Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis (NCT05990725), a na phase 3 study. The primary outcome is Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) Total Score Less Than or Equal to (<=) 7 at Week 24.

2. Clinical Question

3. Trial Design

This is a Phase 3b, open-label study of lebrikizumab for adults and adolescents with moderate-to-severe atopic dermatitis. Its design is recorded as single-group; allocation is not applicable and masking is listed as none. The registry record lists enrollment of 260. The study status is completed, with a start date of 2023-11-20 and primary completion date of 2025-06-25.

Participants received lebrikizumab. The registry description specifies 500 mg subcutaneous loading doses at Day 1 and Week 2, then 250 mg every two weeks from Week 4 to Week 16. It states that frequency is reduced to every 4 weeks at Week 16, but the remaining schedule is cut off in the record. The brief summary identifies 24 weeks of treatment as the period for evaluating improvement in disease severity, signs, and symptoms.

Because the study has no listed concurrent comparator, its central efficacy question is about response observed during treatment, not a difference between treatment groups. Open-label conduct also means participants and investigators were not masked to treatment, according to the record. The EASI outcome is assessed by an investigator or trained designee, so awareness of treatment is relevant context when interpreting an assessment-based endpoint.

The primary endpoint is the percentage achieving an EASI total score of 7 or lower at Week 24. The population description identifies a modified analysis set that excludes participants from one study site from the full analysis set. The registry record does not give the number excluded, define the full analysis set, or report how missing Week 24 assessments were handled. It also does not report a statistical analysis plan or a numerical primary-endpoint estimate.

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 260 participants were enrolled in this study.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The modified analysis set (mFAS) included all participants from the FAS, excluding those enrolled in one study site.

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: Full Analysis Set (FAS) included all enrolled participants.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved Eczema Area and Severity Index (EASI) Total Score Less Than or Equal to (<=) 7 at Week 24, measured over At Week 24.

The primary endpoint is the percentage of participants with an EASI total score of 7 or lower at Week 24. EASI is a composite assessment of the severity and extent of atopic dermatitis. Investigators or trained designees assess erythema, induration or papulation, excoriation, and lichenification across the head and neck, trunk, upper limbs, and lower limbs. They also assess the extent of affected skin in those body areas. The total score ranges from 0 to 72, with higher scores representing more severe and extensive disease.

A threshold endpoint translates a continuous score into a responder category: participants either meet the stated threshold or do not. Reporting the percentage meeting it can make the result more interpretable as a description of how often a defined level of disease severity was reached. It also loses information about the exact scores and how far participants are from the threshold. A score just above the cutoff and a much higher score both fall outside the responder category, despite potentially representing different clinical states.

The record specifies a 95% confidence interval for this percentage, which would describe the uncertainty around the estimated response proportion. However, the Week 24 percentage and its interval are not reported in the registry record. The endpoint definition alone therefore does not establish the observed response.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study design determines which statistical questions can be answered. This record describes an open-label, single-group study, with allocation listed as not applicable and masking as none. In a randomized comparison, treatment groups can be compared directly under the randomization scheme. In a single-group study, there is no concurrent randomized group to serve as that reference. The main efficacy result, if reported, would be a description of outcomes among participants receiving the study treatment, rather than an estimate of a treatment contrast.

What does a responder percentage describe?

The primary outcome is binary at the participant level: a participant either achieves an EASI total score of 7 or lower at Week 24 or does not. The response percentage is the number of participants meeting that definition expressed relative to the analysis population used for the calculation. It is not the average EASI score, and it does not convey the full distribution of scores. Thresholds are useful for communicating whether participants reached a prespecified state, but categorizing scores discards information about the distance from the threshold and changes that do not cross it.

The endpoint definition describes EASI as an assessment of both disease severity and extent. Severity ratings cover erythema, induration or papulation, excoriation, and lichenification in four body areas, while extent is assessed as the percentage of each area affected. The resulting total ranges from 0 to 72; higher values indicate more severe and extensive disease. Because the assessment depends on investigator ratings, consistent training and application of scoring procedures matter. The registry record identifies an investigator or trained designee as assessor, but does not describe quality-control procedures.

How should the confidence interval be read?

A confidence interval expresses statistical uncertainty around an estimated quantity. For a response percentage, it gives a range of values compatible with the observed data under the interval method and its assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The interval does not remove limitations in the study design, correct bias, or guarantee that a treatment effect is causal. The record specifies a 95% confidence interval for the primary endpoint, but does not report the estimate or its interval.

Precision depends in part on the analysis denominator and the number of observed responses. Exclusions and missing outcome measurements can alter both. The population is described as a modified full analysis set that excludes participants from one study site. The registry record does not report how many participants were excluded, the number assessed at Week 24, or the approach to missing data. Without those details and the outcome estimate, the precision of the primary endpoint cannot be evaluated.

