Safety Study of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety Study of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis (NCT04991935), a na phase 3 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAE).

2. Clinical Question

This study asks a safety question about continued treatment with CC-93538 in adults and adolescents with eosinophilic esophagitis. It is an open-label extension: participants had taken part in the CC-93538-EE-001 or CC-93538-DDI-001 studies, and the extension was intended to evaluate long-term safety and tolerability. The primary outcome is the number of participants with treatment-emergent adverse events, assessed from the first dose until study completion, early discontinuation, or loss to follow-up, whichever occurred first, for up to approximately 36 months.

The registry describes one treatment group receiving CC-93538, administered subcutaneously once weekly. With no concurrent control group, the study can describe adverse events observed among participants during follow-up, but it cannot directly compare their frequency with that in an untreated group or another treatment group. Open-label status also means the study was not masked.

The registry record lists an enrollment of 367 and a study status of completed. Those details describe the scale and status of the study, not the frequency of the primary outcome. The available adverse-event summary gives separate counts for serious and other adverse events, but does not identify either count as the reported result for the primary endpoint.

3. Trial Design

This is a Phase 3, multicenter, multinational, open-label extension study of CC-93538 in adults and adolescents with eosinophilic esophagitis. Its stated purpose is to evaluate long-term safety and tolerability. The registry lists the design as single-group, with allocation not applicable and masking none. The treatment group is listed as CC-93538 360 mg QW, and the administration description says participants received CC-93538 subcutaneously once weekly.

The extension enrolled participants who had taken part in the CC-93538-EE-001 or CC-93538-DDI-001 studies. Enrollment was 367. The registry lists a start date of 2022-08-09, a primary completion date of 2025-08-14, and a status of completed. The primary endpoint timeframe is from first dose until study completion, early discontinuation, or loss to follow-up, whichever occurs first, for up to approximately 36 months.

Because everyone is described within one treatment group and there is no concurrent control, this design is suited to recording events during exposure and follow-up, not to estimating a randomized treatment contrast. Its open-label nature also means participants and investigators were not masked to treatment. The registry record does not report details of visit schedules, dose interruptions, treatment changes, eligibility criteria beyond the extension-study participation, or the duration of follow-up for individual participants.

The record lists four outcome measures and names the number of participants with treatment-emergent anti-CEN antibodies as a secondary outcome. It does not report a statistical analysis count. A single-group safety record can show what adverse events were recorded in the enrolled group, but the design cannot separate treatment-related effects from events that could occur because of the underlying condition, participants' prior study history, or other factors. The registry record does not report a formal comparative safety analysis.

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: Participants were enrolled in 14 countries.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Open label extension population included all the 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.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment Emergent Adverse Events (TEAE), measured over From first dose until study completion, early discontinuation, or loss of follow up, whichever occurs first (Up to approximately 36 months).

The primary endpoint is the number of participants with treatment-emergent adverse events (TEAEs). It is expressed as a count of participants, rather than a continuous measurement. The registry defines an adverse event as a new untoward medical occurrence or worsening of a pre-existing medical condition in a participant administered study treatment; the event does not necessarily have to be causally related to treatment. A serious adverse event is defined by outcomes such as death, a life-threatening event, inpatient hospitalization, or prolongation of an existing hospitalization.

Counting participants with an event is a common way to describe safety in a treatment group. It answers how many people experienced at least one event during the specified observation period, rather than how many total event episodes occurred. The registry's timeframe begins at the first dose and ends at study completion, early discontinuation, or loss to follow-up, whichever occurs first, with follow-up described as up to approximately 36 months.

