Safety and Immunogenicity Study of Self-Amplifying RNA Pandemic Influenza Vaccine in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Immunogenicity Study of Self-Amplifying RNA Pandemic Influenza Vaccine in Adults (NCT06602531), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Solicited Adverse Events (AEs) Within 7 Days After Each Vaccination.

2. Clinical Question

The study also set out to describe immune responses using hemagglutination inhibition (HAI) and neuraminidase enzyme-linked lectin (ELLA) antibody measures. Those measures were intended to inform dose and schedule selection for further development, alongside safety and reactogenicity. The registry lists antibody outcomes, but their results are not reported in the registry record.

This is a dose- and schedule-finding question rather than a single comparison of one vaccine regimen with one control. The study includes young and older adults and multiple ARCT-2304 regimens, so the relevant interpretation depends on the particular cohort, dose, schedule, and outcome. The registry record does not report a single primary comparison or a prespecified decision rule for choosing a dose or schedule.

3. Trial Design

The registry describes NCT06602531 as a randomized, parallel-design study with quadruple masking and Phase 1 and Phase 2 labels. Its official title describes it as a first-in-human, observer-blind, controlled, dose-level and schedule-finding study. Enrollment is listed as 212, and the status is completed. The recorded study start is 2024-12-10 and primary completion is 2025-06-13.

The trial evaluates ARCT-2304 in young-adult and older-adult groups. The arm descriptions include low-, mid-, and high-dose ARCT-2304 regimens under Schedule 1 and Schedule 2, alongside control regimens. Participants assigned to ARCT-2304 are described as receiving a two-dose regimen. Control participants are described as receiving a licensed influenza control vaccine for the first dose and placebo for the second. The control vaccine is age-specific in the arm descriptions.

The adverse-event listings identify cohorts by dose and by D1,29 or D1,57 schedule labels. The registry record does not explain the allocation procedure, the masking roles, or how enrollment was distributed among arms. The arm descriptions specify intramuscular administration in the deltoid muscle. Participants were asked to complete daily diaries for 7 days after each vaccination and provide blood samples at clinic visits; the summary also describes planned telephone contacts and possible unscheduled clinic visits.

The registry lists safety and reactogenicity as key objectives, with antibody responses measured by HAI and ELLA among the immune-response objectives. The study summary describes comparison with licensed influenza vaccines to help select a dose and schedule for further development. A detailed protocol, statistical analysis plan, or account of how the dose-selection decision was to be made is 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.

Only the first 6 of 8 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: SAF included all participants who received at least one dose of trial vaccine and had any evaluable post-vaccination reactogenicity and/or safety data.

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: Safety analysis set (SAF) included all participants who received at least one dose of trial vaccine and had any evaluable post-vaccination reactogenicity and/or safety data.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Solicited Adverse Events (AEs) Within 7 Days After Each Vaccination, measured over 7 days post each dose.

The primary endpoint is the number of participants with solicited adverse events within 7 days after each vaccination. It covers local events— injection site pain, erythema, and swelling—and systemic events, including fatigue, headache, myalgia, arthralgia, dizziness, nausea, chills, and fever. The fever threshold is listed as ≥100.4 °Fahrenheit /≥38.0 °Celsius. The registry describes the timeframe as 7 days post each dose.

A participant count is a direct way to describe how many people experienced the specified events in the defined observation period. Solicited events are collected through active questioning or diary recording, which differs from relying only on spontaneously reported events. In general, this kind of endpoint can describe short-term reactogenicity across dose and schedule groups; it does not by itself characterize every possible safety outcome or establish that a vaccine caused an event.

The registry defines the safety population for this endpoint as participants who received at least one dose of trial vaccine and had evaluable post-vaccination reactogenicity and/or safety data. However, the primary solicited-event results are not reported in the registry record. The posted adverse-event figures include serious and other adverse-event counts, but they do not provide the endpoint’s solicited local and systemic event results by type and post-vaccination period.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is a count of participants with solicited adverse events, rather than a continuous measurement such as an antibody concentration. Each listed event is a symptom or finding that the study specifically monitored during the post-vaccination period. In general, a participant count can be summarized by group, but interpretation depends on the endpoint definition, observation window, and number of participants with evaluable data. Here, the registry defines a safety population but does not report the solicited-event results needed to interpret the primary endpoint.

What does randomization contribute?

In general, random assignment is intended to make groups comparable with respect to factors that could affect outcomes, on average. It can support a fair comparison when allocation is implemented as planned and outcome collection and analysis are appropriate. The registry identifies the study as randomized but does not report the randomization method, allocation concealment procedures, or whether any departures from assignment occurred. These details are not reported in the registry record.

How should masking be understood?

The registry labels masking as quadruple and the study title describes an observer-blind design. Masking can reduce the possibility that expectations influence participant reports, clinical assessments, or other study decisions. The record does not specify which roles were masked or how masking was maintained, so the exact protections in operation cannot be assessed from the registry description alone.

Why distinguish solicited from other adverse events?

