A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults (NCT05827926), a randomized phase 1, phase 2 study. The primary outcome is Parts 1 and 2: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs).

2. Clinical Question

The trial was designed to evaluate safety, reactogenicity, and immunogenicity, rather than clinical protection against influenza or COVID-19. Part 1 was intended to generate information for selecting an mRNA-1083 composition and dose level for a later Phase 3 trial in adults. Part 2 was intended to add safety and immunogenicity information for other compositions and dose levels in young adults.

The primary endpoint is a participant count for solicited local and systemic reactions recorded in an electronic diary. It covers reactions such as injection-site symptoms, fever, headache, fatigue, muscle or joint pain, nausea or vomiting, and chills. The posted table gives the number of participants with these reactions in each study group. It does not, by itself, indicate how severe an individual reaction was or how long it lasted.

The results therefore address how reaction counts varied across the assigned groups in this study. They do not establish comparative protection against infection, and the immune-response outcomes answer a different question from the short-term solicited-reaction endpoint.

3. Trial Design

This was a randomized, observer-blind, active-control, parallel-group Phase 1/2 study. The registry record lists 1,758 participants enrolled and the study status as completed. ModernaTX, Inc. is listed as the sponsor. The study start date was 2023-04-14, and the primary completion date was 2024-12-03.

The two-part design reflects two related development questions. Part 1 was intended to generate safety, reactogenicity, and immunogenicity data to support selection of an mRNA-1083 composition and dose level for evaluation in a subsequent Phase 3 clinical trial in adults. Part 2 was intended to generate safety and immunogenicity data for additional mRNA-1083 compositions and dose levels in young adults at least 18 years and younger than 50 years.

Across the parts, participants were assigned to multiple vaccine groups. Part 1 included several mRNA-1083 compositions and dose levels, influenza vaccine groups, and COVID-19 vaccine groups. Part 2 included two mRNA-1083 compositions at Dose Levels A through D, investigational influenza vaccine groups at two dose levels, and COVID-19 vaccine groups. The arm descriptions specify a single intramuscular injection on Day 1.

Randomization, observer blinding, and an active-control design are features intended to support a structured comparison of study groups. The registry record does not report the allocation ratio, the detailed randomization procedure, or how the observer-blinding process was implemented. It also does not report whether all arms were enrolled concurrently. Those details matter when considering comparisons that reuse one reference group across multiple cohorts.

The posted primary results include counts from both study parts. The displayed recalculations compare each listed arm with Part 1 Cohort A12, Influenza Vaccine 1. This shared reference is not the same as a separate, necessarily concurrent comparator for every arm. The record does not explain the rationale for using this reference across all displayed comparisons, so interpretation should remain focused on the observed counts and the uncertainty shown for each contrast.

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 37 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The solicited safety set included all randomized participants who receive the study intervention and contribute any solicited AR data. Participants were included in the vaccination group corresponding to what they actually received (as treated).

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 FAS included all randomized participants who received the study intervention. Participants were analyzed according to the group to which they were randomized.

Only the first 6 of 38 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Parts 1 and 2: Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs), measured over Up to 7 days after study injection.

The primary endpoint is the number of participants with solicited local and systemic adverse reactions, measured up to 7 days after study injection. Reactions were recorded by participants using an electronic diary. The specified local reactions were injection-site pain, redness, swelling or hardness, and underarm swelling or tenderness on the same side as the injection. The specified systemic reactions were fever, headache, fatigue, muscle pain, joint pain, nausea or vomiting, and chills.

This endpoint is used to describe short-term reactogenicity: the local and systemic reactions actively sought after vaccination. Counting participants with reactions gives a direct summary of how many people in each group reported at least one of the solicited reactions recorded for the endpoint. It is a different measure from the number of individual symptoms or episodes, and it is not a measure of antibody response or protection against disease.

The safety population for this endpoint included randomized participants who received study intervention and contributed any solicited reaction data. Participants were classified according to the intervention they actually received. This is an as-treated approach for the listed endpoint, rather than an analysis that necessarily retains everyone in the group originally assigned.

