Study to Assess the Safety and Efficacy of Lebrikizumab (LY3650150) in Adolescent Participants With Moderate-to-Severe Atopic Dermatitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Assess the Safety and Efficacy of Lebrikizumab (LY3650150) in Adolescent Participants With Moderate-to-Severe Atopic Dermatitis (NCT04250350), a na phase 3 study. The primary outcome is Percentage of Participants Discontinued From Study Treatment Due to Adverse Events (AEs).

2. Clinical Question

The clinical question is therefore descriptive: among the adolescents enrolled in this study, how often did adverse events lead to discontinuation of study treatment during the planned treatment period? The primary endpoint concerns treatment discontinuation attributed to adverse events; it is not a count of all adverse events, all serious adverse events, or all participants who experienced any adverse event.

The record also lists secondary outcomes covering investigator assessment, eczema severity, body surface area, and patient-reported anxiety and depression. These outcomes address different aspects of disease status and participant experience. Their inclusion does not establish that results were analyzed or reported. The record lists 12 outcome measures overall, while the analysis count is 0.

Because there is no comparator, the study cannot estimate a treatment contrast against an untreated or differently treated group. The observed counts can describe what was recorded among participants in this study, but they cannot by themselves distinguish treatment effects from other explanations. No primary-endpoint percentage, uncertainty interval, or efficacy result is reported in the registry record.

3. Trial Design

The registry identifies this as a Phase 3, open-label, single-group study of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. Enrollment was 206. The study was completed, and its stated duration was 52 weeks. The record gives a start date of 2020-02-11 and a primary completion date of 2022-04-20.

All participants received lebrikizumab according to the regimen described in the record: two subcutaneous injections of 250 mg at baseline and Week 2, then a single injection every 2 weeks from Week 4 until before Week 52. There was no random allocation and no masking. The registry's allocation entry is NA, consistent with the described single-group design. No independent control arm is listed.

Open-label means participants and study personnel were not masked to the assigned treatment. In a single-group study, the absence of a comparator also means there is no concurrent group to provide a direct reference for outcome rates. These features matter when interpreting both subjective assessments and adverse-event reporting: observations describe the study participants under the study conditions, rather than a randomized comparison.

The primary endpoint was the percentage of participants who discontinued study treatment due to one or more adverse events, assessed cumulatively at Week 52. The primary endpoint population is described as all enrolled participants. The record separately lists secondary outcomes, including Investigator Global Assessment response, EASI response and change, body surface area change, and PROMIS anxiety and depression change. It does not report the results or analysis methods for those outcomes.

The registry record does not report the rationale for the enrollment target, a sample-size justification, interim analyses, or a detailed statistical analysis plan. Those design details should not be inferred from the completed status or from the enrollment count.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All enrolled participants.

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: All enrolled or randomized participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Discontinued From Study Treatment Due to Adverse Events (AEs), measured over Week 52.

The primary endpoint is the percentage of participants who discontinued study treatment because of one or more adverse events, summarized cumulatively through Week 52. Its population is described as all enrolled participants. The endpoint focuses on a specific consequence of adverse events: stopping study treatment. It is not equivalent to the percentage with any adverse event, the percentage with a serious adverse event, or the number of individual event reports.

As a general statistical concept, a percentage expresses the number of participants meeting a defined condition relative to an eligible population. For an endpoint such as treatment discontinuation, the condition and analysis period need to be clear: a participant is counted if discontinuation was attributed to one or more adverse events during the specified period. A cumulative measure reflects whether the event occurred by the end of that period, rather than how many times it occurred.

This type of endpoint can describe how often adverse events were associated with stopping treatment in the study. It does not, by itself, establish that treatment caused an event or that a particular rate would occur in another population. Attribution, follow-up, and the study's open-label single-group design all shape interpretation.

The registry record names the endpoint and its timeframe but does not report the endpoint result, its numerator, or an uncertainty interval. The serious and other adverse-event counts listed separately cannot be substituted for the discontinuation result: they describe different outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group study rather than a randomized comparison. That design determines what the data can estimate. A study can report the proportion of its participants meeting an endpoint, but without a comparator it cannot directly estimate a difference attributable to lebrikizumab relative to another treatment. The reported enrollment was 206, and the record identifies all enrolled participants as the primary endpoint population.

What does a percentage endpoint represent?

As a general statistical concept, a participant-level percentage summarizes how many people meet a specified definition over a specified period. For this study's primary endpoint, that definition is discontinuation from study treatment due to one or more adverse events, assessed cumulatively through Week 52. A participant-level endpoint differs from an event count: one person may have more than one adverse event, while the endpoint concerns whether treatment discontinuation occurred because of at least one such event.

