A Study of mRNA-1010 Compared With a Licensed Influenza Vaccine in Adults ≥50 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of mRNA-1010 Compared With a Licensed Influenza Vaccine in Adults ≥50 Years of Age (NCT06602024), a randomized phase 3 study. The primary outcome is Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs).

2. Clinical Question

3. Trial Design

This was a randomized, observer-blind, active-controlled, parallel-group Phase 3 study. The registry lists triple masking. Enrollment was 40805, and the study status is completed. The recorded start date is 2024-09-16 and primary completion date is 2025-08-21. The registry describes the study as case-driven.

Participants were assigned to receive a single Day 1 injection of mRNA-1010 or a licensed inactivated seasonal influenza vaccine. The active-comparator arm could receive TIV or QIV, with four product names listed in the record. The registry’s primary solicited safety population includes randomized participants who received a study vaccination and contributed solicited-reaction data; analysis was according to the vaccination actually received. That definition matters because it describes the population used for the posted primary outcome, rather than necessarily every randomized participant.

The study’s stated primary objectives were to evaluate safety and reactogenicity and relative vaccine efficacy against RT-PCR-confirmed protocol-defined ILI caused by any influenza A or B strains. The primary outcome measure posted in the results concerns solicited local and systemic adverse reactions. Secondary outcomes include additional ILI definitions, ILI with antigenic match to vaccine strains, and hemagglutination inhibition (HAI) measures of antibody response.

The registry record does not report the original sample-size justification, detailed allocation procedures, or the study’s full statistical analysis plan. It also does not report how many participants received each specific licensed comparator product. Those details cannot be inferred from the overall trial description or the posted outcome results.

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: A total of 40805 participants were randomized; 20402 participants to the mRNA-1010 group and 20403 participants to the standard dose comparator group. Participants were followed up for up to Day 181 for safety assessment and for up to 7.5 months (up to end of influenza season) for efficacy assessment.

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 received any study vaccination and contributed any solicited AR data. Participants were analyzed according to the study vaccination they actually received.

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: Randomization set included all participants who were randomized, regardless of the participants' treatment status in the study. Participants were analyzed according to the treatment group to which they were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs), measured over Day 1 up to Day 7.

The primary outcome counts participants with solicited local or systemic adverse reactions recorded from Day 1 up to Day 7. Local reactions included injection-site pain, redness, swelling or hardness, and underarm swelling or tenderness on the injection side. Systemic reactions included fever, headache, fatigue, muscle or joint pain, nausea or vomiting, and chills. Participants recorded reactions daily using electronic diaries.

This kind of endpoint is used to describe short-term reactogenicity: symptoms actively solicited during a defined period after vaccination. It differs from a count of all adverse events. The registry notes that not all solicited reactions were considered adverse events; investigators reviewed whether a solicited reaction should also be recorded as an adverse event. Serious and other adverse events are reported separately.

The outcome is a participant count, not a measure of symptom severity or duration. The posted results therefore describe how many participants had at least a solicited reaction, but do not by themselves describe the intensity, persistence, or clinical importance of each reaction. Nor do they establish that every reported reaction was caused by vaccination.

7. Results Posted in the Registry

• Licensed Inactivated Seasonal Influenza Vaccine: 46.7% (1400/2997) versus 75.7% (2283/3015) on control; risk difference -29.0 percentage points (95% CI -31.4 to -26.7), risk ratio 0.62 (0.59–0.64); unadjusted two-proportion z-test p = <0.001.

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.