Solicited events are actively collected from a predefined list over a specified period. This makes the observation window and event definitions central to interpretation. Other adverse events may be reported through a different collection process, while serious adverse events are classified by seriousness rather than simply by whether they were solicited. The registry lists the primary solicited endpoint separately from serious and other adverse events. Those categories should not be substituted for one another: counts in one category do not reveal the unreported results in another.

What do the antibody measures represent?

The registry lists HAI and ELLA measures of antibody response. Geometric mean titer describes a group-level antibody titer using a geometric rather than arithmetic scale. A geometric mean fold rise describes change relative to an earlier measurement on that scale. Seroconversion is a prespecified classification of antibody change, but the registry record does not give its operational definition. HAI titers above or equal to prespecified thresholds are another listed outcome. These are distinct summaries and are not interchangeable. Their results, definitions in detail, and analysis methods are not reported in the registry record.

What can a confidence interval tell a reader?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical method. A narrow interval indicates greater precision than a wide interval, but it does not resolve bias, measurement limitations, or problems with the analysis. The registry record does not report confidence intervals for the primary endpoint or the listed antibody outcomes. Thus, the precision of those outcomes cannot be assessed from the posted results.

What is over-dispersion, and is it relevant?

In general, over-dispersion occurs when observed variation in count data exceeds what a chosen probability model expects. If a model assumes less variability than the data contain, its uncertainty estimates may be too small. Whether an over-dispersion issue arises depends on the data and model. The registry record does not report a model for the primary count outcome or information that would allow over-dispersion to be assessed. No claim about its presence or handling can be made.

The record lists no analysis entries. It does not report a statistical analysis plan, model specifications, covariate adjustments, confidence-interval methods, or treatment of repeated event reporting across vaccination periods. Those details are not reported in the registry record, so it is not possible to establish from this listing how repeated observations or comparisons across the multiple groups were handled.

The record also describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The stated effect to detect is a fraction of the observed effect; for time-to-event tables, the stated quantity is total events, while other tables use participants per arm. These are planning assumptions, not evidence about the trial’s design or achieved power. The registry does not report the numerical illustration values in the registry record for this interpretation, and the illustrations should not be read as observed power.

10. Multiplicity, Missing Data and Analysis Populations

The study covers several dose levels, schedules, age groups, and outcome families. The registry lists 24 outcome measures, including safety outcomes and multiple antibody summaries. When many outcomes or group comparisons are examined, the chance of at least one apparently unusual result can increase. In general, a statistical plan can address this through prespecified primary comparisons, a testing hierarchy, adjustment procedures, or a clear distinction between confirmatory and descriptive analyses.

Such details are not reported in the registry record. It does not state whether the study used a multiplicity adjustment, how comparisons were prioritized, or whether dose and schedule selection followed a formal decision rule. Since the record lists zero analyses and does not provide results for the primary solicited-event endpoint or antibody outcomes, no conclusion about the handling or impact of multiple testing can be drawn.

Missing-data methods are also not reported in the registry record. The primary endpoint population is described as participants who received at least one dose and had evaluable post-vaccination reactogenicity and/or safety data. That definition identifies who is included in the described safety population, but it does not explain how missing diaries, incomplete follow-up, unavailable blood samples, or other missing measurements were handled. The record does not report whether analyses used imputation, complete-case methods, or another approach.

The age-specific control groups, multiple schedules, and repeated post-vaccination windows make the analysis population and denominator especially important. The registry provides group-specific at-risk counts for the adverse-event listings, but does not give denominators for the primary solicited endpoint or antibody analyses. It also does not report whether all randomized participants were included in any analysis set. These omissions limit assessment of missingness, comparability, and the scope of any intended statistical conclusions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cardiac failure acute (3.8%), faecaloma (3.8%), tibia fracture (3.8%), pulmonary embolism (3.8%), diplopia (3.7%).

The serious adverse-event listings give, for each group, the number of participants at risk and the number affected. For the D1,29 cohorts, the reported serious-event counts are 0 of 26 for ARCT-2304 1.5 µg, 0 of 26 for ARCT-2304 5 µg, 0 of 27 for ARCT-2304 12 µg, and 0 of 27 for Control/Placebo. For the D1,57 cohorts, the counts are 1 of 27 for ARCT-2304 1.5µg, 0 of 27 for ARCT-2304 5 µg, 2 of 26 for ARCT-2304 12 µg, and 1 of 26 for Control/Placebo.

These are descriptive counts, not estimates of a causal effect or a comparison adjusted for other factors. The registry also reports zero deaths for each listed group. Seriousness does not establish that an event was caused by study treatment; the adverse-event summary describes events regardless of causality. The registry lists cardiac failure acute, faecaloma, tibia fracture, pulmonary embolism, and diplopia with percentages of 3.8%, 3.8%, 3.8%, 3.8%, and 3.7%, respectively. The denominator and event-count context for these percentages are not reported in the registry record.

These serious-event figures are separate from the solicited local and systemic events that define the primary endpoint. The primary solicited-event counts are not reported in the registry record.

