Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52) (NCT05049122), a na phase 4 study. The primary outcome is Percentage of Participants With NPS Improvement From Baseline >=1 at Week 24.

2. Clinical Question

The primary question is about the proportion meeting a prespecified threshold for improvement, rather than the average change in score. The registry record describes the Nasal Polyp Score as a combined assessment of the right and left nostrils, based on central review of video recordings of nasal endoscopy. The score ranges from 0 to 8, with higher values indicating greater severity.

Because the study has no control group, the endpoint describes the observed response in this treated group. It cannot by itself establish how participants would have fared over the same period without dupilumab or under a different treatment. The registry record does not report the percentage meeting the endpoint, its confidence interval, or the number of participants included in that endpoint analysis. The central result therefore cannot be evaluated from the posted results.

3. Trial Design

This was a Phase 4, open-label, single-arm, multicenter study in Japanese adults with chronic rhinosinusitis with nasal polyps that was not adequately controlled with existing therapies. The listed enrollment was 25. The study is recorded as completed, with a start date of 2021-10-22 and a primary completion date of 2022-12-21. Sanofi is listed as the sponsor.

All participants were assigned to the dupilumab group; the record describes subcutaneous dupilumab monotherapy. Dosing was every 2 weeks, with the interval potentially changed to every 4 weeks at Week 24. The study was open-label, meaning treatment masking was not used. The registry record does not report a separate comparator group or a randomized allocation process.

Per-participant follow-up included a screening period of 2 to 4 weeks and an intervention period of up to 52 weeks ±3 days. The primary endpoint was assessed at Week 24. Other listed outcomes at Week 24 included changes in bilateral Nasal Polyp Score, nasal congestion or obstruction symptom severity, sinus opacification on computed tomography using the Lund Mackay score, total symptom score, loss-of-smell symptom severity, and a rhinosinusitis visual analogue scale. The record also lists treatment-emergent adverse events, serious adverse events, and events leading to treatment discontinuation during the 24-week treatment period.

The design can describe outcomes and safety events observed among participants receiving dupilumab in this study. It does not provide a concurrent control for separating treatment-associated changes from changes that might occur over time, effects of expectations or assessment, or other influences. The registry record does not report a protocol rationale for the selected design, a sample-size justification, or details about how the planned enrollment was determined.

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: The study consisted of a screening period (up to 4 weeks) and a treatment period (up to 52 weeks). A total of 25 participants were enrolled in this study. The study duration for each participant was up to 56 weeks.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Per protocol (PP) analysis set consisted of all participants in modified intent-to-treat (mITT) set (Enrolled population with chronic rhinosinusitis with nasal polyp \[CRSwNP\] allocated to study treatment administered at least 1 dose of study treatment) and who did not receive intranasal corticosteroids (INCS) up to Week 24

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 Enrolled analysis set consisted of all participants with a treatment kit number allocated and recorded in the interactive response technology (IRT) database, regardless of whether the treatment kit was used or not.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With NPS Improvement From Baseline >=1 at Week 24, measured over Baseline (Day 1) and Week 24.

The primary endpoint is the percentage of participants whose bilateral Nasal Polyp Score improved from baseline by at least 1 point at Week 24. The score combines assessments of the right and left nostrils, using central video recordings of nasal endoscopy. Each nostril receives a grade based on polyp size, and the combined score ranges from 0 to 8; higher scores indicate greater severity. Baseline is defined in the registry record as the last available value before the first study treatment administration.

This endpoint turns a change in a severity score into a responder classification: each participant either meets the stated improvement threshold or does not. Reporting the percentage meeting that threshold can make the result easier to interpret than a score change alone, but it also leaves out how far individual participants changed beyond the threshold. A participant just meeting the threshold and one with a larger improvement both count as responders for this endpoint.

The registry record identifies a 95% confidence interval as the measure of dispersion for the primary endpoint. In general, a confidence interval conveys uncertainty around an estimated proportion; a wider interval indicates less precision than a narrower one. The record does not report the actual endpoint estimate or interval, so neither the observed response proportion nor its precision can be assessed. The endpoint is also a within-group measure: without a comparator, it does not estimate the difference in response that would be attributable to dupilumab relative to another treatment or no treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a binary responder endpoint: participants are classified according to whether their bilateral Nasal Polyp Score improved from baseline by at least 1 point at Week 24. The endpoint is summarized as a percentage, with a 95% confidence interval specified as the measure of uncertainty. The estimate and interval themselves are not reported in the registry record.

What a responder percentage represents

A responder percentage is the share of analyzed participants who meet the stated criterion. It differs from a mean change because it focuses on the proportion crossing a threshold, not the average size of change across the group. This can be useful when a threshold defines a meaningful category for the study question. However, categorization discards some information: it does not distinguish participants who narrowly meet the threshold from those with larger score changes, and it treats participants just below the threshold as nonresponders.