Number of Participants With First Episode of RT-PCR Confirmed Modified United States (US) Centers for Disease Control and Prevention (CDC)-Defined ILI Caused by Any Influenza A or B Strains

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Licensed Inactivated Seasonal Influenza Vaccine: 1.4% (290/20124) versus 1.1% (223/20179) on control; risk difference 0.3 percentage points (95% CI 0.1 to 0.6), risk ratio 1.30 (1.10–1.55); unadjusted two-proportion z-test p = 0.003.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Licensed Inactivated Seasonal Influenza Vaccine than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The registry lists secondary outcomes covering additional definitions of RT-PCR-confirmed ILI, including illness with antigenic match to vaccine strains, as well as HAI antibody measures. These outcomes address different aspects of the study: clinical illness events, correspondence between circulating illness and vaccine strains, and measured immune response. They complement the short-term solicited-reaction outcome, but they do not measure the same construct.

The detailed results include a comparison for the first episode of modified CDC-defined ILI caused by any influenza A or B strains. The other listed secondary outcomes should not be assumed to have the same direction or strength of evidence based on that comparison. The registry record does not include detailed reported analyses for every listed secondary measure. In particular, the presence of an outcome in the registry is not itself evidence that a result was observed or that an analysis was posted.

Secondary outcomes can help characterize whether patterns are consistent across case definitions and immune measures, but they carry less confirmatory weight when many outcomes are examined and multiplicity handling is not reported. General explanation: testing many outcomes creates more opportunities for apparently notable results to occur by chance, so isolated unadjusted p-values need cautious interpretation. The registry record does not report a multiplicity strategy. The secondary findings therefore add context to the primary safety result, but should not be treated as a single definitive summary of efficacy, immunogenicity, and safety together.

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

• Number of Participants With First Episode of RT-PCR Confirmed Modified United States (US) Centers for Disease Control and Prevention (CDC)-Defined ILI Caused by Any Influenza A or B Strains
• Number of Participants With First Episode of RT-PCR-confirmed Protocol-defined ILI or Modified CDC-defined ILI Caused by Any Influenza A or B Strains With Antigenic Match to the Vaccine Strains
• Geometric Mean Titer (GMT) of Hemagglutination Inhibition (HAI)
• Number of Participants Reaching Seroconversion as Measured by HAI
• Number of Participants With an HAI Titer ≥1:40
• Geometric Mean Fold Rise (GMFR) of HAI Titers

9. Statistical Interpretation

10. Statistical Methods Explained

What does a risk difference describe?

For a binary outcome, each participant either has the recorded event or does not. The risk difference subtracts the event proportion in one group from the event proportion in the other, with the sign depending on the comparison’s stated ordering. General explanation: a difference near zero indicates similar observed proportions, while a difference farther from zero indicates a larger separation in the compared proportions. The sign must always be read alongside the group ordering and outcome definition.

For the primary comparison, the registry gives group proportions of 0.757 for mRNA-1010 and 0.467 for licensed vaccine. The risk difference is reported as -0.290 for licensed vaccine relative to mRNA-1010. For the secondary confirmed-ILI comparison, the group proportions are 0.011 and 0.014, respectively, and the risk difference is 0.003. These are unadjusted summaries; they do not account for other participant characteristics or design features beyond what is reflected in the posted comparison.

Why are relative measures also shown?

A risk ratio compares the event proportions by division, while an odds ratio compares the event odds. General explanation: these relative measures express separation on different scales from the absolute risk difference. They can be useful alongside an absolute difference, but their interpretation depends on the outcome frequency and the group ordering. A relative measure should not be treated as interchangeable with an absolute change in event probability. The registry reports relative measures for the posted comparisons, but the risk difference is the absolute-scale summary emphasized in the interpretation.

What does a confidence interval contribute?

General explanation: a confidence interval describes the range of estimates compatible with the observed data under the method used to construct it. It conveys precision as well as direction. A narrower interval indicates less statistical uncertainty around the estimate than a wider interval, but an interval does not eliminate possible bias, missing-data concerns, or uncertainty from outcome definitions. The registry reports intervals for the two comparisons discussed, but the method used to construct them is not reported in the registry record.

How should the p-values be read?

