Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults (NCT05219968), a randomized phase 3 study. The primary outcome is Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps..

2. Clinical Question

The clinical question is about a group-level difference in change on a symptom scale, not whether every participant experienced the same course. Lower 3CS scores indicate fewer or less severe symptoms, and the registry defines the composite as the sum of the three symptom scores. The endpoint and population are narrower than the overall adult chronic rhinosinusitis population: the primary result is specifically for participants without nasal polyps. The record gives summary statistics for the two groups and a recalculation of their unadjusted mean difference. It does not report a sponsor analysis for this endpoint in the posted analysis fields, so the displayed recalculation should be read as an unadjusted comparison of the posted summaries rather than as an adjusted trial analysis.

3. Trial Design

ENLIGHTEN 1 was a phase III, randomized, blinded, controlled, parallel-group trial of LYR-210 for chronic rhinosinusitis in adults. The registry record describes the trial as multicenter and lists double masking. Its status is completed. The recorded study start is 2022-01-27 and the primary completion date is 2024-03-04. Enrollment is reported as 196.

The intervention arm is described as receiving a single administration of LYR-210 drug matrix (7500 μg); the sham control arm is described as receiving a single mock administration procedure. Background therapy is listed among the interventions, but the record does not explain its use by arm. The brief summary also describes a safety extension phase with crossover or continued treatment. Extension group labels include LYR-210-LYR-210, LYR-210-Sham, and Sham-LYR-210. The posted summaries do not establish how participants entered each extension group or provide enough detail to treat those groups as a randomized comparison of the original interventions.

The primary endpoint is reported for an ITT Analysis Set without nasal polyps, with 101 participants in the LYR-210 group and 54 in the sham group in that endpoint summary. These analysis-set counts differ from the enrollment figure and are not a substitute for a complete account of participant flow. Reasons for the analysis-set composition, withdrawals, and missing endpoint observations are not reported in the registry record. The planned sample-size justification, allocation procedure, and detailed masking procedures are also not reported in the registry record. The registry record does not describe the trial's original power assumptions or statistical analysis plan, so those should not be inferred from the posted group summaries.

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.

Week 24 Treatment Period

Reasons for not completing this period:

Safety Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT Analysis Set Without Nasal Polyps

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: ITT Analysis Set

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline (CFBL) in the 7-day Average Composite Score of 3 Cardinal Symptoms (3CS) in Participants Without Nasal Polyps., measured over 24 Weeks.

The primary endpoint is change from baseline in the 7-day average composite score of three cardinal symptoms at 24 weeks, among participants without nasal polyps. The three symptoms are nasal blockage, obstruction, or congestion; anterior or posterior nasal discharge; and facial pain or pressure. Participants recorded symptoms daily in a diary. Each symptom was rated on a 0–3 scale, from none or absent to severe, and the composite is the sum of the three symptom scores. The total ranges from 0–9, with higher scores indicating worse symptoms.

Change from baseline expresses how the average score at the stated follow-up differs from the participant's baseline score. A negative group mean change therefore represents a decrease in symptom score over the period. Comparing mean changes between randomized groups provides a summary of the difference in their average observed changes, while preserving the endpoint's original scale. It does not show the distribution of individual responses or how many participants improved by a particular amount.

A daily symptom diary uses repeated reports rather than relying on a single recollection at the end of follow-up. Averaging across seven days is intended to summarize symptoms over a week, rather than a single day's rating. This endpoint is used to represent symptom burden in the specified population and timeframe. The registry record does not report a threshold for a clinically important change, so the numerical difference should not be labeled clinically meaningful or unmeaningful on the basis of the posted record alone.

7. Results Posted in the Registry

• LYR-210: mean -2.13 versus -2.06 on control; difference -0.07 (95% CI -0.78 to 0.64), standardized effect d = -0.03; z-test p = 0.847.

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.

CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24.

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • LYR-210: mean -2.35 versus -1.83 on control; difference -0.52 (95% CI -1.17 to 0.13), standardized effect d = -0.23; z-test p = 0.115.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between LYR-210 and the control. The interval gives the range of effects that remain compatible with the data.

CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • LYR-210: mean -19.70 versus -15.70 on control; difference -4.00 (95% CI -9.88 to 1.88), standardized effect d = -0.19; z-test p = 0.182.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between LYR-210 and the control. The interval gives the range of effects that remain compatible with the data.