Why does the single-group design matter?

An observed response proportion answers a descriptive question about the study group. It does not provide the counterfactual outcome that the same participants might have experienced without lebrikizumab or under an alternative treatment. A before-and-after comparison, if one were reported, would still be vulnerable to changes over time unrelated to treatment and to measurement effects. No baseline-to-follow-up analysis result is included in the registry record described by the record.

Open-label conduct is also relevant. Participants and investigators knowing which treatment is given may affect reporting, adherence, co-interventions, or assessment. This does not establish that bias occurred, but it identifies a source of possible influence that differs from a masked design. The record does not report procedures intended to reduce such influence.

What do planning illustrations mean?

Sample-size calculations can illustrate the amount of information that might be needed to detect a specified effect under stated assumptions. The planning assumptions associated with this study describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of an observed effect. These assumptions describe planning illustrations, not the trial’s own design: the actual study is single-group, not a two-arm randomized comparison. Any sample-size figure generated under those assumptions would be hypothetical and should not be interpreted as observed power or as evidence that the study was designed around that calculation.

The record does not report a statistical analysis plan, sample-size justification, interim analysis approach, or the specific effect used for a planning illustration. No new treatment contrast can be inferred from the planning assumptions. Sample-size planning relates to a hypothetical future comparison under specified conditions; it does not change the interpretation of the observed outcomes in this single-group study.

What is not available for statistical assessment?

The registry record lists 14 outcome measures and zero analysis records. It defines the primary endpoint but does not report its Week 24 estimate or confidence interval. It also does not report multiplicity procedures, detailed model specifications, missing-data methods, or a sensitivity analysis. These omissions limit assessment of how the endpoint was estimated and how robust the result would be to alternative analytic choices. No unreported procedure should be assumed.

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("Lebrikizumab")
n      <- c(247)
events <- c(185)
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  Lebrikizumab  247  185  74.9  69.0  80.2  69.1  79.9  69.1  79.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures, including the primary EASI threshold and secondary outcomes involving additional EASI cutoffs, EASI 75 and EASI 90, investigator global assessment, SCORAD, hand lesion symptoms, itch, and dermatology-related quality of life. When a study examines multiple outcomes or repeated visits, the chance of at least one apparently favorable finding can increase if each result is interpreted without accounting for the broader set of tests. Statistical methods may address this through a prespecified testing sequence or other multiplicity procedure. Such a procedure is not reported in the registry record, so it is not possible to determine whether secondary analyses were adjusted or how their results were intended to support conclusions.

The primary endpoint population is described as the modified analysis set, comprising participants in the full analysis set except those enrolled at one study site. The record does not define the full analysis set, state the reason for the site exclusion, or give the number of participants in the resulting analysis population. It also does not describe missing-data handling, treatment of participants who discontinue, or sensitivity analyses. These choices matter because they can affect the response denominator and the interpretation of a Week 24 percentage.

Zero analysis records are listed, and no numerical primary result is reported in the registry record. Consequently, the data cannot be checked for alignment between the stated analysis population and the endpoint denominator, nor can the effect of missingness or multiplicity procedures be assessed. These points are unavailable details, not evidence that a particular method was or was not used outside the registry record.

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: dermatitis atopic (0.4%), erythrodermic atopic dermatitis (0.4%), mitral valve prolapse (0.4%), anal fistula (0.4%), chest discomfort (0.4%).

For the lebrikizumab group, the registry record lists 260 participants at risk for serious adverse events and 7 with serious adverse events. It also lists 260 at risk for other adverse events and 127 with other adverse events. Deaths are recorded as 0. These counts describe events in the study group; because there is no concurrent comparator, they do not estimate a difference in safety between treatments.

The serious-event terms listed include dermatitis atopic, erythrodermic atopic dermatitis, mitral valve prolapse, anal fistula, chest discomfort, and herpes simplex. Each term is shown with a percentage of 0.4%. These term-level entries should be read as registry-reported descriptions, not as evidence about causation or comparative risk. The record does not provide enough detail to infer whether participants could contribute more than one event or how event terms were coded.

Serious adverse events and other adverse events are separate registry categories. The counts should not be added or treated as mutually exclusive participant groups. They are descriptive observations over the study period, and the registry information does not give exposure-adjusted rates, event timing, or a control-group comparison.

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

The registry record defines a clinically interpretable primary outcome: whether participants reached an EASI total score of 7 or lower at Week 24. It also describes how EASI combines investigator assessments of disease signs and affected skin extent. This makes clear what the planned response measure represents and when it is assessed.

However, the registry record does not report the primary response percentage or its 95% confidence interval. The registry entries therefore do not establish how many participants met the endpoint, the size of the response estimate, or its statistical precision. A study marked completed is not, by itself, a numerical efficacy result. The endpoint definition and the treatment schedule cannot substitute for observed outcome data.

