A Study to Evaluate the Safety and Immunogenicity of mRNA-1975 and mRNA-1982 Against Lyme Disease in Participants 18 Through 70 Years of Age: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Safety and Immunogenicity of mRNA-1975 and mRNA-1982 Against Lyme Disease in Participants 18 Through 70 Years of Age (NCT05975099), a randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection.

2. Clinical Question

The trial also evaluated immunogenicity. The listed secondary outcomes include geometric mean concentrations of antibodies against outer surface protein A for multiple serotypes, measured by ELISA, and a geometric mean fold rise for the SR-1 antigen. The results centre on the posted primary safety outcome; the reaction counts do not answer the antibody questions.

The primary endpoint is a count of participants with at least one solicited reaction during the specified period. It is not a count of all reaction episodes, nor does it describe reaction severity or duration. The registry record notes that not all solicited reactions were considered adverse events: an investigator reviewed whether a solicited reaction should also be recorded as an adverse event.

3. Trial Design

The registry record describes a completed Phase 1/2, randomized, observer-blind, placebo-controlled, dose-ranging study conducted in parallel. Its official title describes the vaccines as heptavalent mRNA-1975 and monovalent mRNA-1982. The record lists double masking. These descriptions establish the broad design, but details about who was masked and how masking was maintained are not reported in the registry record.

The study enrolled 807 participants and evaluated the two vaccine candidates in separate dose groups alongside placebo. There were four mRNA-1975 dose levels and three mRNA-1982 dose levels. Participants in the vaccine groups were scheduled to receive 3 intramuscular injections on Days 1, 57, and 169; the placebo schedule used the same injection days. The posted primary outcome is specifically tied to the first injection, rather than the later injections.

The study start date was 2023-07-26, the primary completion date was 2025-05-30, and the registry status is completed. Those dates describe the registry record; they do not, by themselves, establish when every participant completed follow-up or when each analysis was conducted.

For the primary endpoint, the posted analysis population is the First Injection Solicited Safety Set. It included randomly assigned participants who received study vaccine and contributed any solicited reaction data. The record gives group-specific denominators for this outcome, which can differ across arms. Further details about allocation procedures, any stratification, the planned analysis model, and the original sample-size rationale are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

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: The First Injection Solicited Safety Set included all randomly assigned participants who received the study vaccine and contributed any solicited AR 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: The Full Analysis Set included all randomly assigned participants who received the study injection.

Only the first 6 of 9 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Solicited Local and Systemic Adverse Reactions (ARs) Within 7 Days After Day 1 Injection, measured over Up to 7 days after Day 1 injection.

The primary endpoint counts participants with solicited local or systemic adverse reactions within 7 days after the Day 1 injection. 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 pain, joint pain, nausea or vomiting, and chills. The record says these reactions were collected in an electronic diary.

This endpoint is used to summarize short-term reactions that the study specifically asked participants to report. Counting participants with a reaction gives a straightforward binary outcome for each person: a participant either met the endpoint during the stated period or did not. The count does not show how many different symptoms an individual reported, how often a symptom occurred, or how intense or long-lasting it was.

The endpoint is also distinct from the broader adverse-event summaries. The registry record notes that not all solicited reactions were considered adverse events; investigators reviewed whether a solicited reaction should also be recorded as an adverse event. The seven-day window is limited to the period after the first injection. This primary endpoint therefore does not, on its own, summarize reactions after the later injections or establish the full safety profile over the study.

7. Results Posted in the Registry

• mRNA-1975 Dose Level 1: 70.0% (70/100) versus 32.7% (33/101) on control; risk difference 37.3 percentage points (95% CI 24.5 to 50.1), risk ratio 2.14 (1.57–2.92); unadjusted two-proportion z-test p = <0.001.
• mRNA-1975 Dose Level 2: 79.2% (80/101) versus 32.7% (33/101) on control; risk difference 46.5 percentage points (95% CI 34.4 to 58.6), risk ratio 2.42 (1.80–3.26); unadjusted two-proportion z-test p = <0.001.
• mRNA-1975 Dose Level 3: 82.8% (82/99) versus 32.7% (33/101) on control; risk difference 50.2 percentage points (95% CI 38.4 to 61.9), risk ratio 2.54 (1.89–3.40); unadjusted two-proportion z-test p = <0.001.
• mRNA-1975 Dose Level 4: 89.2% (91/102) versus 32.7% (33/101) on control; risk difference 56.5 percentage points (95% CI 45.6 to 67.5), risk ratio 2.73 (2.05–3.64); unadjusted two-proportion z-test p = <0.001.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level. Each participant in the relevant safety set either had one or more solicited reactions during the stated window or did not. The posted group counts and denominators describe how frequently participants met that definition in each arm. They are not counts of symptoms, episodes, or all adverse events.

