local reactions are pain or tenderness, redness or erythema, and swelling or induration. A participant counted as having an event regardless of its intensity grade. The endpoint is a participant count, not a count of every reaction episode.

This kind of endpoint is used to describe short-term local reactogenicity after vaccination. Limiting collection to specified symptoms and a defined period makes the outcome more standardized than an unrestricted report of any symptom at any time. Counting participants with at least one specified event gives a straightforward summary of how many experienced a local reaction during that window. General statistical context: a binary participant-level endpoint distinguishes whether an event occurred from how often it recurred or how severe it was; those are different outcomes and require separate definitions.

The registry describes the primary endpoint population as the safety analysis population, including participants who received AFX3772 in Part 1 and Part 2. Only participants with solicited safety data available for the specified duration were included. That wording is relevant because it makes outcome availability part of the analysis population definition. The registry record identifies the endpoint and its timeframe but does not report its numeric results, arm-specific estimates, confidence intervals, or a statistical comparison. Therefore, the endpoint definition can be interpreted, but its observed frequency and comparative precision cannot be assessed from the reported record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study record identifies a randomized, quadruple-masked, sequential design. Those terms describe broad features, not the full analysis method. Randomization is intended to allocate participants by chance, which can help balance measured and unmeasured characteristics across groups in expectation. Masking can reduce the influence of treatment knowledge on care, reporting, or assessment. The record does not report the randomization sequence, masking procedures, or which people were masked, so the practical safeguards cannot be reconstructed in detail.

What does the primary endpoint count?

The endpoint is a binary participant-level outcome summarized as a count: whether each participant reported at least one of the specified solicited injection-site events during Day 1 to Day 7 post dose 1. The endpoint lists pain or tenderness, redness or erythema, and swelling or induration. “Any” means occurrence regardless of intensity grade. General statistical context: a binary endpoint can be summarized as the number or proportion of participants with an event. A count alone does not convey the rate unless its denominator is also stated, and a proportion does not describe the range of uncertainty unless an interval is reported.

The primary endpoint is not a total symptom count, a measure of severity, or a count of events across every dose. It concerns participants after the first dose during the stated window. The registry’s endpoint population also requires available solicited safety data for the specified duration. Participants without such data are not included in that endpoint analysis according to the definition, although the record does not explain how missing observations were handled beyond this eligibility wording.

Why do the two study parts matter?

Part 1 used sequential cohorts and a 3:1 randomization to increasing AFX3772 doses or PCV13. Part 2 included AFX3772 2 µg and 5 µg groups and a PCV20 comparator. This means there are multiple dose groups and comparator vaccines, rather than one uniform randomized comparison across the whole study. A statistical contrast should identify the part, dose, comparator, endpoint, and analysis population it addresses. The registry record does not report a single primary contrast or a complete set of planned contrasts.

General statistical context: comparisons across multiple groups can raise multiplicity concerns when several hypotheses are tested. Without a stated testing hierarchy or adjustment approach, a reader cannot determine whether reported p-values, if any, would control an overall error rate across comparisons. No such multiplicity procedure is reported in the registry record, and no analyses are listed.

How should uncertainty be evaluated?

General statistical context: an effect estimate describes the size and direction of a contrast, while its confidence interval expresses statistical uncertainty under the chosen model and assumptions. For an event-count endpoint, the analysis might report group-specific proportions and a contrast such as a difference or ratio, but the registry record does not report a chosen contrast, model, or primary-endpoint estimate. No confidence interval or p-value for the primary endpoint is reported. It is therefore not possible to assess the precision of a treatment comparison from the primary outcome information.

The safety listings provide affected-participant counts and denominators for serious and other adverse events. These are descriptive counts. They should not be interpreted as adjusted treatment effects, and a count in one arm cannot be directly treated as evidence of a group difference without a defined comparison and uncertainty assessment. General statistical context: sparse event data can yield imprecise comparisons, and the number of participants as well as the event frequency matters for precision. No inferential safety model is reported in the registry record.

What does the planning information mean?

The stated sample-size assumptions describe planning illustrations based on a fraction of an observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The record says these are not the trial's own design calculations. They are planning illustrations, not observed power, and should not be mistaken for a protocol justification or a guarantee that the study could detect a particular effect. The primary outcome was not reduced to one comparison for the planning calculation because it has several categories or time points. Numerical sample-size planning results and an effect estimate are not reported in the registry record.

General statistical context: power calculations depend on assumptions about the target effect, outcome variability or event frequency, allocation, significance threshold, and analysis. If those assumptions do not match the realized study or the intended contrast, the calculated sample size may not represent the actual inferential performance. A planned sample size is distinct from the number enrolled, and neither establishes the precision of a result without the observed outcome data and analysis.