The posted result is a count by arm, and the comparison section expresses differences between groups as risk differences. These summaries describe the proportion of participants with reported reactions, but the endpoint does not separate results by each reaction type in the displayed primary table. Severity grades, duration, and the pattern of individual local versus systemic symptoms are not reported there. The endpoint is useful for comparing short-term reported reactions across groups, but it does not summarize every aspect of safety.

7. Results Posted in the Registry

• Part 1 Cohort A13: Influenza Vaccine 2: 67.9% (36/53) versus 59.3% (32/54) on control; risk difference 8.7 percentage points (95% CI -9.5 to 26.8), risk ratio 1.15 (0.86–1.53); unadjusted two-proportion z-test p = 0.352.
• Part 1 Cohort A11: Investigational Influenza Vaccine 2: 68.5% (37/54) versus 59.3% (32/54) on control; risk difference 9.3 percentage points (95% CI -8.8 to 27.3), risk ratio 1.16 (0.87–1.54); unadjusted two-proportion z-test p = 0.317.
• Part 1 Cohort A8: Investigational Influenza Vaccine 1: 84.3% (43/51) versus 59.3% (32/54) on control; risk difference 25.1 percentage points (95% CI 8.6 to 41.5), risk ratio 1.42 (1.11–1.83); unadjusted two-proportion z-test p = 0.005.
• Part 1 Cohort A10: COVID-19 Vaccine 1: 77.8% (42/54) versus 59.3% (32/54) on control; risk difference 18.5 percentage points (95% CI 1.4 to 35.7), risk ratio 1.31 (1.01–1.71); unadjusted two-proportion z-test p = 0.038.

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.

Part 2: SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Part 2: Investigational COVID-19 Vaccine 2: 43.3% (13/30) versus 40.5% (15/37) on control; risk difference 2.8 percentage points (95% CI -21.0 to 26.6), risk ratio 1.07 (0.61–1.88); unadjusted two-proportion z-test p = 0.818.
  • Part 2: mRNA-1083 Composition 1 Dose Level 1: 36.1% (13/36) versus 40.5% (15/37) on control; risk difference -4.4 percentage points (95% CI -26.7 to 17.9), risk ratio 0.89 (0.50–1.60); unadjusted two-proportion z-test p = 0.697.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Part 2: Investigational COVID-19 Vaccine 2 and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Part 2: mRNA-1083 Composition 1 Dose Level 1 and the control. The interval gives the range of effects that remain compatible with the data.

The registry describes a broader secondary program than the one fully displayed in the results excerpt. Listed outcomes include antibody geometric mean titres and fold rises for influenza and SARS-CoV-2, influenza seroconversion, SARS-CoV-2 seroresponse, and SARS-CoV-2 geometric mean concentration. The detailed secondary results are for the Part 2 SARS-CoV-2 seroresponse endpoint measured by PsVNA from Day 1 to Day 181.

Across that displayed endpoint, the estimated seroresponse percentages vary among the vaccine groups, and the reported 95% confidence intervals are broad. The posted unadjusted comparisons with the Part 2 COVID-19 Vaccine 2 reference include intervals that span zero. This pattern indicates uncertainty in the differences in these small groups; it does not establish equivalence between groups. Other listed secondary outcomes are not reported in the registry record with comparable arm-level results in this data extract.

These immune-response results relate to, but do not answer the same question as, the primary safety endpoint. The primary outcome counts solicited reactions during the period up to 7 days after injection. The secondary seroresponse outcome assesses an antibody response through Day 181. Neither can be substituted for the other: a reaction count does not measure antibody response, and an antibody response is not a direct measure of clinical protection against infection.

Secondary outcomes are useful for describing the development profile of different compositions and doses, especially in a study whose stated purpose includes composition and dose selection. They warrant more caution when many outcomes and groups are considered together. The posted comparisons are unadjusted, the registry record does not report a multiplicity procedure, and no reported analyses are listed for the displayed secondary endpoint. Consequently, individual secondary p-values should carry less weight than the overall pattern, the estimates, and their uncertainty. The record does not establish that a particular secondary difference was a prespecified confirmatory finding.