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

The record establishes that the study was a randomized, masked, parallel dose- and schedule-finding trial of ARCT-2304 in adults, with licensed influenza vaccine and placebo control regimens. It also documents group-level numbers at risk and affected for serious and other adverse events. Those data can be read as safety listings for the recorded groups, but they do not provide a full account of short-term solicited reactogenicity.

The primary endpoint asks how many participants experienced specified local or systemic events within 7 days after each vaccination. Because those outcome counts are not reported in the registry record, the primary safety question cannot be answered from the posted results. The record also lists multiple antibody outcomes, but gives no results from which to assess the immune responses or compare dose and schedule groups.

The listed serious adverse events should not be interpreted as proof of causation or as a direct comparison of risks. Counts are descriptive, and a small difference in counts does not by itself establish a meaningful treatment effect. The registry does not report comparative effect estimates, confidence intervals, or a statistical analysis plan for these results.

Likewise, the completed status and recorded enrollment do not indicate whether the study met a prespecified safety or immunogenicity objective. They do not establish whether a particular dose or schedule was selected, or whether the vaccine is effective. A dose-selection rationale and any formal decision criteria are not reported in the registry record. The intended use of the study was to help identify a regimen for further development; the posted information alone cannot demonstrate what conclusion was reached.

In general, statistical interpretation separates the observed data from uncertainty and from causal conclusions. Here, the information supports a description of trial structure and selected adverse-event counts, while key endpoint results and analytical details remain absent. Any broader claim about comparative safety, antibody response, or clinical benefit would go beyond what is reported.

13. Why This Trial Matters Statistically

This trial is statistically informative as a design because it varies dose and schedule while including young-adult and older-adult groups and age-specific controls. Such a structure can help distinguish whether observed patterns vary by regimen or population, provided that group-level outcomes and a suitable analysis are reported. The registry describes that design, but the primary solicited-event results and antibody results are not reported in the registry record.

The endpoint structure also illustrates why outcome definitions matter. A count of participants with actively monitored symptoms after vaccination answers a different question from counts of serious adverse events, broader other adverse events, or antibody measures at Day 240. Treating those outcomes as if they were interchangeable would obscure the distinct time windows and clinical meanings built into the study.

Multiplicity is another central statistical issue for a dose- and schedule-finding study. Several regimens and outcome measures create multiple possible comparisons. A transparent analysis plan would clarify which outcomes and contrasts guide interpretation and whether results are confirmatory or descriptive. That plan and its decision criteria are not reported in the registry record.

Finally, this record shows the difference between a registered study design and a complete results account. Trial status and enrollment are useful context, but they do not replace endpoint estimates, denominators, uncertainty intervals, and analysis descriptions. The available safety counts permit limited descriptive reading; the missing primary and immune-response results prevent a complete statistical evaluation of the stated objectives.

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.

Several trial-specific limitations of interpretation follow from the registry record. The primary solicited-event endpoint is defined, but its group-specific results are not reported. This leaves the main short-term reactogenicity outcome unavailable, despite the study’s stated safety focus. Results for the listed HAI and ELLA antibody outcomes are also not reported, so the immune-response objectives cannot be assessed from the registry listing.

The posted serious and other adverse-event counts are descriptive. The record does not provide comparative estimates, confidence intervals, p-values, or an analysis plan for these outcomes. The serious-event term percentages are listed without the denominator and count context needed to interpret their basis. The record’s group-specific at-risk counts for adverse events do not supply the missing denominators for the primary endpoint or antibody analyses.

The trial contains multiple doses, schedules, age groups, and outcome measures. The registry does not report how the planned comparisons were prioritized, how multiplicity was handled, or what criteria would determine dose or schedule selection. It also does not report missing-data methods, the full set of analysis populations, or detailed model specifications. These gaps limit evaluation of precision, comparability, and the robustness of conclusions.

The registry record does not report the age limits defining young and older adults, the exact masking roles, or the randomization procedure. Nor does it describe a formal sample-size justification or interim analyses. The planning assumptions listed for sample-size illustrations are not a substitute for the trial’s design rationale and are not observed power. These limitations mean the available record supports only a partial description of the study and its posted safety data.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety and Immunogenicity Study of Self-Amplifying RNA Pandemic Influenza Vaccine in Adults — NCT06602531.
• Registry record last updated 2026-09-04; status last verified 2026-08.
• Results first posted 2026-09-04.
• 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

NCT06602531 is listed as a completed randomized, quadruple-masked, parallel study with Phase 1 and Phase 2 labels. It enrolled 212 participants and evaluated ARCT-2304 dose levels and schedules in healthy adults, with licensed influenza vaccine and placebo control regimens. The primary endpoint was the number of participants with solicited adverse events within 7 days after each vaccination.

The registry reports group-level serious and other adverse-event counts, including zero deaths in each listed group. However, it does not report results for the primary solicited-event endpoint or the listed antibody outcomes. Statistical analysis details, multiplicity procedures, missing-data methods, and dose-selection criteria are not reported in the registry record. Consequently, the posted information permits a limited description of trial design and selected safety counts, but not a full comparison of the regimens or an assessment of the stated immune-response objectives.