A p-value evaluates how compatible the observed data are with a specified null model, under the assumptions of the analysis. General explanation: a small p-value is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The primary comparison’s unadjusted p-value is <0.001, and the secondary confirmed-ILI comparison’s unadjusted p-value is 0.003. The record does not report an adjustment for testing multiple outcomes, so these values should be understood as unadjusted.

What do the outcome counts represent?

The primary outcome is a count of participants with one or more solicited reactions during the specified period; it is not a count of individual reaction episodes. The endpoint includes several local and systemic symptoms, and the registry does not report the separate result for each symptom in the primary outcome description. The secondary confirmed-ILI outcome counts participants with a first qualifying episode during its follow-up period. Because the endpoints use different event definitions and observation windows, their counts and proportions answer different questions.

Which populations are being compared?

The primary solicited safety set includes randomized participants who received any study vaccination and contributed solicited-reaction data, analyzed according to the vaccination actually received. The denominators in that outcome are 3015 and 2997. The secondary confirmed-ILI outcome uses denominators of 20180 and 20120. These populations and denominators differ; the registry record does not provide enough detail to reconcile them or describe all exclusions and missing-data handling. Results should therefore be read within each outcome’s own posted population rather than assuming a single analysis set applies to every endpoint.

Why do the methods not establish causation on their own?

Randomization is a design feature intended to support fair group comparisons, but interpretation still depends on how outcomes were measured, which participants contributed data, and how analyses were conducted. General explanation: blinding can reduce some risks of differential assessment, while active comparison places both groups against another vaccine rather than against no intervention. The registry describes the study as randomized and triple-masked, but detailed implementation, analysis adjustments, and missing-data procedures are not reported in the registry record. The posted estimates are thus best described as registry-reported group comparisons, with the stated limitations.

11. Confidence Intervals and Precision

The primary risk difference is -0.290, with a 95% confidence interval from -0.314 to -0.267. The interval lies on the negative side of zero under the registry’s comparison ordering, consistent with the lower posted solicited-reaction proportion in the licensed-vaccine group. Its endpoints are relatively close to the point estimate, indicating that the reported comparison is estimated with greater precision than one whose interval spans a wider range. Precision is not the same as freedom from bias or proof that a difference is clinically important.

For the secondary confirmed-ILI comparison, the risk difference is 0.003, with a 95% confidence interval from 0.001 to 0.005. The interval is above zero, in the direction of the larger posted event proportion in the licensed-vaccine group. Because this is a secondary endpoint, its interval should be considered alongside the outcome’s definition, analysis population, and the registry’s lack of reported multiplicity procedures.

General explanation: a confidence interval reflects sampling uncertainty under the calculation method; it does not account automatically for uncertainty from missing observations, measurement choices, unreported analysis decisions, or multiple testing. The registry record does not report the interval-construction method. The intervals therefore support a description of statistical precision for the posted comparisons, but cannot resolve those other sources of uncertainty.

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 figures are planning illustrations based on the observed effect, not the trial’s original design calculation. For these binary outcomes, the listed figures are participants per arm, rather than total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; each planning row uses the stated fraction of the observed effect to be detected. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the modeled number of participants per arm for a design with an 80% chance of detecting the specified effect under those assumptions, if that effect and model were correct. The 90% power column gives the corresponding planning number for a higher target chance of detection. These are design-planning quantities, not estimates of what the completed trial’s power was.

Each row asks what would be needed if the target effect were the full observed effect, or a smaller fraction of it. Smaller effects are harder to distinguish from random variation, so they require more participants under the same planning assumptions. The curve presents the same general planning relationship across effect sizes; it should be read as an illustration rather than as a reconstruction of the trial’s enrollment decision.

This is not observed power. It is a planning illustration computed from the observed effect, and it does not replace the study’s unreported original sample-size justification.

