Open-label Multi-site Extension Trial in Subjects Who Completed the DELTA 1 or DELTA 2 Trials: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Multi-site Extension Trial in Subjects Who Completed the DELTA 1 or DELTA 2 Trials (NCT04949841), a na phase 3 study. The primary outcome is Number of Treatment-emergent Adverse Events From Baseline up to Week 38.

2. Clinical Question

DELTA 3 was designed to evaluate long-term safety after participation in DELTA 1 or DELTA 2. Its open-label extension format follows participants receiving the study cream without a concurrent control arm. The clinical question is therefore descriptive: what adverse events were recorded during the treatment and follow-up period, and what patterns of eczema measures were tracked?

The record lists 801 enrolled participants. That number describes the extension’s enrollment; it does not by itself establish how many participants contributed information to every outcome or visit. The posted adverse-event figures give denominators for the listed safety summaries, while the registry record does not provide a primary endpoint event total.

3. Trial Design

DELTA 3 is a Phase 3, open-label, single-group extension trial sponsored by LEO Pharma. Its official title describes an extension of DELTA 1 and DELTA 2 to evaluate long-term safety of twice-daily delgocitinib cream 20 mg/g as needed for up to 36 weeks in adults with chronic hand eczema. Participants had completed one of the preceding trials. There was no randomized allocation and no masking.

The registry lists enrollment of 801 and classifies the trial status as completed. The recorded start date is 2021-08-23, and the primary completion date is 2023-09-18. These dates describe the trial record; they do not show when an individual participant began or finished treatment.

Participants were treated with delgocitinib cream twice daily as needed. Clinic visits were planned every 4 weeks to assess safety and efficacy through Week 36, followed by a final phone follow-up planned for Week 38. The primary outcome is the number of treatment-emergent adverse events from baseline up to Week 38. The record defines an event as treatment emergent when it started after baseline.

Secondary outcomes include IGA-CHE scores at scheduled visits, the number with an IGA-CHE score of 0 (Clear) or 1 (Almost Clear), HECSI scores, and the number meeting HECSI-75 or HECSI-90. Those measures describe eczema status or change thresholds, but outcome results for them are not reported in the registry record.

Because all participants received the study treatment and the trial was open label, observed changes over time cannot be separated from other influences using a randomized concurrent comparison. The extension’s design is suited to describing experience during continued treatment in this selected group, but it does not establish how the same participants would have fared under an alternative treatment or without treatment.

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: This trial enrolled subjects who completed one of the 2 pivotal phase 3 trials with delgocitinib cream 20 mg/g or cream vehicle (parent trials - Trial 1401 \[NCT04871711\] or Trial 1402 \[NCT04872101\]).

Overall Study

Reasons for not completing this period:

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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Treatment-emergent Adverse Events From Baseline up to Week 38, measured over From baseline up to Week 38.

The primary endpoint is the number of treatment-emergent adverse events from baseline up to Week 38. The registry defines treatment emergent by timing: an adverse event qualifies if it started after the baseline visit. The endpoint therefore concerns events arising during the post-baseline observation period, rather than every health event a participant may have experienced at any time.

Counting events can help describe the amount of reported safety experience over a specified period. It is not the same as counting participants with at least one event: a participant may experience more than one event, so event totals and participant totals answer different questions. The registry’s primary endpoint is stated in events, while the posted adverse-event summary separately gives numbers of participants affected by serious and other adverse events.

The endpoint is relevant to a long-term safety extension because ongoing exposure creates an opportunity to observe events during continued treatment and follow-up. However, a count alone does not convey the event’s duration, severity, relationship to treatment, or clinical course unless those details are separately reported.

The primary endpoint result itself is not reported in the registry record. Thus, the endpoint definition can be described, but its total event count and any estimate of uncertainty around that count cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help clarify what the registry record can support. The methods are general explanations; they do not assert that a particular unreported method was used in DELTA 3.

What does a single-group design estimate?

A single-group study describes outcomes among people who received the study treatment. It can report how many events occurred or how many participants were recorded with an event. Without a concurrent comparison group, however, it cannot directly estimate the difference between treatment and control outcomes. Participants’ health may change over time for reasons other than treatment, and the study design does not distinguish those influences from treatment-related change.

That limitation is particularly important for causal interpretations. A count of events during treatment is a description of what was recorded during follow-up. It is not, on its own, evidence that treatment caused those events or prevented other events. Causal conclusions generally require a credible comparison and assumptions that address differences between groups. DELTA 3 has no randomized comparison group, and the registry record does not report a substitute comparison strategy.

Why distinguish events from participants?

An event count and a count of affected participants describe different quantities. A participant can have multiple events, so an event total may exceed the number of participants with at least one event. Conversely, a participant count summarizes whether a person was affected, without showing how many events that person experienced. The primary endpoint is defined as a number of treatment-emergent events, while the safety summary reports participants with serious adverse events and participants with other adverse events. Those summaries should not be treated as interchangeable.