For this endpoint, the starting measurement is the last available value before the first study treatment administration. The score is derived from nasal endoscopy video assessments of both nostrils. The record explains that nostril grades depend on polyp size and that the combined score ranges from 0 to 8, with higher scores indicating greater severity. These details define what the endpoint is intended to capture, but they do not supply the observed distribution of scores or changes.

How to read a confidence interval

In general, a confidence interval expresses uncertainty around an estimated quantity. For a responder proportion, it gives a range of values compatible with the data and the method used to construct the interval. A point estimate alone can appear more definitive than the data warrant; the interval helps show how much precision the study achieved. The actual interval is not reported in the registry record, so its width and the precision of the estimate cannot be evaluated.

Precision depends in part on how many participants contribute to an analysis and on the observed response pattern. The listed enrollment is 25, but the primary analysis population and its count are not reported. A confidence interval calculated from the analyzed participants would reflect that analysis denominator, not automatically the full enrollment. The incomplete description of the per-protocol set makes it especially important not to assume that all enrolled participants contributed to the primary endpoint.

What a single-group design can estimate

In general, a single-group study can describe outcomes observed among participants who received the study treatment. A baseline-to-follow-up endpoint can characterize change or response in that group. Without a comparison group, however, the study cannot estimate a treatment-versus-control contrast. The observed proportion cannot alone distinguish treatment effects from natural change, other care, measurement variation, or influences associated with study participation. These are design limitations, not defects that can be resolved by a more precise confidence interval.

The open-label design means that participants and study staff were not masked to treatment. The record does state that Nasal Polyp Score was assessed from central video recordings, but it does not report the complete procedures for review or how the assessors' awareness was handled. Central review is part of the endpoint description; no further assumptions about its conduct are warranted.

Analysis populations and missing information

The registry record describes the per-protocol population as participants in a modified intent-to-treat set who also met additional conditions. The description ends after a reference to intranasal corticosteroid use, so the full criteria are not reported in the registry record. The number analyzed, handling of missing Week 24 assessments, and rules for deriving responder status when a measurement is unavailable are also not reported in the registry record. Without these details, the analysis denominator and potential effects of missingness cannot be assessed.

The registry record lists no analyses in its analysis count. It does not report a detailed statistical analysis plan, the method used to calculate the confidence interval, or adjustments for multiple outcomes. A stated confidence-interval type identifies the intended form of uncertainty summary, but not every implementation detail. No specific inferential procedure should be attributed to the study without a reported method.

Planning illustrations are not trial results

Any accompanying sample-size calculations are planning illustrations, not results from this study. The described illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect set as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustration reports participants per arm. These assumptions describe a hypothetical planning exercise and do not turn this single-arm study into a two-arm comparison. They are not the trial's own sample-size justification and are not observed power. The registry record does not report a sample-size justification for the study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("Dupilumab 300 mg")
n      <- c(25)
events <- c(23)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  Dupilumab 300 mg  25  23  92.0  74.0  99.0  75.0  97.8  74.9  97.6

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and several secondary outcomes. These include nasal polyp score, symptom measures, a sinus imaging score, and adverse-event outcomes. When a study assesses multiple outcomes, the chance of at least one apparently notable result can increase if many tests are performed without a planned strategy for interpreting them. In general, multiplicity methods can control or organize this issue, but the registry record does not report a multiplicity adjustment or a hierarchy for interpreting the outcomes.

The record specifies a 95% confidence interval for the primary endpoint, but does not report the interval or the method used to calculate it. It does not report whether secondary outcomes were treated as exploratory or whether their analyses were adjusted for multiple comparisons. No analyses are listed in the registry analysis count. The absence of a reported multiplicity method means readers should not assume that the outcomes were adjusted or that each one provides an independent confirmatory test.

Missing-data procedures are not reported in the registry record. The record does not say how missing Week 24 endoscopy assessments or other outcome measurements were handled, whether participants with incomplete follow-up were included in particular analyses, or what assumptions were used for missing values. The primary population description is incomplete: it identifies a per-protocol set derived from a modified intent-to-treat set and additional conditions, but cuts off before the full criteria. The analyzed population size is not reported. These omissions limit assessment of who contributed to the results and whether missing observations could affect their interpretation.

12. 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: suicide attempt (4.0%), vestibular neuronitis (4.0%).

The safety figures list 25 participants at risk in the dupilumab group. The record reports 2 participants with serious adverse events, 10 with other adverse events, and 0 deaths. These are counts observed in the study; they are not comparisons with another group. The record also lists Suicide Attempt and Vestibular neuronitis among the top serious adverse-event terms, each reported as 4.0%.

Counts and percentages answer different questions: counts state how many participants were recorded, while a percentage expresses the proportion relative to a denominator. The listed serious-event terms should be read as event-category information, not as a complete account of each participant's clinical course. The record does not report enough detail to determine whether categories overlap at the participant level, how long participants were followed for each safety outcome, or the full event narratives. Nor does the presence of an event term establish that the study treatment caused the event.