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 = 0.757; treatment proportion p₁ = 0.467; average p̄ = 0.612.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6891 = 1.3506.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6578 = 0.5537.
4. n = (1.3506 + 0.5537)² / (-0.2901)² = 43.1, rounded up to 44 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 <- 0.757213930348259                          # control proportion
p1 <- 0.467133800467134                          # 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(6602024)
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 = 44 (80% power), 58 (90% power)
 75% of observed effect: n per arm = 75 (80% power), 100 (90% power)
 50% of observed effect: n per arm = 160 (80% power), 214 (90% power)
power.prop.test: 43.1 
Simulated power at n = 44 per arm: 0.817 (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

The registry record does not report whether statistical testing across the primary and secondary outcomes was adjusted for multiplicity, whether any testing hierarchy was used, or whether some analyses were considered exploratory. The posted p-values are identified as unadjusted. Without a reported procedure, the degree to which the study controlled the chance of false-positive findings across its collection of outcomes cannot be established from the registry record.

Missing-data handling is also not reported in detail. For the primary solicited outcome, the registry defines the Solicited Safety Set as randomized participants who received any study vaccination and contributed solicited adverse-reaction data, analyzed according to vaccination actually received. This makes clear that contributing safety data is part of the population definition, but it does not explain how missing diary entries were treated or whether incomplete records were handled in another way. The registry record does not report a detailed missing-data analysis.

The posted denominators differ across the primary solicited-reaction outcome and the secondary confirmed-ILI outcome. The record gives the relevant denominators for each result, but does not fully explain the relationship between those analysis populations. It also does not report a detailed description of exclusions, protocol deviations, or other analysis-population rules for every endpoint.

These omissions limit assessment of the robustness of the posted comparisons. They do not change the reported estimates, but they make it harder to judge how sensitive the results might be to missing observations, analysis choices, or the number of outcomes tested. Those details are not reported in the registry record and should not be inferred.

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

Serious events with the highest arm-level rate: cerebrovascular accident (0.1%), atrial fibrillation (0.1%), chronic obstructive pulmonary disease (0.1%), prostate cancer (0.1%), cardiac failure congestive (0.1%).

The registry reports 455 participants with serious adverse events among 20350 at risk in the mRNA-1010 group and 392 among 20353 at risk in the licensed-vaccine group. It reports zero participants with other, nonserious adverse events in each group’s posted count. Deaths are listed separately as 40 and 34. These counts should be read as registry-reported safety summaries, not as evidence that a particular event was caused by a study vaccine.

The most frequently listed serious-event terms each have a reported frequency of 0.1%: cerebrovascular accident, atrial fibrillation, chronic obstructive pulmonary disease, prostate cancer, congestive cardiac failure, and death. The registry does not provide enough information in these summaries to assess timing, individual clinical context, or causal attribution. The serious adverse-event counts also differ in scope from the solicited local and systemic reactions recorded through Day 7; they are separate safety summaries.

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

The posted results describe two different questions. The primary outcome compares the number of participants with solicited local or systemic reactions from Day 1 up to Day 7. The secondary confirmed-ILI outcome compares the number with a first qualifying illness episode during a longer follow-up period. Their event definitions, follow-up windows, and analysis denominators differ, so one should not be used as a proxy for the other.

The primary comparison shows a lower recorded proportion of solicited reactions in the licensed-vaccine group than in the mRNA-1010 group, with a confidence interval that remains on the same side of zero under the registry’s comparison ordering. This describes the posted short-term reaction data. It does not establish the severity or duration of reactions, explain their cause, or summarize all safety outcomes.

The secondary confirmed-ILI comparison is a separate result. It is one of several listed secondary outcomes, and the registry record does not report detailed analyses for every listed endpoint. The absence of reported detail for other outcomes should not be interpreted as a null result. Likewise, the listed antibody outcomes measure immune responses and are not interchangeable with clinical illness outcomes.