CFBL in the 3-D Volumetric CT Score at Week 20

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • LYR-210: mean -2.71 versus -0.28 on control; difference -2.43 (95% CI -5.51 to 0.65), standardized effect d = -0.23; z-test p = 0.123.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between LYR-210 and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary outcomes include symptom change in all participants, change in SNOT-22 total score, and change in a 3-D volumetric CT score. Their point estimates all have a direction favoring a greater average decrease in the LYR-210 group than in the sham group, while their confidence intervals include no difference. The pattern is broadly aligned in direction with the primary estimate, but the secondary comparisons do not provide a clear, precise separation between groups in these unadjusted recalculations.

These outcomes measure different aspects of chronic rhinosinusitis. The symptom composite covers the three cardinal symptoms; SNOT-22 is a broader patient-reported total score; and the CT endpoint is reported as percent ethmoid opacification. Their scales and timeframes differ, so numerical estimates should not be compared as though they were measurements in the same units. The registry lists rescue treatments for CRS through Week 24 as a secondary outcome, but a result for that outcome is not reported in the registry record.

Unadjusted secondary results carry less weight than a prespecified primary comparison for several reasons. A trial can evaluate multiple outcomes, timepoints, and populations; considering many comparisons increases the chance that an apparently notable result arises by chance. The registry record does not report a multiplicity adjustment or a hierarchy for testing these endpoints. The recalculated secondary p-values therefore should not be read as confirmatory evidence independent of the primary result. In addition, the registry's reported analyses are empty for the secondary outcomes, so the comparisons are unadjusted recalculations from posted summaries rather than sponsor-reported model results.

The secondary pattern can add context about whether different kinds of measures move in similar directions, but it cannot substitute for missing analysis details or establish a treatment effect. The posted estimates, intervals, and unadjusted p-values should be considered together, with attention to the endpoints' differing meanings and the absence of reported multiplicity procedures.

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

• CFBL in the 7-day Average Composite Score of 3CS in All Participants at Week 24.
• CFBL in the 22-item Sino-Nasal Outcome Test (SNOT-22) Total Score at Week 24
• CFBL in the 3-D Volumetric CT Score at Week 20
• Participants With Rescue Treatments for CRS Through Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

The statistical summaries describe continuous outcomes as group means and standard deviations. The primary 3CS score is a continuous measure: it can take values across a numeric range, and its group mean summarizes the average score change. A mean is useful for expressing the center of a distribution in the measure's original units. It can, however, conceal variation in individual scores, including participants whose changes differ substantially from the group average.

What does a mean difference represent?

The primary contrast is the mean change in the LYR-210 group minus the mean change in the sham control group. The recalculated estimate is -0.07 score points. A negative value means the LYR-210 group's average change was more negative, and thus a somewhat larger average decrease, than the sham group's average change. This direction follows from the score definition: higher scores indicate worse symptoms. The estimate is an unadjusted comparison based on the posted group summaries, not a model-adjusted effect.

Randomization is intended to make treatment groups comparable in expectation, but it does not guarantee that every observed characteristic is balanced in a particular trial. An adjusted analysis may account for baseline values or other prespecified factors, but the registry record does not report whether such adjustment was used for the primary endpoint. The posted summary comparison should therefore not be mistaken for a complete account of the trial's planned analysis.

What does the standard deviation describe?

A standard deviation describes the spread of participant measurements around their group mean. The primary standard deviations are 2.172 for LYR-210 and 2.136 for sham. In general, a larger standard deviation indicates greater dispersion of observations around the mean, although the interpretation depends on the scale and distribution. The standard deviation is not the standard error of the mean, and it is not a confidence interval. It describes participant-level variation rather than the precision of the estimated group average.

For a comparison of group means, the standard error reflects uncertainty in the estimated difference. It depends on within-group variability and the number of observations contributing to each group summary. A confidence interval is constructed around the estimate to express a range of values compatible with the data under the method's assumptions. The comparison reported in this analysis uses a recalculation from the posted summary statistics. It does not incorporate adjustment or additional information that might be present in a trial-level analysis.

Why pay attention to the scale?

The symptom composite adds the three cardinal symptom ratings, each recorded from 0 to 3. The total score ranges from 0–9, and higher scores represent worse symptoms. A change is interpreted in score points, not as a percentage or a change in the number of participants. In general, keeping a result on the original scale makes it easier to connect a mean difference to the measurement, but judging whether a difference matters to patients requires context such as a validated meaningful-change threshold. Such a threshold is not reported in the registry record.