What the risk difference describes

The comparison table uses a risk difference for each vaccine dose group versus placebo. In general, a risk difference subtracts the event proportion in the comparator group from the event proportion in the treatment group. It is expressed on the probability scale, so it describes the absolute separation between the two group event frequencies. Here, a positive posted risk difference corresponds to a higher observed frequency of the solicited-reaction endpoint in the vaccine group than in placebo.

This is an unadjusted comparison as presented in the registry record. The point estimate summarizes the observed contrast, while its confidence interval describes the range of values compatible with the data under the method used. The precise statistical method used to calculate the intervals is not reported in the registry record. The ratio measures also shown in the comparison data are relative measures; they answer a different question from the absolute risk difference. The plotted and tabulated results should therefore be read on the scale each display identifies.

How to read the p-values

A p-value is a measure of how compatible the observed data are with a stated null model, under the assumptions of the analysis. It is not the probability that the null hypothesis is true, and it does not measure the size or importance of a difference. The record posts unadjusted p-values of < 0.001 for each of the seven vaccine-versus-placebo comparisons. Because they are unadjusted, they do not account for the fact that the record presents multiple dose comparisons. The registry record does not report a multiplicity strategy for the primary comparisons.

The endpoint is a count of participants with an event, rather than a continuous measurement such as an antibody concentration. Methods appropriate for continuous outcomes cannot automatically be assumed. The specific model or test used by the sponsor is not reported in the registry record. The comparison estimates and p-values should therefore be described as posted, without attributing them to an unreported regression model, continuity correction, or other procedure.

Why the endpoint definition matters

The event definition combines local and systemic symptoms, and a participant counts as meeting the endpoint if they have a solicited reaction in the period. That combined outcome is useful as a summary, but it can conceal differences among the symptoms. For example, the total count does not show whether a group’s participants reported primarily local reactions, systemic reactions, or both. The record lists the specific symptoms collected, but the primary result is the participant count for the combined endpoint.

The safety population also matters. The record defines the First Injection Solicited Safety Set as randomly assigned participants who received study vaccine and contributed any solicited reaction data. A participant without contributed reaction data is not necessarily equivalent to a participant who reported no reaction. The record does not describe the method used to handle missing diary entries or incomplete observation windows. The posted arm denominators should be interpreted in light of the stated safety-set definition rather than assumed to include every randomized participant.

Planning calculations are not trial results

The sample-size illustrations use a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. They use the observed effect or a stated fraction of that observed effect as the effect to detect. These are planning calculations, not the original trial design rationale. The record does not report the assumptions or calculations used to choose the trial’s enrollment target.

In general, over-dispersion matters when observed variability exceeds what a chosen statistical model expects; a model that ignores it can misstate uncertainty. The posted primary result is a binary participant count, but the registry record does not identify a model or report an over-dispersion assessment. It would not be appropriate to claim that over-dispersion was tested, or that a particular model accounted for it, based on the information in the registry record.

10. Confidence Intervals and Precision

The confidence intervals in the comparison display are important because a point estimate alone does not show how much uncertainty remains. In general, a confidence interval gives a range of estimates compatible with the observed data under the method and assumptions used. It is not a range that contains a fixed proportion of individual participants’ reactions, and it does not establish that every value inside the interval is equally plausible.

For this outcome, each interval belongs to a vaccine-dose versus placebo risk difference. The display makes it possible to see the direction and precision of each absolute contrast. Wider intervals indicate less precision than narrower intervals. Precision depends on the amount and pattern of information in the groups, as well as the statistical method. The group denominators are around one hundred participants per arm, but the registry record does not report a precision target for the original design.

All seven posted point estimates are above zero, and the listed confidence intervals in the comparison table are also on the positive side. The posted unadjusted p-values are < 0.001. This describes the individual comparisons as posted; it does not resolve uncertainty about the analysis method or the effect of considering multiple comparisons together. The intervals are not adjusted for multiplicity in the displayed data, and whether the sponsor used another inferential approach is not reported in the registry record.

Precision also has a substantive limit: the primary measure combines several solicited symptoms into a single participant-level outcome. A precise estimate for that combined endpoint would not provide equally precise estimates for each symptom, reaction severity, or later follow-up period. Those are different quantities. The confidence intervals should be read as uncertainty about the defined first-injection reaction contrast, not as a summary of every safety or immunogenicity question in the trial.

11. 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 its accompanying plot are planning illustrations based on the observed effect, not the trial’s original design calculation. For this binary endpoint, the figures are participants per arm, not total events. The planning assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The table considers the full observed effect and fractions of that effect. The original trial’s sample-size justification and design assumptions are not reported in the registry record.