Event counts also need a time frame and a clear event definition. Here the endpoint covers baseline up to Week 38, and an event qualifies as treatment emergent if it began after baseline. The definition identifies timing, but it does not by itself establish causality, severity, or whether events were recurrent. Those features require additional reporting.

What would a confidence interval mean?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model and its assumptions. A narrower interval indicates greater precision under that model; a wider interval indicates more uncertainty. For event counts, the appropriate interval depends on how the events were generated and on whether repeated events within participants are accounted for. A simple model that treats all events as independent may understate uncertainty if events cluster within people.

The registry record does not report a confidence interval for the primary endpoint, nor does it report the primary event total. Therefore, no precision estimate for that endpoint can be interpreted. A confidence interval would not resolve the lack of a control group: precision about an observed group’s event experience is different from evidence about a treatment-versus-control effect.

Why can over-dispersion matter?

For count outcomes, a model may assume a particular relationship between the average count and its variability. Over-dispersion means the observed variation is greater than the model expects. It can arise when some participants have more events than others or when events are clustered, and it can make standard errors and confidence intervals too optimistic if the model does not allow for that extra variation. This is a general issue for repeated or clustered event data, not a claim that over-dispersion was present in DELTA 3. The registry record does not report a count model, a dispersion estimate, or a method for handling repeated events.

How should the planning illustrations be read?

Planning illustrations based on an observed effect are not observed power. They use assumptions to show how a future study might be planned to detect a chosen fraction of an effect. The stated assumptions for these illustrations are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a fraction of the observed effect. For time-to-event tables, the stated quantity is the total number of events; for other outcomes, it is participants per arm.

These are planning assumptions, not a description of DELTA 3’s design. DELTA 3 is a single-group extension with no randomized two-arm comparison, and its outcome type is a count rather than a single comparison. The registry record does not report a trial-specific sample-size justification. Accordingly, planning results based on an observed effect should not be interpreted as evidence that DELTA 3 had a particular probability of detecting an effect, or as a substitute for a controlled design.

What can secondary outcomes contribute?

Secondary outcomes can describe additional aspects of a condition, such as scores at scheduled visits or the number of participants reaching a specified response threshold. In general, repeated measures can show how recorded outcomes vary over time, while threshold outcomes classify participants according to whether a criterion is met. Interpretation depends on the exact scoring rules, analysis population, handling of missing visits, and statistical methods.

The registry names IGA-CHE and HECSI outcomes, including HECSI-75 and HECSI-90, but the results and analysis methods are not reported in the registry record. Their presence in the outcome list does not establish a result or a statistically significant change. Nor can the posted safety counts fill in those missing efficacy results.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes: IGA-CHE scores at scheduled visits, the number with an IGA-CHE score of 0 (Clear) or 1 (Almost Clear), HECSI scores, and the numbers meeting HECSI-75 or HECSI-90. Assessing multiple outcomes or multiple visits raises a general multiplicity issue: the more statistical tests undertaken, the greater the chance that at least one result may appear noteworthy by chance if each is interpreted without adjustment. Whether and how to control that risk depends on the prespecified analysis strategy.

A multiplicity strategy is not reported in the registry record. The record also does not report an analysis plan, analysis populations, or results for the listed secondary outcomes. The primary endpoint event total and its statistical uncertainty are likewise not reported in the record. These omissions prevent assessment of the planned testing hierarchy or of how reported findings, if any, were selected and interpreted.

Missing data can also affect repeated-visit outcomes. In general, participants may miss visits or discontinue follow-up, and estimates can be biased if the people with available measurements differ systematically from those without them. Methods such as complete-case analysis or imputation rely on assumptions, and those assumptions should be made explicit. The registry’s visit schedule does not establish which observations were available or how missing measurements were handled. Missing-data methods, reasons for missingness, and analysis populations are not reported in the registry record.

11. 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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hand dermatitis (0.2%), myocardial infarction (0.1%), abdominal incarcerated hernia (0.1%), abdominal pain upper (0.1%), food poisoning (0.1%).

The posted safety summary lists 27 participants with serious adverse events, 329 with other adverse events, and 3 deaths, with an at-risk denominator of 801 for each listed category. These are participant figures for the treated group. They are distinct from the primary endpoint, which is defined as the number of treatment-emergent adverse events through Week 38; that event total is not reported in the registry record.

The registry lists serious-event terms with percentages: Hand dermatitis, 0.2%; Myocardial infarction, 0.1%; Abdominal incarcerated hernia, 0.1%; Abdominal pain upper, 0.1%; Food poisoning, 0.1%; and Death, 0.1%. These entries should be read as the listed terms and percentages, not as a complete account of all adverse events. The record does not give the term-specific counts or details about timing, duration, outcome, or relationship to treatment in the information.

Serious adverse events are not necessarily events caused by treatment. The single-group, open-label design cannot determine whether the observed event frequency differs from what would have occurred under another treatment or without treatment. The counts describe the registry’s safety summary; they do not establish a causal effect.