To interpret a percentage fully, readers need the numerator, denominator, rules for handling incomplete follow-up, and the method used to assign events to the endpoint. The registry record identifies the intended population and timeframe, but does not report the primary-endpoint numerator or percentage. It also does not describe how missing observations were handled. Thus, the endpoint's definition is available, but its estimate and precision are not reported in the registry record.

What does an uncertainty interval add?

As a general explanation, a confidence interval describes the statistical uncertainty around an estimated quantity under a specified method. It is not a guarantee that the true value lies within the interval, and it does not address every source of bias. For a single-group percentage, an interval can indicate how imprecisely the observed rate estimates a broader underlying rate under the model's assumptions. No confidence interval for the primary endpoint is reported in the registry record.

Precision and design validity are separate issues. A narrow interval would not remove concerns about the absence of a comparator, open-label assessment, or incomplete follow-up. Conversely, the lack of a reported interval does not mean the underlying estimate has no uncertainty; it means its precision cannot be assessed from the registry results.

Why does the single-group design matter?

In a randomized comparison, treatment groups can be compared under a design intended to balance measured and unmeasured factors on average. This study has no randomized control group. Any observed rate would therefore be descriptive of participants who received lebrikizumab in this study. It would not, by itself, establish what would have happened to the same participants under a different treatment or without study treatment.

The open-label design means treatment assignment was known. General statistical reasoning recognizes that knowledge of treatment can influence reporting, follow-up, decisions to discontinue, and subjective assessments. This does not show that any particular result was biased; it identifies a possible limitation when interpreting uncontrolled, unmasked observations.

How should the safety counts be understood?

The adverse-event summary distinguishes participants at risk from participants affected, and distinguishes serious from other adverse events. These categories should not be conflated with the primary endpoint. A serious adverse event is not necessarily a reason for treatment discontinuation, and a discontinuation due to an adverse event need not be a serious adverse event. The record's serious-event description also states that events are summarized regardless of causality.

For the lebrikizumab group, the record reports 5 affected among 206 at risk for serious adverse events, and 133 affected among 206 at risk for other adverse events. It separately lists 1 death. These figures are reported counts. They do not provide a comparative risk estimate, and no causal attribution should be inferred from their presence in a treatment study.

What do planning calculations mean?

As a general concept, sample-size calculations estimate how much information a future study may need under specified assumptions. The planning assumptions associated with the posted calculations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect stated as a fraction of the observed effect. For non-time-to-event outcomes, such planning values refer to participants per arm; time-to-event calculations are described in terms of total events.

These are planning illustrations, not observed power and not evidence that this trial was designed as a two-arm study. This trial is single-group, and its registry record does not report a sample-size justification. The assumptions do not supply a treatment contrast for the actual study. Sample-size outputs cannot replace observed endpoint results, nor can they establish that an effect was detected.

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 250 mg")
n      <- c(206)
events <- c(5)
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 250 mg  206  5  2.4  0.8  5.6  1.0  5.6  1.1  5.5

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 12 outcome measures, including the primary discontinuation endpoint and secondary disease-severity and patient-reported outcomes. It reports 0 analyses. The presence of several outcomes raises general questions about multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the number and relationship of tests. The registry record does not report a multiplicity procedure, such as a prespecified testing sequence or adjustment method.

There are no reported analysis results from which to assess whether outcomes were tested, which estimates were emphasized, or how any testing strategy was implemented. No p-values, effect estimates, confidence intervals, or outcome-specific results are reported in the registry record. The number of listed measures alone does not show that all were analyzed or that any particular multiplicity adjustment was used.

Missing-data handling is also not reported in the registry record. This matters because incomplete follow-up can affect the denominator and the interpretation of a cumulative percentage. The record identifies all enrolled participants as the primary endpoint population, but does not state how participants with missing endpoint status were treated, whether any imputation was used, or how withdrawals were incorporated.

The record does not describe an analysis population for secondary outcomes or a detailed statistical analysis plan. No assumptions about interim analyses, missing-data methods, or adjusted analyses should be inferred. These omissions limit assessment of how the planned outcomes would have been analyzed and how robust any estimate might be to incomplete data.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: testicular torsion (1.0%), cardiac arrest (0.5%), bile duct stone (0.5%), multiple injuries (0.5%), dermatitis atopic (0.5%).

The registry's safety summary reports 5 participants affected among 206 at risk for serious adverse events, and 133 affected among 206 at risk for other adverse events. It separately lists 1 death. These counts describe different safety categories and should not be combined or substituted for the primary endpoint, which concerns discontinuation from study treatment due to adverse events.

The serious-event terms listed with percentages are Testicular torsion, 1.0%; Cardiac arrest, 0.5%; Bile duct stone, 0.5%; Multiple injuries, 0.5%; and Dermatitis atopic, 0.5%. The registry description states that serious adverse events are summarized regardless of causality. Accordingly, the listed terms do not establish that treatment caused the events. The percentages are registry entries, not comparative estimates.