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

• Part 1: GMT of Antibodies for Influenza, as Measured by HAI Assay
• Part 1: GMT of Antibodies for SARS-CoV-2, as Measured by PsVNA
• Part 1: GMFR of Antibodies for Influenza, as Measured by HAI Assay
• Part 1: GMFR of Antibodies for SARS-CoV-2, as Measured by PsVNA
• Part 1: Influenza: Percentage of Participants With Seroconversion, as Measured by HAI Assay
• Part 1: SARS-CoV-2: Percentage of Participants With Seroresponse, as Measured by PsVNA
• Part 2: GMT of Antibodies for Influenza, as Measured by HAI Assay
• Part 2: GM Concentration of Antibodies for SARS-CoV-2, as Measured by PsVNA

9. Statistical Interpretation

10. Statistical Methods Explained

General explanation: A binary endpoint records whether each participant did or did not meet a definition. Here, the posted primary outcome is the count of participants who reported solicited reactions. Dividing a count by the corresponding group size gives a group proportion; the displayed comparison estimates use the difference between two such proportions. The risk difference is expressed on the proportion scale, so a positive estimate means the compared arm had a higher observed proportion than the reference arm. It is not a risk ratio or an odds ratio.

The comparison table also includes intervals and unadjusted p-values. An interval communicates a range of values compatible with the observed data under the calculation used. If it spans zero for a risk difference, the data are compatible with both a higher and a lower underlying proportion in the compared arm. If it does not span zero, that does not prove the difference is clinically important or remove the possibility that the result reflects chance, especially when many arms are being compared.

The displayed primary comparisons are simple unadjusted recalculations from the posted summary counts. They do not account for covariates, stratification, clustering, or adjustment for the number of comparisons. The registry record lists zero reported analyses for this outcome. A detailed sponsor statistical analysis plan or adjusted model for these contrasts is not reported in the registry record. The posted calculations are therefore useful descriptive comparisons, but they should not be mistaken for a prespecified, multiplicity-controlled analysis.

The primary endpoint population is defined by receipt of study intervention and contribution of any solicited reaction data. Classification is based on the intervention actually received. This definition makes the analysis population explicit, but the record does not give details of how missing diary entries were handled or how many participants lacked the relevant data by arm. The group sizes in the results should be read as the denominators shown for the particular result, rather than assumed to include every randomized participant.

General explanation: Randomization can help balance participant characteristics across groups on average, while masking can reduce the influence of expectations on reporting or assessment. The registry record describes the study as randomized and triple-masked, but does not specify the operational details of masking. Solicited symptoms are participant-reported, so diary completion and awareness of group assignment could matter to measurement. The record does not describe procedures for checking diary completeness or validating reported reactions.

The study uses an active-control structure and many intervention arms. The displayed contrasts use the Part 1 Cohort A12 influenza vaccine group as a common reference. This means each risk difference is a comparison with that same group, rather than a direct comparison among all pairs of experimental arms. Differences between two experimental arms cannot be inferred by comparing their separate p-values against the reference. The registry record does not report a model that jointly estimates all arms or a procedure for accounting for the shared control.

For immunogenicity, the posted Part 2 secondary endpoint is the percentage of participants with a SARS-CoV-2 seroresponse, measured by PsVNA from baseline on Day 1 to Day 181. The table presents an estimate and a 95% confidence interval for each listed group. These percentages describe antibody-response criteria, not clinical infection outcomes. The posted secondary comparison calculations are unadjusted and the registry record lists no reported analyses for that endpoint.

The registry lists other secondary outcomes involving geometric mean titres, geometric mean fold rises, geometric mean concentrations, seroconversion, and seroresponse. These measures summarize antibody levels or changes in antibody levels in different ways. A geometric mean is based on a transformed scale and is often used for antibody measurements that vary over a wide range. Fold-rise measures compare post-baseline values with baseline values. The registry record does not report a full statistical analysis plan explaining transformations, missing immune samples, assay handling, or the exact analysis populations for every secondary endpoint.

General explanation: Multiplicity arises when a study makes many statistical comparisons or examines many outcomes. Each unadjusted p-value addresses a single comparison under its calculation assumptions; it does not account for the entire collection of comparisons. Adjustment methods can change the interpretation of evidence across a family of tests, but the registry record does not report such a method. The lack of a reported adjustment does not mean one was or was not used outside the posted record; it means that the registry record does not document it.