Over-dispersion is a concern in some statistical models for count data when variability exceeds what the model assumes. The primary endpoint is reported as a continuous score with means and standard deviations, not as a count outcome. That count-model issue is therefore not the principal interpretive concern for these posted summaries. More relevant considerations include the distribution of score changes, missing observations, baseline adjustment, and the handling of repeated diary entries. The registry record does not report diagnostic assessments or detailed modeling choices for these matters.

What does the p-value add?

The unadjusted p-value for the recalculated primary comparison is 0.847. In general, a p-value measures how unusual data at least as discrepant as those observed would be under a specified null model and its assumptions. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The registry record does not report a multiplicity adjustment or a sponsor-reported inferential analysis alongside this comparison. The p-value should thus be read as part of the unadjusted recalculation, not as a stand-alone verdict about the trial.

More broadly, the record's analysis detail is limited. The primary population is identified as an ITT Analysis Set without nasal polyps, but the precise handling of missing diary data, deviations from assigned treatment, and incomplete follow-up is not reported in the registry record. The study design is randomized and double masked, yet the allocation method and masking procedures are not specified. Those details matter because statistical estimates rely on assumptions about who contributes data, how outcomes are measured, and how comparisons are made. Where the record does not describe these methods, the posted summary cannot resolve their influence.

11. Confidence Intervals and Precision

The primary recalculated mean difference is -0.07 score points, with a 95% confidence interval that crosses zero. This interval is important because it communicates uncertainty about the estimated contrast, rather than treating -0.07 as an exact or definitive value. Its negative and positive limits allow for a difference favoring either group under the calculation. The unadjusted p-value of 0.847 is consistent with the interval's inclusion of no mean difference.

Precision depends on the amount of information in the comparison and the variability of the outcome. The primary summaries include 101 participants in the LYR-210 group and 54 in the sham group, with standard deviations of 2.172 and 2.136. These values give context for the recalculation, but they do not remove uncertainty. The group means are similar, and the confidence interval is the relevant summary of how uncertain the estimated difference remains.

In general, a confidence interval is not a range containing a fixed proportion of individual participant outcomes. It is an interval procedure for estimating a population quantity; under its assumptions, intervals constructed repeatedly would cover the true quantity at the stated rate. It also does not show which values are clinically important. The registry record does not report a meaningful-change threshold for the 3CS scale, so statistical uncertainty cannot be translated into a judgment about clinical importance from this record alone.

The interval is a recalculation from posted summary statistics, not necessarily the interval from the trial's planned primary analysis. The registry record does not provide a sponsor-reported primary confidence interval or explain whether the official analysis adjusted for baseline or handled missing observations differently. The available interval therefore characterizes this unadjusted calculation, not every plausible analysis of the trial.

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 planning figures are participants per arm for the continuous-outcome comparisons in this trial. They are not total event counts. The planning illustration uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It sets the effect to detect at a stated fraction of the observed effect. The original design assumptions and sample-size justification are not reported in the registry record.

The 80% power column gives the estimated participants per arm for a hypothetical study to have an 80% chance of detecting the specified effect under those planning assumptions, if that effect is the true effect and the model assumptions hold. The 90% power column gives the corresponding planning figure for a 90% chance. These are design probabilities under a hypothetical alternative, not probabilities that the trial result is correct. This is not observed power.

For the primary endpoint, planning for 100% of the observed effect gives 14,942 participants per arm for 80% power and 20,003 participants per arm for 90% power. Planning for 75% of the observed effect gives 26,563 participants per arm for 80% power and 35,560 participants per arm for 90% power. Planning for 50% of the observed effect gives 59,766 participants per arm for 80% power and 80,009 participants per arm for 90% power. The observed primary mean difference is close to zero, so basing a hypothetical design on a fraction of that estimate produces very large planning figures.

Smaller effects require more participants to distinguish them from random variation at the same power and significance level. These calculations are illustrations derived from the observed effect, not evidence that the completed trial had adequate or inadequate power under its original plan. The registry record does not report the trial's original target, anticipated effect, or other design assumptions. The planning values should not be treated as recommended sample sizes without a design tailored to a future research question.