The record does not report the cause of the death in the registry record, and the death count alone cannot establish its relationship to treatment. It also does not report an analysis comparing these safety observations with a control group. Safety counts are descriptive and should be interpreted within the limits of the open-label, single-group design.

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

The study record establishes that adolescents with moderate-to-severe atopic dermatitis received lebrikizumab in an open-label, single-group study with a stated duration of 52 weeks. It identifies the primary safety-related endpoint as cumulative discontinuation due to one or more adverse events. It also reports participant counts for serious and other adverse events and lists serious-event terms and one death.

Those details do not establish the result of the primary endpoint. The registry record does not report the percentage who discontinued treatment because of adverse events, the number contributing to that endpoint, or an uncertainty interval. The safety counts cannot fill that gap because they measure different outcomes. The record also does not report results for its listed secondary outcomes, so disease response or change cannot be characterized from the outcome names alone.

A single-group study can describe events observed among participants who received the study treatment. Without a comparator, it cannot determine how those outcomes differ from what would occur under another treatment or without treatment. The open-label design is another consideration because knowledge of treatment can influence reporting and assessment. These are limitations of interpretation, not evidence that a particular result is inaccurate.

The safety listings should not be read as proof of causation. The registry says serious events are summarized regardless of causality, and the reported death count does not specify a cause. Likewise, an event's appearance in the registry does not by itself show that it was related to lebrikizumab.

In short, the record describes the population, regimen, study design, endpoint definitions, and certain safety counts. It does not report the primary endpoint result, efficacy estimates, statistical uncertainty, or comparative treatment effects. Conclusions beyond those recorded details would require information not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of the distinction between an outcome definition and an outcome result. The registry specifies a primary endpoint and a follow-up timeframe, but does not report an estimate for that endpoint. Without the estimate, readers cannot assess its magnitude or precision, even though the study is marked completed.

The single-group, open-label design also makes the target of inference important. The available design supports description of the enrolled participants' experience, but not a randomized contrast with another treatment. This distinction is especially relevant when interpreting adverse-event counts: they can describe what was reported during the study, but they cannot establish a comparative risk or treatment causation.

The record lists a range of secondary outcomes, from investigator-rated skin status to patient-reported measures. Different outcomes capture different constructs and may have different scales and analysis needs. The record lists 12 outcome measures but 0 analyses, and does not describe multiplicity handling. This makes it particularly important to distinguish planned or listed outcomes from results that have actually been reported.

Finally, the record's safety counts illustrate why outcome categories must remain separate. Serious adverse events, other adverse events, death, and discontinuation due to adverse events are not interchangeable measures. Clear denominators, endpoint definitions, follow-up rules, and uncertainty estimates are needed to interpret each one. The absence of those result details limits statistical conclusions, regardless of the study's completion status.

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 trial record. The study is open-label and single-group, with no randomized comparator. Any observed outcome rate would therefore be descriptive and would not provide a direct estimate of a difference versus another treatment. The design also does not separate treatment effects from other factors that may influence outcomes in the study population.

The registry record does not report the primary-endpoint result, despite identifying the measure, population, and Week 52 timeframe. It also reports 0 analyses, so no statistical estimates or uncertainty measures are available for the primary or secondary outcomes. The outcome list cannot be treated as evidence that those outcomes were analyzed or that results were favorable or unfavorable.

The record does not report how missing endpoint data were handled, whether all participants completed follow-up, or how discontinuations unrelated to adverse events were treated analytically. It does not report a statistical analysis plan, sample-size justification, multiplicity procedure, or interim analyses. These details should not be inferred from enrollment or completion status.

Safety counts are limited to the categories and information listed. The serious adverse-event summary is described as regardless of causality, and the record does not establish causal relationships. The listed death has no cause stated in the registry record for this account. In addition, safety counts do not answer the primary question about treatment discontinuation due to adverse events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Assess the Safety and Efficacy of Lebrikizumab (LY3650150) in Adolescent Participants With Moderate-to-Severe Atopic Dermatitis — NCT04250350.
• Registry record last updated 2023-02-24; status last verified 2023-01.
• Results first posted 2023-02-24.
• 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

NCT04250350 is a completed Phase 3, open-label, single-group study of lebrikizumab in adolescents with moderate-to-severe atopic dermatitis. The record reports enrollment of 206 and a study duration of 52 weeks. Participants received 250 mg subcutaneously at baseline and Week 2, followed by a single injection every 2 weeks from Week 4 until before Week 52.

The primary endpoint was the cumulative percentage discontinuing study treatment due to one or more adverse events by Week 52, with all enrolled participants identified as the population. The primary result is not reported in the registry record. The safety summary reports 5 participants affected among 206 at risk for serious adverse events, 133 among 206 at risk for other adverse events, and 1 death. The record lists 12 outcome measures and 0 analyses.