The listed primary event counts and secondary antibody results answer distinct questions and have different timeframes. The primary endpoint concerns solicited reactions up to 7 days after injection, while the displayed seroresponse endpoint extends to Day 181. A short-term safety count cannot substitute for an immune-response analysis, and an antibody response cannot establish clinical effectiveness. The study’s stated purpose was to gather early safety and immunogenicity information for composition and dose selection, which is consistent with a development-stage trial containing multiple arms rather than a single confirmatory comparison.

11. Confidence Intervals and Precision

Precision describes how much uncertainty remains around an estimate. The interval accompanying a risk difference gives more information than the point estimate alone: a wide interval indicates that the observed groups do not pin down the underlying difference closely. Several primary contrasts have intervals that extend across zero, so the posted data are compatible with more than one direction of difference. Other intervals lie above zero, but those estimates still have uncertainty and are among many unadjusted comparisons.

Group sizes vary across the arms, and the displayed primary groups are small relative to the overall enrollment of 1,758. Smaller group sizes generally yield less precise estimates for binary outcomes, especially when the event proportion is neither near zero nor near one. This is a general statistical principle; it does not determine the result for any specific contrast. The interval estimates in the table should be used to judge precision for each comparison rather than relying on the point estimate alone.

The Part 2 SARS-CoV-2 seroresponse table explicitly reports 95% confidence intervals. For example, the estimate for Part 2: COVID-19 Vaccine 2 is 40.5 with a 95% confidence interval from 24.8 to 57.9, based on 37 participants in that analysis. Several other intervals are also broad. That spread shows that the secondary estimates are not highly precise in these groups, and overlapping intervals are not by themselves a formal test of differences between arms.

The primary comparison intervals are shown alongside the recalculated risk differences. The confidence level for those comparison intervals is not reported in the registry record, so they are described simply as the reported intervals rather than assigned a confidence level. In general, an interval is not a guarantee that the true value lies inside it; it is a way to express sampling uncertainty under a statistical procedure and its assumptions. Precision should be considered alongside the number of arms, the shared reference group, and the lack of a reported multiplicity adjustment.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size table and curve translate an observed contrast into planning illustrations. Because the endpoint is binary rather than time-to-event, the displayed figures are participants per arm, not total events. The table shows planning for the full observed effect and for smaller fractions of that observed effect. It is not a reconstruction of the study’s original enrollment plan: the trial’s own original design assumptions are not reported in the registry record.

The stated planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is the stated fraction of the observed effect. Under those assumptions, the 80% power column gives the planned number of participants per arm for an 80% chance of detecting that assumed effect if it is present. The 90% power column gives the corresponding number per arm for a 90% chance. These are planning concepts, not guarantees about the results in a future study.

The smaller the effect targeted, the more participants are generally needed to distinguish it from random variation. This pattern is visible in the tables and curve: planning for 75% or 50% of an observed effect usually requires more participants per arm than planning for 100% of that effect. Estimates based on very small observed contrasts can therefore produce very large planning figures. Such figures reflect the selected assumptions and observed contrast; they should not be read as evidence that the original study was designed to detect that exact effect.

These values are not observed power. They are forward-looking illustrations based on a particular effect assumption and calculation method. They do not account for every feature that could affect a real study, such as different allocation, missing outcome data, multiplicity, or a different underlying event rate. Use them to understand how assumptions about effect size and power influence sample-size planning, not as a post hoc score for the trial.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.593; treatment proportion p₁ = 0.679; average p̄ = 0.636.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6805 = 1.3337.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6777 = 0.5704.
4. n = (1.3337 + 0.5704)² / (0.0867)² = 482.9, rounded up to 483 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
p0 <- 0.592592592592593                          # control proportion
p1 <- 0.679245283018868                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(5827926)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 483 (80% power), 646 (90% power)
 75% of observed effect: n per arm = 870 (80% power), 1,164 (90% power)
 50% of observed effect: n per arm = 1,981 (80% power), 2,651 (90% power)
power.prop.test: 482.9 
Simulated power at n = 483 per arm: 0.794 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Multiplicity, Missing Data and Analysis Populations

This study includes many intervention arms, multiple dose levels, two study parts, and several secondary antibody outcomes. Each additional comparison creates another opportunity for a result to appear notable by chance. The displayed p-values are unadjusted, and a multiplicity adjustment is not reported in the registry record. They should therefore be interpreted as individual, exploratory comparisons rather than as confirmatory evidence across the full set of arms and outcomes.