What can be concluded from the registered methods?

The record supports a description of the randomized, masked, two-part design, the endpoint definition, and the broad planning assumptions. It does not support reconstruction of a complete analysis plan. The statistical model, handling of multiplicity, missing-data methods, interim analyses, and detailed analysis populations are not reported in the registry record. Because there are no listed analyses and no quantitative primary-endpoint results, methodological interpretation must remain descriptive rather than inferential.

10. Multiplicity, Missing Data and Analysis Populations

The study includes multiple AFX3772 dose levels, two study parts with different comparators, a primary safety endpoint, and secondary immunogenicity outcomes. The registry lists the proportion of participants with serotype-specific IgG concentration at or above 0.35 μg/mL and geometric mean concentration for serotype-specific IgG. With several doses, outcomes, and possible contrasts, multiplicity is relevant: repeated testing can increase the chance of obtaining at least one apparently notable result by chance. The record does not report a testing hierarchy, an adjustment procedure, or which comparisons were designated as confirmatory.

The missing-data definition for the primary endpoint states that only participants with solicited safety data available for the specified time duration were included. The record does not report how incomplete or partially observed safety data were otherwise handled, whether missingness was assessed by arm, or whether sensitivity analyses were planned. For the immunogenicity outcomes, missing-data handling is not reported in the registry record.

The primary analysis population is described as the safety analysis population, including participants who received AFX3772 in Part 1 and Part 2, with endpoint data available for the defined period. The registry does not provide a fuller description of analysis populations for each outcome or clarify the corresponding comparator population in that endpoint description. The record also does not report whether analyses followed randomized assignment or actual treatment received for every outcome.

No interim analyses or statistical analysis plan are reported in the registry record. The number of analyses is listed as 0, so there are no posted inferential results on which to assess multiplicity, missing-data sensitivity, or population-specific differences. These omissions limit statistical interpretation; they do not establish that a particular procedure was or was not used outside what the registry reports.

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: bronchiolitis (3.4%), stereotypy (3.4%), respiratory syncytial virus bronchiolitis (3.3%), escherichia urinary tract infection (3.3%), gastroenteritis viral (3.3%).

The adverse-event listing gives, for each arm, the number at risk and the number affected for serious adverse events and other adverse events. For serious adverse events, the listed at-risk and affected counts are 30 and 3 for Part 1 AFX3772 1 µg; 32 and 1 for Part 1 AFX3772 2 µg; 30 and 2 for Part 1 AFX3772 5 µg; 29 and 2 for the Part 1 PCV13 comparator; 83 and 7 for Part 2 AFX3772 2 µg; 86 and 6 for Part 2 AFX3772 5 µg; and 86 and 1 for the Part 2 PCV20 comparator. For other adverse events, the corresponding affected counts are 30, 30, 28, 29, 74, 77, and 78, respectively, with the listed at-risk counts of 30, 32, 30, 29, 83, 86, and 86.

These are descriptive participant counts, not adjusted comparisons. The record also lists one death in Part 2 AFX3772 2 µg and zero deaths in each other listed group. The serious-event terms listed include bronchiolitis and stereotypy at 3.4%, and respiratory syncytial virus bronchiolitis, Escherichia urinary tract infection, viral gastroenteritis, and haematemesis at 3.3% each. The registry record does not report the arm attribution or denominators for those term percentages. Serious-event counts do not equal the primary solicited injection-site endpoint, and no causal interpretation or between-arm statistical test is reported.

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

The registry record supports a clear description of what the study set out to assess: safety, tolerability, and immunogenicity of AFX3772 in healthy infants, across two parts and against PCV13 or PCV20. It also gives the definition and timeframe of the primary solicited injection-site endpoint and lists serious and other adverse-event counts by arm. These details are useful for understanding the study's intended comparisons and the available descriptive safety information.

The record does not report quantitative results for the primary endpoint, nor does it list statistical analyses. There are no reported primary-endpoint estimates, confidence intervals, or p-values with which to evaluate how frequently solicited local events occurred or how precisely groups differed. The adverse-event counts are not a substitute for those missing endpoint results because they concern broader safety categories, not the specified post-first-dose local reactions.

The record also does not establish comparative immunogenicity from the information available in its reported results. The secondary outcomes are named, but quantitative outcome estimates and analyses are not reported. Without those data, no statistical conclusion about the magnitude or precision of antibody differences can be made from the registered information.

General statistical context: absence of a reported analysis is not evidence that the groups were equivalent, and a lack of a reported p-value cannot be read as proof of no difference. Conversely, a descriptive event count alone does not establish that an observed difference between arms is systematic. Estimates, uncertainty intervals, and a prespecified comparison are needed to evaluate such questions. The partial clinical hold and transition to standard-of-care vaccine further mean that intended investigational exposure was interrupted for enrolled participants; detailed arm-specific exposure and follow-up results are not reported in the registry record.