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, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.070; pooled standard deviation σ = 2.160.
2. n = 2 × (1.96 + 0.842)² × 2.160² / -0.070² = 14,941.3, rounded up to 14,942 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
delta <- -0.0699999999999998                      # observed difference in means
sigma <- 2.15959734809116                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^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 (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5219968)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 14,942 (80% power), 20,003 (90% power)
 75% of observed effect: n per arm = 26,563 (80% power), 35,560 (90% power)
 50% of observed effect: n per arm = 59,766 (80% power), 80,009 (90% power)
power.t.test: 14942.2 
Simulated power at n = 14,942 per arm: 0.802 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-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 how the trial handled multiplicity. Multiplicity arises when a study evaluates more than one outcome, timepoint, subgroup, or analysis. With repeated opportunities to test a hypothesis, the chance of at least one apparently unusual result can increase. Common approaches include prespecifying a primary endpoint, ordering hypotheses, or adjusting significance thresholds, but the record does not say whether any such procedure was used beyond identifying the primary endpoint. The posted secondary comparisons are unadjusted recalculations and should not be treated as a set of independent confirmatory tests.

Missing-data handling is also not reported in the registry record. This matters because an endpoint may be unavailable for participants who discontinue, miss diary entries, or otherwise lack an observation at the target timeframe. Different methods can make different assumptions about those missing values. The record does not explain whether the 7-day symptom average required a specified amount of diary completion, how incomplete weeks were handled, or how missing endpoint values were addressed. It is not appropriate to assume that every randomized participant contributed to each posted mean.

The primary population is identified as the ITT Analysis Set without nasal polyps. The registry record does not provide enough information to determine the exact analysis-set rules, or how participants with protocol deviations or incomplete treatment were handled. Nor does it report an adjusted primary model, sensitivity analyses, or the effect of alternative assumptions about missing observations. These omissions limit assessment of how robust the recalculated comparison is to analytic choices.

Although the trial is described as randomized and double masked, the randomization sequence, allocation concealment, and operational details of masking are not reported in the registry record. Interim analyses and stopping rules are also not reported in the registry record. Their absence from the registry entries should not be taken as evidence that such procedures were or were not used; it means the record does not document them.

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: rib fracture (3.0%), cellulitis (2.4%), migraine (2.4%), anxiety (2.4%), abortion spontaneous (2.4%).

The registry reports safety counts for the initial treatment period up to 24 weeks and for three extension groups. In the LYR-210 up to 24 Weeks group, 4 of 124 participants at risk had a serious adverse event reported; in the Sham Procedure Control up to 24 Weeks group, 4 of 66 participants at risk had a serious adverse event reported. The record lists 0 deaths in each of these groups. These are reported counts, not estimates of whether an event was caused by treatment.

For the extension groups, serious adverse events were reported for 2 of 42 at risk in LYR-210-LYR-210, 3 of 41 in LYR-210-Sham, and 3 of 48 in Sham-LYR-210. The record lists 0 deaths in each extension group. Because these groups represent extension treatment sequences, the counts should not be interpreted as a direct randomized comparison without further design and analysis details.

The serious-event terms listed most often include Rib Fracture (3.0%), Cellulitis (2.4%), Migraine (2.4%), Anxiety (2.4%), Abortion spontaneous (2.4%), and Nephrolithiasis (2.4%). These listings do not establish causality, and the registry record does not report enough detail to assess timing, severity, relatedness, or differences in exposure. Safety counts should be read alongside the group definitions and follow-up periods, not as proof for or against a treatment-related risk.

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

The primary summary describes average symptom-score change over 24 weeks among participants without nasal polyps. Both groups had negative mean changes, and the recalculated between-group estimate was -0.07. Its confidence interval crosses zero, and the unadjusted p-value is 0.847. Together, these statistics indicate that the posted unadjusted comparison does not precisely distinguish the groups' average changes.

This result does not show that the groups are equivalent, nor does it establish that the observed difference is clinically important or unimportant. An equivalence or noninferiority conclusion requires a prespecified margin and an analysis designed for that question; such a margin is not reported in the registry record. The record also does not report a threshold for meaningful change on the 3CS scale. Statistical uncertainty and clinical interpretation are related but distinct questions.

The results also do not describe every participant's experience. A group mean can mask a range of changes, and the posted summaries do not give responder counts or distributions of individual outcomes. The primary analysis concerns the specified ITT population without nasal polyps; it should not automatically be generalized to every adult with chronic rhinosinusitis, to people with nasal polyps, or to other populations not described in the record.