The column for 80% power gives the participants per arm estimated to be needed, under those assumptions, to detect the effect specified in a row with 80% power. The 90% power column gives the corresponding per-arm planning figure for 90% power. In general, power describes the chance that a study would detect an effect of the size assumed if that effect were present and the planning assumptions held. These table values are not observed power.

Rows that assume a smaller fraction of the observed effect require more participants per arm than rows based on the full observed effect. For example, planning for 75% of the observed effect requires 49 participants per arm for 80% power for the mRNA-1975 Dose Level 1 comparison; planning for 50% of that observed effect requires 109 participants per arm. The plot visualizes the same relationship between the assumed effect and the planning requirement. Its curve is a display of the planning calculation, not a record of participant outcomes or a separate estimate of treatment effect.

These illustrations are sensitive to the observed effect used as their starting point. They should not be treated as proof that the completed trial was adequately or inadequately powered for its original objectives. The record does not report the sponsor’s original sample-size assumptions, and the planning display does not replace that missing design information.

12. 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 = 0.327; treatment proportion p₁ = 0.700; average p̄ = 0.513.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.7069 = 1.3854.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6557 = 0.5519.
4. n = (1.3854 + 0.5519)² / (0.3733)² = 26.9, rounded up to 27 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 <- 0.326732673267327                          # control proportion
p1 <- 0.7                          # 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(5975099)
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 = 27 (80% power), 36 (90% power)
 75% of observed effect: n per arm = 49 (80% power), 65 (90% power)
 50% of observed effect: n per arm = 109 (80% power), 145 (90% power)
power.prop.test: 26.9 
Simulated power at n = 27 per arm: 0.778 (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.

13. Multiplicity, Missing Data and Analysis Populations

The comparison display contains seven vaccine-dose versus placebo contrasts for the primary solicited-reaction endpoint. Each is accompanied by an unadjusted p-value. When several hypotheses are tested, the chance of at least one false positive across the set can differ from the error rate for one test alone. Statistical approaches to this issue can include prespecified testing sequences or adjustments, but the choice depends on the trial’s objectives and analysis plan. A multiplicity procedure for these comparisons is not reported in the registry record.

The registry record lists 20 outcome measures and 14 posted secondary results. Secondary outcomes include antibody concentration measures for several serotypes and a fold-rise measure. The endpoint list indicates that the trial examined more than the primary safety question, but the available information does not establish how these measures were prioritized, whether they were tested confirmatorily, or how multiplicity across them was addressed. Those details are not reported in the registry record.

Missing-data handling is also not reported in the registry record. The primary safety set requires contributed solicited reaction data, but the record does not explain how incomplete eDiary entries, missed observation days, or other missing values were handled. It is therefore not possible to assess from this record whether missingness was assumed to be unrelated to reaction status or handled through an imputation or sensitivity analysis.

The analysis population is defined for the primary endpoint as participants who were randomly assigned, received study vaccine, and contributed solicited reaction data. A complete description of all analysis populations, including those used for immunogenicity outcomes, is not reported in the registry record. Nor are the detailed statistical methods, prespecified analysis hierarchy, or protocol-level deviations. These gaps limit assessment of how the posted comparisons relate to the full prespecified analysis plan.

14. 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: urinary tract infection (2.0%), appendicitis (1.0%), covid-19 (1.0%), rhinovirus infection (1.0%), plasma cell myeloma (1.0%).

The serious adverse event display reports the number of participants with serious adverse events and the number at risk in each arm. In order across mRNA-1975 Dose Levels 1 through 4, the counts were 4 of 100, 4 of 101, 6 of 99, and 4 of 102 participants. For mRNA-1982 Dose Levels 1 through 3, the counts were 6 of 98, 3 of 100, and 4 of 105; for placebo, the count was 7 of 101. These are participant counts, not a comparison adjusted for follow-up time or other factors.

The record separately lists deaths: 1 in mRNA-1975 Dose Level 2, 1 in mRNA-1975 Dose Level 4, 1 in mRNA-1982 Dose Level 2, and 1 in placebo; the other groups have none listed. The most frequently listed serious-event term is urinary tract infection at 2.0%; the other displayed terms are each listed at 1.0%. These summaries do not establish causality. The registry record does not provide a basis for attributing an individual event or death to a study intervention.

Serious adverse events are distinct from solicited reactions in the primary endpoint. They are not interchangeable measures, and the short post-injection reaction counts should not be read as a summary of the serious-event data. The displayed counts also do not, by themselves, provide a complete account of event timing, duration, relatedness, or clinical course.