Accordingly, the available record documents the trial's design, interruption, endpoint definition, and selected adverse-event counts. It does not provide enough quantitative outcome or inferential information to determine the size, precision, or statistical significance of the primary or secondary comparisons.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a multi-part, dose-finding design in which the comparator changes between study parts. Part 1 used sequential dose-escalation cohorts and PCV13, whereas Part 2 included two AFX3772 dose levels and PCV20. Because those parts do not share one comparator, interpretation requires attention to which part, dose, and contrast a result concerns. A pooled summary across arms could obscure meaningful differences in design and exposure.

The study also illustrates why a clearly defined endpoint and analysis population matter. The primary outcome specifies particular local reactions, a fixed observation period after the first dose, and inclusion only when solicited safety data were available for that period. Those choices determine what the endpoint means and who contributes data. They also limit its scope: it does not summarize all adverse events, later doses, severity, or duration.

Another statistical issue is the relationship between a registered study plan and the actual exposure received. The partial clinical hold paused enrollment and stopped further investigational vaccine dosing, after which already-enrolled participants transitioned to standard-of-care vaccine for scheduled visits through post-dose 3. In that setting, arm-level participant flow, dose receipt, and outcome availability would be important to assess. Those details are not reported in the registry record.

Finally, the record demonstrates the distinction between descriptive safety counts and inferential evidence. It lists serious and other adverse-event counts, but does not report analyses, estimates of uncertainty, or primary-endpoint results. General statistical context: counts can describe what was recorded, while comparisons require an explicit estimand, a defined analysis, and an assessment of precision. The registry information is therefore useful for understanding study structure and safety reporting, but it does not permit a complete quantitative evaluation of the trial's primary or immunogenicity questions.

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 main limitation for statistical interpretation is that the registry record does not report quantitative results for the primary endpoint, despite defining it in detail. It also lists 0 analyses. Consequently, arm-specific primary outcome frequencies, comparative estimates, uncertainty intervals, and p-values are unavailable. The listed adverse-event counts cannot fill that gap because they refer to serious and other adverse events rather than the narrowly defined solicited injection-site endpoint.

The study's partial clinical hold is an additional interpretive constraint. Enrollment was paused and no further doses of investigational pneumococcal vaccine were administered after the hold. Already-enrolled participants transitioned to standard-of-care vaccine to complete scheduled visits through post-dose 3. The record does not report the number of participants who received each planned dose, the arm-specific timing of transition, or detailed completion and follow-up counts. Those omissions prevent assessment of exposure differences and their relation to safety outcomes.

The primary endpoint population includes participants who received AFX3772 in Part 1 and Part 2 and had solicited safety data available for the specified time. The record does not explain how missing data were handled beyond that inclusion condition, or how comparator participants were incorporated into the primary endpoint analysis. It also does not report analysis populations for the listed secondary outcomes.

The registry does not report a complete statistical analysis plan, the prespecified primary contrast, multiplicity control, interim analysis procedures, or sample-size justification. The stated sample-size assumptions are planning illustrations rather than the trial's own design calculation. Finally, the serious-event term percentages are not accompanied by arm attribution or denominators in the registry record, which limits their interpretation. These limitations concern what can be evaluated from the record; they do not determine what may have been analyzed outside the registry.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 2 Study to Evaluate the Safety, Tolerability, and Immune Response of AFX3772 Vaccine in Healthy Infants — NCT05412030.
• Registry record last updated 2026-10-09; status last verified 2026-09.
• Results first posted 2026-10-09.
• 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

NCT05412030 is a completed randomized, quadruple-masked, sequential Phase 2 study of AFX3772 in healthy infants, sponsored by GlaxoSmithKline. Registered enrollment was 388. Part 1 used sequential dose-escalation cohorts with AFX3772 1 µg, 2 µg, or 5 µg and PCV13; Part 2 included AFX3772 2 µg or 5 µg and PCV20. The planned vaccination schedule was at 2, 4, and 6 months of age.

The primary endpoint was the number of participants with any solicited injection-site adverse event from Day 1 to Day 7 post dose 1. The registry also lists pneumococcal serotype-specific IgG outcomes. A partial clinical hold was placed on 31 October 2024; enrollment paused, no further investigational doses were given, and enrolled participants transitioned to standard-of-care pneumococcal vaccine for scheduled visits through post-dose 3 and follow-up.

The record lists serious and other adverse-event counts by arm, but reports 0 analyses and no quantitative primary-endpoint or immunogenicity results. Statistical analysis details, missing-data methods, multiplicity procedures, and sample-size justification are not reported in the registry record.