The record lists no reported analyses for the primary or displayed secondary comparisons. The detailed statistical analysis plan, including any prespecified hierarchy of outcomes, family of comparisons, or adjustment method, is not reported in the registry record. Interim analyses and any decision rules for selecting compositions or doses are also not reported in the registry record. The study summary explains that Part 1 was intended to support selection for a later Phase 3 trial, but does not document the statistical selection procedure.

The primary analysis population includes randomized participants who received intervention and contributed any solicited reaction data, classified according to what they actually received. That definition is informative, but it does not fully describe missing-data handling. The registry record does not report the number or pattern of missing diary entries by arm, whether incomplete diaries were imputed, or how participants with partial reaction data were treated beyond the stated eligibility for the safety set.

For secondary immunogenicity outcomes, the displayed analysis denominators differ from the primary safety denominators. The record does not explain all reasons for these differences or give a complete account of missing blood samples, assay results, or analysis-set definitions for each endpoint. The primary completion date and overall enrollment are reported, but they do not resolve these analysis details.

These reporting gaps do not prove that the sponsor did not consider multiplicity or missing data in its internal work. They mean those procedures cannot be assessed from the registry record. As a result, estimates and unadjusted p-values are best treated as descriptive signals that require cautious interpretation, especially where many arms share a common reference group.

15. 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: upper respiratory tract infection (3.0%), renal pseudoaneurysm (2.7%), intestinal obstruction (2.6%), sepsis (2.6%), seizure (2.6%).

The serious adverse event section presents the number of participants at risk and the number affected by serious adverse events, other adverse events, and deaths for each listed group. These are participant counts, separate from the solicited-reaction endpoint. The serious-event counts are small across the individual groups, and the posted table should be read arm by arm rather than as a ranking of vaccine safety.

The registry also lists selected serious-event terms with percentages, including upper respiratory tract infection, renal pseudoaneurysm, intestinal obstruction, sepsis, seizure, and coeliac artery compression syndrome. The record does not provide context for those percentages, such as the specific denominator or how the terms were selected. They should not be interpreted as comparative rates between intervention groups.

No deaths are listed in the group-level serious adverse event data. This is a description of the posted record, not proof that no safety concern occurred or that the groups can be ranked. The study has many arms and relatively small group sizes, so counts alone provide limited precision for uncommon events. The record does not provide a statistical comparison of serious-event rates.

Serious adverse events are distinct from the solicited local and systemic reactions counted during the 7-day primary endpoint period. The two sections have different definitions and should not be combined. The registry record does not provide enough detail in this excerpt to characterize event timing, relatedness assessments, severity distributions, or follow-up beyond the counts shown.

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

The results describe what was recorded in this Phase 1/2 study: counts of participants reporting solicited local or systemic reactions after injection, along with immunogenicity outcomes for some groups. The primary table shows that the observed reaction counts varied across the active-control and investigational arms. The recalculated risk differences and intervals quantify those observed contrasts, but they do not establish why the groups differed or whether a difference would persist in a larger study.

The trial was designed to gather early safety and immunogenicity information and, in Part 1, to support selection of a composition and dose level for further study. That purpose is different from demonstrating clinical effectiveness. The posted antibody-response endpoint is a laboratory measure, and the primary reaction endpoint is a short-term safety measure. Neither directly measures prevention of influenza or SARS-CoV-2 infection.

Interpretation is constrained by the number of arms, the use of a common reference group, relatively small group sizes, and the lack of a reported multiplicity procedure for the displayed comparisons. Intervals for individual estimates show uncertainty, while unadjusted p-values do not account for the full set of tested contrasts. A result that looks different in one arm should therefore be considered in the context of the entire table, the study’s development-stage purpose, and the uncertainty around estimates.

The results also apply to the study populations and timeframes represented in the record. Part 2 involved young adults at least 18 years and younger than 50 years, and the primary solicited-reaction endpoint covered up to 7 days after injection. The registry record does not establish how these results generalize beyond those groups or time periods. This page describes the posted data and their precision; it is not a recommendation about vaccination or treatment.