Secondary outcomes provide additional measures, but their unadjusted nature and the absence of a reported multiplicity procedure limit confirmatory interpretation. The adverse-event summaries describe reported events in the stated groups and periods; they do not establish that an event was caused by an intervention. Nor do the results establish outcomes beyond the reported timeframes. The registry record's missing analysis details, including missing-data handling and the original statistical plan, further limit what can be concluded from the posted summary statistics.

17. Why This Trial Matters Statistically

This trial illustrates why a clinical result should be read through both its estimate and its uncertainty. The primary mean changes are similar, and the recalculated difference is close to zero. The confidence interval crosses zero, so the point estimate alone should not be treated as a precise description of the underlying group contrast. The group standard deviations also show that participant outcomes vary around their means, an important context for interpreting an average.

The endpoint definition matters. The 3CS composite combines three daily symptom ratings on a bounded scale, and the primary analysis focuses on participants without nasal polyps. A reader should distinguish that targeted question from a broader question about all adults with chronic rhinosinusitis. The secondary outcomes address other dimensions of symptoms and imaging, but they use different scales and timeframes and are not substitutes for the primary endpoint.

The registry record also demonstrates the difference between a trial's own planned analysis and a recalculation from summary statistics. The latter is transparent about the simple group contrast but cannot recover details such as baseline adjustment, missing-data assumptions, or a prespecified multiplicity strategy. Those details are important for judging whether an estimate answers the trial's intended question and whether the result is robust to analytic choices.

Finally, planning illustrations based on the observed effect should not be confused with the trial's original design justification. Their very large figures for the primary comparison reflect the small observed mean difference used as the planning target; they are not observed power and do not reveal the assumptions used when the study was designed. Keeping these distinctions clear helps prevent overinterpretation of either an uncertain efficacy comparison or descriptive safety counts.

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 registry record contains limited detail about the statistical analysis. It does not report the sponsor's primary inferential analysis, the original sample-size justification, the planned analysis model, or the handling of missing data. The primary comparison discussed in the posted summaries is a recalculation from group means and standard deviations. It may not reflect adjustments or assumptions used in the trial's own analysis.

The primary endpoint is reported for the ITT Analysis Set without nasal polyps, with group counts of 101 and 54. The record does not explain the participant flow behind these analysis counts, how many diary records were needed to form the weekly average, or how incomplete measurements were treated. This limits assessment of selection and missing-data effects. The registry's enrollment figure is 196, but the record does not give a complete account of how enrollment relates to each endpoint analysis set.

The primary scale has a defined range and direction, but no clinically important difference is reported. This prevents a direct interpretation of whether an estimated score difference would matter to participants. The secondary comparisons are unadjusted recalculations, and multiplicity procedures are not reported. The result for the listed rescue-treatment outcome is also not reported in the registry record.

Safety results span the initial period and extension groups, whose treatment sequences differ. The registry summaries do not provide the detailed timing, exposure, seriousness criteria, or attribution needed to interpret individual event terms, and the extension groups are not presented as a direct randomized comparison. The record's description of crossover or continued treatment does not include enough detail to infer the structure or comparability of the extension data. These limitations call for a measured reading of the posted summaries, not assumptions about undocumented methods.

19. Related Tutorials

20. Related Statistical Calculators

21. Sources

• ClinicalTrials.gov: Efficacy and Safety of LYR-210 for the Treatment of Chronic Rhinosinusitis in Adults — NCT05219968.
• Registry record last updated 2025-05-02; status last verified 2025-04.
• Results first posted 2025-05-02.
• 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

NCT05219968 is the completed phase III ENLIGHTEN 1 randomized, double-blind, parallel-group trial of LYR-210 for adults with chronic rhinosinusitis. The registry lists enrollment of 196 and describes a multicenter study with a safety extension involving crossover or continued treatment.

The primary endpoint is change from baseline in the 7-day average 3CS score at 24 weeks among participants without nasal polyps. The unadjusted recalculated mean difference is -0.07, with a 95% confidence interval that includes zero and an unadjusted p-value of 0.847. Secondary summaries cover all-participant 3CS, SNOT-22, and CT score changes; a result for the listed rescue-treatment outcome is not reported in the registry record. Serious adverse-event counts are reported for the initial and extension groups. The original statistical plan, missing-data methods, and multiplicity procedures are not reported in the registry record.