As a general statistical point, a participant count is easiest to interpret alongside the number of participants observed and the length and completeness of their follow-up. Participants followed for different lengths of time may have different opportunities for events to be recorded. The registry record does not report a primary-endpoint count, an event rate over person-time, or the distribution of individual follow-up durations. The adverse-event summary lists serious and other adverse-event counts, but it does not establish either count as the posted primary TEAE result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General concept: A single-group safety study describes events among participants receiving the study treatment. It can document the kinds of events recorded and the number of participants affected, but without a concurrent comparator it cannot estimate a randomized difference between treatment strategies. This extension is listed as single-group, open-label, and without masking; allocation is not applicable. Its design should therefore be read as descriptive rather than as a controlled comparison.

What does a count of participants measure?

The primary outcome is a count of participants with treatment-emergent adverse events. A participant count is different from an event count: one participant may experience more than one event, while a count of participants ordinarily concerns people who experienced an event. The registry title specifies participants, and its unit is participants. The primary endpoint result itself is not reported in the registry record. The separate adverse-event summary reports 25 participants with serious adverse events and 158 with other adverse events; those figures should not be substituted for the missing primary-endpoint result because the record does not state that they represent the same endpoint definition.

The primary timeframe starts at first dose and continues until study completion, early discontinuation, or loss to follow-up, whichever occurs first, for up to approximately 36 months. A fixed maximum timeframe does not mean every participant contributed the same amount of observation. As a general statistical point, unequal follow-up can affect the chance that an event is observed. Event rates using person-time can address differences in observation time, but the registry record does not report a person-time analysis or participant-level follow-up durations.

Why does the design affect interpretation?

Random allocation and a concurrent comparator can help distinguish treatment-group differences from other explanations, when those features are part of a study. They are not present in this record: the study is single-group, open-label, and has no like-for-like control comparison. Thus, the adverse-event counts describe the extension cohort and cannot quantify a difference attributable to CC-93538. The extension participants also came from earlier CC-93538 studies, so this is a selected extension population rather than an account of all people with eosinophilic esophagitis.

Open-label status means treatment assignment was not masked. As a general concept, knowledge of treatment can affect reporting, recognition, or classification of subjective symptoms, even when the event definition is specified. The registry record does not report procedures intended to reduce such effects, so their use should not be assumed.

What can be said about uncertainty?

Confidence intervals are a general way to express statistical uncertainty around an estimate. They indicate a range of values compatible with the data under the analysis assumptions; they do not by themselves correct for bias or create a comparison group. No confidence intervals or inferential analyses are reported in the registry record. Consequently, the precision of the reported adverse-event counts cannot be described using reported interval estimates.

The record lists 367 participants at risk for the serious-event summary and 367 at risk for the other-event summary. A denominator helps put a count in context, but it does not disclose differences in follow-up time or missing observations. The record does not provide additional details about how incomplete follow-up was handled in the adverse-event summaries.

How should significance and power be understood?

The registry record reports no inferential analyses, so it supplies no p-value or test of a treatment contrast. As a general statistical concept, a p-value is interpreted relative to a specified null hypothesis and analysis; it is not a measure of clinical importance or proof that a result is true. In a single-group descriptive safety record, a p-value would not replace the missing comparator needed to estimate a between-group effect.

Any planning illustration based on detecting an effect is not the study's own design or an observed-power calculation. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of an observed effect. Those assumptions describe a hypothetical two-arm planning framework, unlike this single-group extension. No numerical planning results are reported in the registry record. As a general concept, sample-size planning depends on the design and assumptions chosen; a planning illustration should not be presented as the number actually needed or enrolled in this study.

Why are adverse-event categories not interchangeable?

The registry distinguishes serious adverse events from other adverse events in its summary, while the primary endpoint is titled as the number of participants with TEAEs. The serious-event definition is based on specified consequences, while the general AE definition includes new or worsening medical occurrences without requiring a causal relationship. These labels serve different purposes. Without an explicit mapping in the registry record, it is not appropriate to treat the serious and other-event counts as exhaustive, mutually exclusive pieces of the primary endpoint. The record also does not state how recurrent events or participants with multiple event types were handled in any analysis.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists four outcome measures and identifies the number of participants with treatment-emergent anti-CEN antibodies as a secondary outcome. It does not report results for that secondary outcome in the registry record, nor does it describe a prespecified hierarchy of outcomes or a method for controlling multiplicity. A multiplicity procedure is not reported in the registry record.