These figures describe safety observations among participants in an open-label, single-arm study. Without a control group, they cannot estimate how event rates compare with another treatment or with no study treatment. The registry record's safety counts should therefore be read descriptively, alongside the limits of the study design and the details available in the posted results.

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

The study addresses a defined question: the percentage of Japanese adults with inadequately controlled chronic rhinosinusitis with nasal polyps who had at least a 1-point improvement in bilateral Nasal Polyp Score at Week 24 while receiving dupilumab. The record describes the endpoint, the treatment schedule, and a completed, open-label, single-arm design. It also lists other efficacy and safety outcomes.

What the record does not establish is the primary observed response. The percentage meeting the endpoint, the confidence interval, and the analysis denominator are not reported in the registry record. Without those items, readers cannot judge the response magnitude or its precision. The outcome listings alone are not results, and the study's completion status does not fill in missing result values.

Even if an observed response estimate were available, a single-arm study would describe the outcome within the treated group rather than provide a controlled estimate of the difference attributable to treatment. Changes from baseline may be informative as descriptions of participants' courses, but there is no concurrent comparison group to help separate treatment-associated change from other influences. The open-label design is also relevant when considering subjective symptom measures and assessment procedures.

The safety counts report events recorded among participants, including serious adverse events and deaths. They do not establish causation and cannot be compared with an unobserved control group. The figures are useful as descriptive information in the registry record, but they do not alone characterize the full balance of risks and benefits.

Accordingly, this record supports understanding of the question studied and the limits of its design, but not a conclusion about the primary endpoint result. It does not support medical advice or a treatment recommendation. Interpretation of efficacy and safety would require the missing outcome estimates, analysis details, and context not reported in the registry record.

14. Why This Trial Matters Statistically

This study is a useful example of why endpoint definitions and study design need to be considered together. The primary outcome is a responder proportion based on a defined change in a bilateral endoscopic score. The definition makes clear what counts as a response, while the specified confidence interval indicates that uncertainty around the proportion was intended to be summarized.

At the same time, the single-arm design sets a boundary on inference. A response proportion can describe the study group, but it cannot provide a controlled treatment contrast. The open-label structure and lack of a comparator are important context even before considering the size or precision of any result. Statistical precision and causal interpretation are different issues: a narrow interval would not remove the limitations created by the absence of a control group.

The registry record also illustrates the importance of transparent reporting. It identifies enrollment and a per-protocol analysis population but does not report the primary endpoint estimate, its interval, or the number analyzed. The analysis-population description is incomplete, and missing-data and multiplicity procedures are not reported in the registry record. These gaps make it difficult to assess the result even though the endpoint itself is clearly described.

Finally, planning calculations should not be confused with trial findings. The accompanying planning illustrations use hypothetical assumptions and do not represent observed power or a justification for the enrollment in this study. Keeping design, estimation, and planning distinct helps readers avoid treating an illustrative calculation as evidence about the study's outcome.

15. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to this record. It describes an open-label, single-arm study with no control group, so it cannot provide a direct comparison with placebo, usual care, or another treatment. The registry record does not report random allocation or masking. These design features limit the ability to attribute observed changes solely to the study treatment.

The primary endpoint result is not reported in the registry record. The record also omits the endpoint confidence interval and the number of participants included in the primary analysis. Although enrollment is listed as 25, that figure should not be assumed to be the denominator for the primary endpoint. The per-protocol population description is incomplete, preventing a full assessment of eligibility and analysis-set rules.

Missing-data handling, the statistical method for the confidence interval, and multiplicity procedures are not reported in the registry record. The record lists several secondary outcomes but does not provide their results. It also does not report a sample-size justification or detailed statistical analysis plan. These omissions restrict assessment of precision, analysis choices, and the interpretation of multiple outcomes.

The safety information is descriptive and comes from the study group without a comparator. The listed counts do not establish causality, and the available record does not provide full event narratives or all details needed to interpret event timing and participant-level overlap. These limitations apply to interpretation of this registry record and do not imply conclusions beyond what it reports.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Dupilumab in Japanese Patients With Chronic Rhinosinusitis With Nasal Polyp (SINUS-M52) — NCT05049122.
• Registry record last updated 2025-09-11; status last verified 2025-09.
• Results first posted 2024-01-22.
• 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.

19. Record Summary

NCT05049122 is a completed Phase 4, open-label, single-arm, multicenter study of subcutaneous dupilumab monotherapy in Japanese adults with chronic rhinosinusitis with nasal polyps not adequately controlled with existing therapies. Listed enrollment was 25. The study started on 2021-10-22, and primary completion was recorded on 2022-12-21.

The primary endpoint was the percentage of participants with at least a 1-point improvement in bilateral Nasal Polyp Score from baseline to Week 24. The registry record does not report the primary estimate, its 95% confidence interval, or the number analyzed. It lists additional Week 24 efficacy outcomes and reports safety counts, including 2 participants with serious adverse events and 0 deaths. The single-group design supports descriptive interpretation but does not provide a controlled comparison.