General explanation: randomized comparisons can support inference about group differences, but an estimate remains tied to its outcome definition, population, follow-up, and analysis. Unadjusted secondary p-values warrant particular care when multiplicity procedures are not reported. The registry record does not report enough information to determine how all potential sources of missingness or analysis choices were handled.

These results alone do not establish an overall balance of benefits and harms, nor do they justify a treatment recommendation. They provide registry-reported comparisons for specified outcomes in adults ≥50 years of age. Interpretation beyond those outcomes or that population would require evidence not reported in the registry record.

17. Why This Trial Matters Statistically

This trial is statistically informative because it places a candidate seasonal influenza vaccine against licensed active comparators in a randomized, parallel-group Phase 3 design. The registry also identifies triple masking. These design features are relevant to how group differences can be interpreted, while the active comparator makes the central comparison one vaccine strategy versus another rather than vaccination versus no vaccination.

The posted outcomes illustrate why endpoint choice matters. Short-term solicited reactions are actively collected symptom reports, whereas confirmed ILI is a clinical event outcome defined by symptoms and RT-PCR confirmation. HAI measures address immune response. They capture different dimensions, so conclusions should be anchored to the endpoint being analyzed rather than combined into a single undifferentiated result.

The registry’s estimates also demonstrate the complementary roles of absolute differences, confidence intervals, and p-values. The difference describes the scale and direction of a group contrast; the interval conveys statistical precision; and the p-value is a test summary under the analysis assumptions. None alone establishes clinical importance, causality, or consistency across all outcomes.

Finally, the registry record contains meaningful limits on what can be evaluated statistically. It does not report the original sample-size justification, detailed missing-data methods, or multiplicity procedures. These omissions make careful separation of posted results from broader claims especially important. The trial’s scale and phase do not remove the need to interpret each result in light of its population, endpoint, and analysis details.

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.

The primary outcome is a composite count of participants with solicited reactions, not a symptom-by-symptom analysis in the posted summary. It covers a short period from Day 1 up to Day 7 and does not capture, in that endpoint, the complete range of later adverse events. The registry explicitly notes that not every solicited reaction was considered an adverse event.

The active comparator includes TIV or QIV products, with several licensed products named. The registry record does not state how many participants received each product or provide product-specific comparisons. This means the posted comparator result is not a separate estimate for each named vaccine.

The efficacy-related secondary outcome reported in detail uses a modified CDC-defined ILI definition and RT-PCR confirmation. Other listed outcomes use distinct definitions or measure HAI responses. The results are therefore specific to the stated endpoint definitions and should not be generalized automatically to all influenza illness or all immune outcomes. Follow-up for the secondary outcome is described as beginning on Day 14 and extending to the end of influenza season, up to 7.5 months.

The registry record does not report the original sample-size rationale, multiplicity handling, detailed missing-data procedures, or full statistical analysis plan. It also does not explain in detail how the different analysis denominators relate. Those limits constrain assessment of robustness and prevent reconstruction of unreported analyses. The record’s population is adults ≥50 years of age, so the reported comparisons do not directly describe other age groups.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: A Study of mRNA-1010 Compared With a Licensed Influenza Vaccine in Adults ≥50 Years of Age — NCT06602024.
• Registry record last updated 2026-09-16; status last verified 2026-08.
• Results first posted 2026-09-16.
• 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

NCT06602024 is a completed randomized, observer-blind, active-controlled, parallel-group Phase 3 study of mRNA-1010 versus licensed inactivated seasonal influenza vaccines in adults ≥50 years of age. Enrollment was 40805. The primary posted outcome counts participants with solicited local or systemic adverse reactions from Day 1 up to Day 7.

The registry reports a primary risk difference of -0.290 (95% confidence interval -0.314 to -0.267; unadjusted p <0.001) for the stated comparison, and a secondary confirmed-ILI risk difference of 0.003 (95% confidence interval 0.001 to 0.005; unadjusted p=0.003). The registry record does not report the original sample-size justification, detailed missing-data methods, or multiplicity procedures.