17. Why This Trial Matters Statistically

Statistically, this study illustrates the challenges of evaluating many vaccine compositions and dose levels in an early development program. A single trial can produce useful descriptive information across safety, reactogenicity, and immunogenicity, while still leaving important questions unresolved. The two-part structure reflects a progression from gathering data to inform composition and dose selection to assessing additional options in a younger adult population.

The parallel-group, randomized design and active controls provide a framework for comparing groups. At the same time, the number of arms creates a need to distinguish exploratory patterns from confirmatory findings. The primary results include one shared reference group and many unadjusted comparisons; the secondary program covers several immune measures. This makes transparent reporting of the analysis plan, multiplicity strategy, and missing-data methods especially important for readers assessing how strongly to interpret individual results.

The page also demonstrates why point estimates should be read alongside intervals. A difference can appear large in a small cohort while still having substantial uncertainty. Conversely, an interval that includes zero does not prove that groups are identical. Planning illustrations add a separate lesson: assumptions about the effect size to detect have a major influence on the required number of participants, and planning calculations based on an observed contrast are not the same as the trial’s original design rationale.

Finally, the primary endpoint and antibody outcomes represent distinct dimensions of a development decision. Short-term solicited reactions describe reactogenicity, while antibody measures describe immune response. Keeping those endpoints separate helps prevent a laboratory response from being mistaken for clinical effectiveness or a reaction count from being treated as a complete account of safety. The record’s stated aims make these distinctions central to reading the results responsibly.

18. 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.

A central limitation is the broad set of arms and comparisons. The primary comparisons use Part 1 Cohort A12, Influenza Vaccine 1, as the shared reference, including for arms in Part 2. The registry record does not establish whether all compared cohorts were concurrent or otherwise directly comparable. A common reference permits a consistent display, but does not remove possible differences between cohorts or study parts.

The group sizes shown in the primary results are modest, and some listed groups include 33 participants. Smaller groups yield less precise estimates, particularly for binary outcomes. The intervals show that several comparisons remain uncertain. The study’s total enrollment of 1,758 should not be mistaken for the size of each arm or the denominator for every endpoint.

The primary endpoint combines solicited local and systemic reactions in a participant count. The posted table does not break the results down by individual symptom, severity, duration, or the number of reactions per participant. Diary contribution is part of the analysis-set definition, but the registry record does not report detailed missing-diary handling or completeness by arm.

The posted recalculations are unadjusted, and a multiplicity method is not reported. The registry record also does not provide a detailed statistical analysis plan, a complete account of interim analyses, or the original sample-size justification. These omissions limit assessment of prespecification and the role of the comparisons in selecting doses or compositions.

For immunogenicity, the displayed Part 2 seroresponse estimates have broad 95% confidence intervals and differing analysis denominators. Other listed secondary outcomes are not reported with full arm-level results. The available antibody-response results cannot establish clinical protection, and the short-term reaction endpoint cannot describe all dimensions of safety. These limitations are specific to the scope and reporting of this record.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of mRNA-based Influenza and SARS-CoV-2 (COVID-19) Multi-component Vaccines in Healthy Adults — NCT05827926.
• Registry record last updated 2025-12-23; status last verified 2025-12.
• Results first posted 2025-12-23.
• 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.

22. Record Summary

This completed randomized, observer-blind, active-control Phase 1/2 study enrolled 1,758 healthy adults and evaluated mRNA-based influenza and SARS-CoV-2 multi-component vaccines. Participants received a single intramuscular injection, with multiple compositions, dose levels, and vaccine groups across Part 1 and Part 2.

The primary endpoint counted participants with solicited local or systemic adverse reactions up to 7 days after injection. Posted arm-level counts vary, and the displayed risk differences are unadjusted recalculations against Part 1 Cohort A12, Influenza Vaccine 1. The study also included antibody-response outcomes; the detailed secondary results concern Part 2 SARS-CoV-2 seroresponse through Day 181.

The record describes a development-stage study intended to inform safety, immunogenicity, and composition or dose selection. Many arms, a shared reference group, uncertain estimates, and unreported analysis details limit confirmatory interpretation. The posted results describe observed outcomes in this trial; they do not demonstrate clinical effectiveness.