Multiplicity matters when several outcomes or statistical tests are interpreted together: the chance of at least one apparently unusual finding can increase as more tests are considered. This is a general statistical concern, not evidence that a particular procedure was or was not used in the study. The record reports zero analyses, so no inferential testing results or adjustment procedure can be assessed from the posted information.

The record defines the primary outcome timeframe as extending until study completion, early discontinuation, or loss to follow-up, whichever occurs first. It does not report a method for handling missing outcome data, incomplete follow-up, or participants who discontinue early. The extension population is described as including all enrolled participants, but the analysis population used for each outcome is not separately detailed. The record also does not report participant flow by outcome or the number with complete follow-up.

As a general statistical matter, missing data methods can affect estimates when observation is incomplete, especially if the likelihood of missingness is related to participants' health or event experience. Without information on missingness and its handling, the impact cannot be evaluated. The registry record does not report interim analyses, and no interim-analysis plan should be inferred from the completed status alone.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: anaphylactic reaction (1.4%), eosinophilic oesophagitis (0.5%), atrial fibrillation (0.3%), abdominal pain (0.3%), oesophageal rupture (0.3%).

The registry's adverse-event summary reports 25 participants with serious adverse events among 367 at risk and 158 participants with other adverse events among 367 at risk. It reports 0 deaths. These are descriptive counts for the CC-93538 360 mg QW group, not comparisons with a control group. The record does not say that the serious and other-event categories are mutually exclusive, so the counts should not be combined.

The listed serious-event terms are anaphylactic reaction (1.4%), eosinophilic oesophagitis (0.5%), atrial fibrillation (0.3%), abdominal pain (0.3%), oesophageal rupture (0.3%), and pancreatitis (0.3%). These percentages are reported as serious-event terms; the registry does not give corresponding counts for each term in the registry record. It also does not say whether participants could have more than one term recorded.

Seriousness is a classification based on consequences such as death, life threat, inpatient hospitalization, or prolonged hospitalization, as defined in the registry. It is distinct from whether an event was caused by treatment. The AE definition does not require a causal relationship. The registry does not report causal assessments for these events, individual exposure time, or a concurrent comparison group. Accordingly, these figures describe events recorded during the extension but do not establish their cause or quantify a comparative risk.

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

The study documents a long-term safety extension in a defined group of adults and adolescents with eosinophilic esophagitis who had participated in earlier CC-93538 studies. It enrolled 367 participants and used an open-label, single-group design. The adverse-event summary reports 25 participants with serious adverse events, 158 with other adverse events, and 0 deaths. These observations can help readers understand what was recorded during the extension, while the registry's definitions and follow-up period clarify what the counts are intended to describe.

The record does not report the primary endpoint result, which is the number of participants with treatment-emergent adverse events. Nor does it provide inferential analyses, confidence intervals, or a comparator group. The adverse-event summary does not fill those gaps: the relationship between the serious and other-event categories and the primary endpoint is not specified, and no causal attribution is required by the AE definition.

As a general statistical interpretation, an observed count is not the same as a treatment effect. A treatment effect would require a defined comparison and an estimate of the difference or another contrast, together with its uncertainty. This study's single-group design cannot directly provide that comparison. Also, the reported counts alone do not show how long each participant was followed or whether event opportunities differed across participants.

The results therefore do not establish that CC-93538 caused a particular event, that the event frequency was higher or lower than under another treatment, or that all possible safety outcomes were captured in the posted summary. They also do not answer an efficacy question: the stated purpose is long-term safety and tolerability, and the available outcome information does not report a treatment-effect analysis. The findings are best understood as descriptive safety information for the enrolled extension population, with important limits on comparison and precision.