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

The posted primary results show that more participants in each vaccine dose group than in placebo met the definition of a solicited local or systemic reaction within 7 days after the first injection. The comparison estimates and intervals describe the size and uncertainty of those vaccine-versus-placebo contrasts on the risk-difference scale. The unadjusted p-values are reported as < 0.001 for each comparison. Taken together, these are findings about a defined short-term safety outcome in this trial population.

They do not show that either vaccine candidate prevents Lyme disease. The primary endpoint is a reaction count, not a disease endpoint. Nor do these results establish the magnitude or persistence of antibody responses, despite immunogenicity being a stated study objective. Those questions require the relevant immunogenicity results and, for prevention, evidence based on disease outcomes.

The counts do not describe how severe, burdensome, or long-lasting the reactions were, and they combine local and systemic symptoms. They also concern the period after the first injection, rather than the full injection schedule. The record notes a separate review of whether solicited reactions were also to be recorded as adverse events, so the primary count should not be treated as equivalent to the broader adverse-event summaries.

The available results also do not settle comparisons among dose levels. The posted contrasts are each against placebo, not direct comparisons between vaccine doses. The observed pattern across groups is descriptive; a formal dose-trend analysis is not reported in the registry record. In addition, the listed p-values are unadjusted, and a multiplicity strategy is not reported. The results should therefore be interpreted as evidence about the posted comparisons and endpoint, without extending them to unreported analyses or broader clinical claims.

16. Why This Trial Matters Statistically

This trial illustrates why endpoint definition matters in safety analyses. The primary outcome is not a general judgment of safety; it is a count of participants with a specified set of solicited symptoms during a defined period after the first injection. That precise framing makes the result interpretable, while also making its limits visible. The counts cannot answer questions about other symptoms, severity, duration, or events outside that window.

The design includes multiple dose groups for two candidates, each compared with a shared placebo group. That structure creates several meaningful contrasts, but it also makes multiplicity and the choice of analysis hierarchy important. The record posts unadjusted comparisons and does not report a multiplicity plan. A statistical reader should therefore distinguish the individual estimates from any broader claim across all dose groups or outcomes.

The confidence intervals complement the event counts and p-values by showing uncertainty around the estimated contrasts. Their interpretation depends on the statistical method, which is not reported in the registry record. The planning table and plot provide another useful teaching point: planning requirements depend on the effect size assumed, and smaller target effects require more participants under the stated planning assumptions. These illustrations do not reveal the original rationale for enrollment.

Finally, the trial’s safety and immunogenicity objectives are related but distinct. A short-term solicited-reaction endpoint cannot stand in for antibody measures or disease prevention. Keeping the endpoint, comparison, analysis population, and question aligned is central to interpreting the posted evidence without overextending it.

17. 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 result covers solicited reactions within 7 days after the first injection. It does not summarize reactions after the injections on Days 57 and 169, or the entire period of study follow-up. Although the record lists the symptoms collected, the displayed primary result combines local and systemic reactions, so it does not show which symptoms account for the group counts.

The primary analysis population includes participants who received study vaccine and contributed solicited reaction data. The record does not explain how missing diary data were handled, or whether participants with incomplete reporting were treated in a particular way. Group denominators differ, and the reason for each difference is not reported.

The record does not report the sponsor’s original sample-size justification, detailed statistical model, or method for constructing the confidence intervals. It also does not report a multiplicity strategy for the several primary comparisons or the secondary outcomes. As a result, the posted unadjusted p-values should not be mistaken for adjusted family-wise conclusions.

The displayed comparisons are against placebo, not direct tests between dose levels. A formal dose-response analysis is not reported. The primary endpoint also does not assess Lyme disease incidence or establish the clinical meaning of antibody responses. Finally, although serious adverse event counts and deaths are listed, these summaries do not supply event-level timing, attribution, or clinical narratives. Each limitation narrows the conclusions that can be drawn from this record.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: A Study to Evaluate the Safety and Immunogenicity of mRNA-1975 and mRNA-1982 Against Lyme Disease in Participants 18 Through 70 Years of Age — NCT05975099.
• Registry record last updated 2026-07-30; status last verified 2026-07.
• Results first posted 2026-07-30.
• 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.

21. Record Summary

This completed, randomized, placebo-controlled Phase 1/2 study enrolled 807 healthy participants 18 through 70 years of age. It evaluated four dose levels of mRNA-1975 and three dose levels of mRNA-1982, alongside placebo, with 3 intramuscular injections scheduled on Days 1, 57, and 169.

The primary posted outcome counted participants with solicited local or systemic adverse reactions within 7 days after the first injection. Counts were higher in each vaccine dose group than in placebo, and each posted unadjusted vaccine-versus-placebo comparison had a p-value of < 0.001. The record also posts serious adverse event summaries and secondary immunogenicity results. It does not report the original sample-size rationale, detailed statistical methods, missing-data handling, or multiplicity strategy.