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

DELTA 3 provides a record of an open-label extension in adults with chronic hand eczema who completed DELTA 1 or DELTA 2. Participants received delgocitinib cream 20 mg/g twice daily as needed, with planned clinic assessment through Week 36 and a follow-up phone call planned for Week 38. The record’s primary safety question concerns treatment-emergent adverse events over the period from baseline up to Week 38.

The posted safety summary records participants with serious adverse events, participants with other adverse events, and deaths, and lists selected serious-event terms and percentages. Those observations describe safety experience in the treated group. They do not, by themselves, show that treatment caused an event or establish whether the event frequency was higher or lower than it would have been under a comparator.

The trial does not include a randomized control group, and participants and investigators were not masked. There is therefore no like-for-like concurrent comparison from which to estimate a treatment effect. The selected extension population—people who completed DELTA 1 or DELTA 2—also differs from a population recruited independently for a new trial, so the findings describe this extension group rather than automatically applying to all adults with chronic hand eczema.

The primary endpoint is a count of events, but its total is not reported in the registry record. The registry lists secondary eczema measures, but their results are also not reported in that record. As a result, the listed design and safety figures do not support a conclusion about the size or precision of the primary endpoint, or about changes in eczema scores.

These limitations do not erase the descriptive value of a long-term extension. They define what its record can establish: the study design, planned observation period, endpoint definitions, and posted safety summaries. They also clarify what remains unknown from the registry record, including comparative safety, causal attribution, and the unreported endpoint and secondary-outcome results.

13. Why This Trial Matters Statistically

Extension trials address a different statistical question from randomized efficacy trials. They can document safety experience during continued treatment among participants who completed earlier trials, and can follow planned outcomes over an extended period. DELTA 3’s record identifies that purpose and specifies a safety endpoint extending from baseline up to Week 38.

Statistically, the distinction between descriptive follow-up and comparative inference is central. A single-group study can report observed events, but it cannot directly estimate what would have happened to the same participants under a different treatment. This matters when reading adverse-event counts: they are important descriptions of the treated group, not comparative evidence of excess risk or protection.

The endpoint also illustrates why outcome definitions matter. The primary measure counts treatment-emergent events, while the posted safety figures count affected participants in event categories. Those measures answer different questions and should not be conflated. The primary count itself is not reported in the registry record, limiting assessment of the stated primary endpoint.

Finally, the trial record distinguishes planned outcomes from available results. Naming IGA-CHE and HECSI measures tells readers what the study intended to assess, but does not show the observed values or how missing measurements and multiple outcomes were handled. Clear reporting of event totals, analysis populations, uncertainty, and analysis methods would be needed for a fuller statistical interpretation.

14. 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 main design limitation is the absence of a concurrent control group. Because DELTA 3 is a single-group extension with no randomized allocation or masking, the record cannot establish a treatment-versus-control contrast or separate treatment effects from other changes over time. Open-label assessment may also influence how events or clinical outcomes are reported and evaluated.

The study population consists of adults who completed DELTA 1 or DELTA 2. This is a selected extension population, and the registry record does not provide details that would show how its experience compares with people who did not complete the earlier trials or with a broader population of adults with chronic hand eczema.

The primary endpoint is defined, but its event total is not reported in the registry record. The record also does not report results for the listed secondary outcomes, analysis populations, handling of missing observations, or the statistical methods used for outcome analyses. These gaps prevent evaluation of endpoint precision, visit-level completeness, and the robustness of any outcome analysis.

The adverse-event summary is informative as a group description, but the record does not give further details for the listed serious-event terms, such as their timing, duration, outcome, or relationship to treatment. Participant counts should not be mistaken for total event counts. Finally, the registry record does not report a trial-specific sample-size justification, interim analyses, or a statistical analysis plan.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Open-label Multi-site Extension Trial in Subjects Who Completed the DELTA 1 or DELTA 2 Trials — NCT04949841.
• Registry record last updated 2025-04-08; status last verified 2024-11.
• Results first posted 2025-01-20.
• 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.

18. Record Summary

NCT04949841 is a completed Phase 3, open-label, single-group extension trial sponsored by LEO Pharma. It enrolled 801 adults with chronic hand eczema who had completed DELTA 1 or DELTA 2. Participants received delgocitinib cream 20 mg/g twice daily as needed for up to Week 36, with a final follow-up phone call planned for Week 38.

The primary endpoint is the number of treatment-emergent adverse events from baseline up to Week 38; the registry defines these as events starting after baseline. The primary event total is not reported in the registry record. The posted safety summary lists 27 participants with serious adverse events, 329 with other adverse events, and 3 deaths, with 801 at risk in each listed category.

The registry also lists IGA-CHE and HECSI secondary outcomes, but their results are not reported in the record. The single-group design supports descriptive interpretation, not a randomized comparison or causal estimate.