Even if a response estimate were reported, its meaning would be limited by the single-group, open-label design. It would describe outcomes among participants treated in this study, not the difference attributable to lebrikizumab relative to a concurrent control. Without a comparator, changes cannot be separated from other influences with the same confidence as in a randomized controlled comparison. Open-label assessment also warrants awareness that expectations or knowledge of treatment could influence reporting or investigator ratings, although the record does not establish that such influence occurred.

The modified analysis set excludes participants from one study site, but the record does not explain the reason, give the resulting denominator, or describe how missing assessments were handled. Those details are important to judging who the reported percentage would represent. The secondary outcomes broaden the range of disease and quality-of-life measures named in the record, but their results are not reported in the registry record for this analysis.

The safety counts provide descriptive information about adverse events in the lebrikizumab group. They do not establish comparative safety, and the serious-event terms do not show that treatment caused those events. Overall, the record supports understanding the study question and design, but not estimating the primary efficacy response or making a comparative treatment claim.

14. Why This Trial Matters Statistically

This study raises a useful statistical distinction between defining an outcome and reporting its result. The registry record describes a threshold-based EASI endpoint at Week 24 and specifies a confidence interval, but the numerical estimate and interval are not reported. A clearly defined endpoint helps readers understand what investigators intended to measure; without the result, it cannot show the observed frequency of response or its precision.

The single-group, open-label design also makes the target of inference important. A response proportion in a treated cohort can describe the experience of those participants, but it is not a treatment-effect contrast. Statistical interpretation should match the design rather than treating an uncontrolled response as if it came from a randomized comparison. This distinction is particularly important when an endpoint is assessed by investigators and the study is unmasked.

The analysis population provides another important interpretive issue. The primary endpoint applies to a modified analysis set that excludes participants at one study site. Since the record does not state the resulting denominator, reason for exclusion, or handling of missing Week 24 assessments, readers cannot assess how those decisions shape the reported population or precision. These are not minor presentation details: denominator definitions are part of what a response percentage means.

Finally, the registry lists a range of secondary outcomes and no analysis records. In a study with multiple endpoints and visits, transparent reporting of the analysis plan and multiplicity approach helps distinguish primary evidence from exploratory findings. The record does not report those methods. Together, these points illustrate why statistical appraisal depends on design, estimand, analysis population, missing-data handling, uncertainty, and complete outcome reporting—not just the name of an endpoint.

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.

The principal limitation for interpreting efficacy is that the registry record does not report the primary Week 24 response percentage or its 95% confidence interval. Although the study status is completed and the endpoint is defined, the magnitude and precision of the observed result cannot be evaluated from the reported details. The record lists zero analysis records.

The study is single-group and open-label, with no concurrent comparator listed. It can describe outcomes among participants receiving lebrikizumab, but cannot by itself distinguish treatment-associated change from changes that might occur for other reasons. The open-label design also leaves potential for expectations or knowledge of treatment to influence participant reporting or investigator assessment; the record does not establish whether this occurred.

The primary analysis population is modified: participants from one study site are excluded from the full analysis set. The rationale and number excluded are not reported in the registry record. The record also does not define the full analysis set or explain missing outcome handling, discontinuation rules, or sensitivity analyses. As a result, the intended denominator and the effect of missing assessments on the endpoint are unclear.

Although 14 outcome measures are listed, multiplicity procedures and a detailed statistical analysis plan are not reported. The truncated dosing description also does not give the full schedule after the stated transition to every 4 weeks at Week 16. These gaps constrain interpretation of the analysis and treatment exposure without establishing that any particular procedure was absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Effectiveness and Safety of Lebrikizumab Treatment in Adults and Adolescents With Moderate-to-Severe Atopic Dermatitis — NCT05990725.
• Registry record last updated 2026-07-17; status last verified 2026-05.
• Results first posted 2026-07-17.
• 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

NCT05990725 is a completed Phase 3b, open-label, single-group study of lebrikizumab in adults and adolescents with moderate-to-severe atopic dermatitis. The registry lists enrollment of 260, a study start date of 2023-11-20, and a primary completion date of 2025-06-25. The primary endpoint is the percentage achieving an EASI total score of 7 or lower at Week 24, assessed in a modified analysis set that excludes participants enrolled at one study site.

The registry record describes the endpoint and specifies a 95% confidence interval, but does not report the Week 24 estimate or interval. It lists 14 outcome measures and zero analysis records. Safety entries include 7 participants with serious adverse events, 127 with other adverse events, and 0 deaths in the lebrikizumab group. With no concurrent comparator, the study’s results are descriptive rather than a randomized treatment comparison.