13. Why This Trial Matters Statistically

This trial is statistically notable because it shows the role and limits of an open-label extension in safety assessment. Extending observation in participants who took part in earlier studies can document events during continued treatment and provide descriptive information beyond an initial study period. Here, the registry describes follow-up from the first dose until study completion, early discontinuation, or loss to follow-up, whichever occurred first, for up to approximately 36 months.

The same design features that make the study an extension shape what can be inferred. It is a single-group study without a concurrent control, so its counts cannot estimate a randomized contrast. The registry defines an adverse event without requiring that it be caused by the study treatment, making it especially important to separate event recording from causal interpretation. Open-label status and variable individual follow-up are also relevant when reading descriptive safety data.

Statistical reporting matters as much as the design. The registry identifies the primary TEAE outcome but does not report its result, and it supplies no confidence intervals or inferential analyses. The separate serious and other-event counts offer some descriptive information, but the record does not explain their overlap or their relationship to the primary outcome. Those distinctions prevent a reader from treating the counts as a complete primary-endpoint analysis.

More broadly, the study illustrates that a sizeable enrollment and a completed status do not by themselves establish precision or causality. A clear denominator helps contextualize counts, but information about individual observation time, missing data, and analysis methods is also important. The available record supports a careful description of the extension's design and posted safety counts, while leaving comparative and inferential questions unresolved.

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 principal limitation is the absence of a concurrent control group. The registry lists a single-group, open-label design with allocation not applicable and masking none. Consequently, adverse-event counts cannot show how event frequency compares with another treatment or with no study treatment. The AE definition also does not require causal relation to treatment, so an event's occurrence alone does not establish that CC-93538 caused it.

The primary outcome is defined, but its result is not reported in the registry record. The available safety summary includes serious and other adverse-event counts, but the record does not state how those categories relate to the primary TEAE outcome or whether they overlap. It does not provide confidence intervals, p-values, event rates by person-time, or inferential analyses. The precision of the counts and the size of any comparative effect therefore cannot be evaluated from the posted information.

Although the timeframe extends up to approximately 36 months, the registry record does not report each participant's follow-up duration, the handling of early discontinuation or loss to follow-up, or missing-data methods. It also does not report detailed participant flow or the analysis population for each outcome. These omissions limit assessment of how completely the observed events represent the enrolled group over time.

The extension enrolled participants from two earlier studies, so the findings describe that extension population rather than an unselected population with eosinophilic esophagitis. The record does not provide further details about participant characteristics, concomitant care, dose changes, or event adjudication. These details should not be assumed. Finally, the record lists several outcomes but does not report results for all of them or describe multiplicity handling. Taken together, the available information permits a limited descriptive reading of safety observations, not a causal or comparative conclusion.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Safety Study of CC-93538 in Adult and Adolescent Participants With Eosinophilic Esophagitis — NCT04991935.
• Registry record last updated 2026-04-06; status last verified 2026-03.
• Results first posted 2026-04-06.
• 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

The registry record describes NCT04991935, a Phase 3, multicenter, multinational, open-label extension study of CC-93538 in adults and adolescents with eosinophilic esophagitis. Its official title identifies the study as an evaluation of long-term safety. The sponsor is Celgene. The study is listed as completed, with a start date of 2022-08-09 and a primary completion date of 2025-08-14.

The study enrolled 367 participants from the CC-93538-EE-001 or CC-93538-DDI-001 studies. It is a single-group design with no masking and no concurrent comparator. The treatment group is listed as CC-93538 360 mg QW, administered subcutaneously once weekly. The primary outcome is the number of participants with treatment-emergent adverse events, assessed through the stated follow-up period.

The adverse-event summary reports 25 participants with serious adverse events, 158 with other adverse events, and 0 deaths among 367 at risk. A primary-endpoint result and inferential analyses are not reported in the registry record.