A 1-year Trial to Inform About Long-term Exposure to Eptinezumab in Participants With Chronic Cluster Headache (cCH): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A 1-year Trial to Inform About Long-term Exposure to Eptinezumab in Participants With Chronic Cluster Headache (cCH) (NCT05064397), a na phase 3 study. The primary outcome is Number of Participants With Treatment-emergent Adverse Events (AEs).

2. Clinical Question

3. Trial Design

This was a Phase 3 interventional study with an open-label, single-group design. The registry lists 131 participants as enrolled and records the study status as completed. The recorded start date is 2021-09-17, and the primary completion date is 2023-06-29. These dates describe the registry record; they do not by themselves establish how long any individual participant was followed.

Participants received eptinezumab at four planned infusion visits: Baseline (Day 0) and the ends of Weeks 12, 24, and 36. The primary adverse-event timeframe runs from the first dose at Baseline (Week 0) up to Week 56. The intervention is a drug, and the condition listed is chronic cluster headache.

Because the study has no concurrent control group, the design can describe events observed among treated participants but cannot isolate the contribution of treatment from other explanations. Open-label conduct also means the study was not masked. The registry record does not report further details about how outcomes were assessed or how potential observer or reporting effects were handled.

The main stated goal was to inform about long-term safety and tolerability. Several secondary outcomes concern cluster-headache attacks, conversion to an episodic pattern, and use of abortive therapies. The registry lists 29 outcome measures, but does not list analysis results for those measures in the record. The protocol’s rationale for the chosen enrollment, any sample-size justification, and any planned interim analyses are not reported in the registry record.

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: The APTS included all participants who received infusion with eptinezumab.

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 all-participants-treated set (APTS) included all participants who received infusion with eptinezumab.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-emergent Adverse Events (AEs), measured over From the day of first dose of study drug (Baseline [Week 0]) up to Week 56.

The primary endpoint is the number of participants with treatment-emergent adverse events. It is a count of participants, rather than a measure of attack frequency or a direct comparison of treatment groups. The registry defines a treatment-emergent event as an on-treatment untoward medical occurrence in a participant who received study drug. The definition does not require that the event be considered caused by the drug.

The recorded observation period begins on the first-dose day, designated Baseline (Week 0), and extends up to Week 56. This fixed timeframe gives the safety count a defined period of observation. Without a defined period, counts can be difficult to interpret because participants may have different opportunities for events to be recorded.

Safety endpoints are used to describe the types and frequency of adverse events observed during study participation. In this study, the primary endpoint aligns with the stated goal of informing about safety and tolerability during longer-term exposure. A count alone does not indicate severity, duration, clinical importance, or causation for each event. The record also reports separate counts for serious and other adverse events; those categories should be read as descriptive safety information, not as evidence from a randomized comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The posted results are best read as descriptive safety statistics from a single treated group. The primary measure counts participants with treatment-emergent adverse events over a defined observation period. This kind of endpoint is useful for summarizing whether participants experienced an event, but it does not retain all information about the number of episodes, their duration, or their timing.

What does a participant count represent?

A participant count records whether a person meets the endpoint definition during the observation period. It differs from an event count, which may count repeated episodes in the same person. The registry identifies the primary endpoint as a count of participants and defines the relevant event broadly as an on-treatment untoward medical occurrence. That definition does not make a causal claim. An event can be recorded as treatment-emergent even when a causal relationship is not considered possible.

For a count to be interpretable, its population and timeframe matter. The primary safety population is described as participants who received an infusion with eptinezumab. The timeframe is from the day of the first dose at Baseline (Week 0) up to Week 56. The record reports 131 participants at risk for both the serious and other adverse-event counts. It does not report additional information about individual follow-up duration or handling of incomplete observation.

Why does the design affect interpretation?

In a randomized comparison, a treatment group can be compared with a concurrent control group under the trial’s allocation scheme. This study has a single group and no like-for-like control. Its counts therefore describe what was observed among eptinezumab recipients, but cannot distinguish treatment-related risk from the background occurrence of illness, other exposures, or other causes. Open-label conduct means the study was not masked; the registry record does not report procedures to address possible effects of awareness on reporting or assessment.

General statistical context: an estimate of a group’s event frequency is more informative when accompanied by an interval expressing uncertainty. A confidence interval gives a range of values compatible with the data under the statistical method used; it is not a guarantee that the true value lies in that range. No confidence interval for the primary adverse-event count is listed in the registry record, so the precision of a corresponding event-frequency estimate is not reported. A comparative confidence interval would also require a comparator estimate, which this design does not provide.

What do hypothesis tests and recalculations add?

General statistical context: a hypothesis test evaluates how compatible observed data are with a specified null hypothesis under a stated model. A p-value does not measure the size or clinical importance of an effect, and it does not resolve confounding in a non-comparative design. The registry record lists no analysis results for the outcome measures. It therefore does not provide a primary-endpoint p-value or a model-based comparison to interpret.

A simple recalculation from summary statistics can sometimes check an unadjusted comparison or estimate a confidence interval. Such a recalculation depends on the statistics available and cannot replace a sponsor’s own analysis when the posted results disagree. Here, the record does not give a comparative effect estimate or a control-group summary for the primary endpoint, so no unadjusted treatment contrast can be reconstructed from the listed counts.

How should planning illustrations be understood?

General statistical context: sample-size planning asks how many participants a hypothetical study might need to detect an effect under specified assumptions. It is not a statement about the evidence actually observed, and it is not observed power. The registry’s planning description uses a two-sided significance level of 0.05, equal allocation between two hypothetical arms, and a normal approximation; it describes effects as fractions of an observed effect. For non-time-to-event outcomes, such illustrations are expressed as participants per arm. Those assumptions do not turn this single-group study into a two-arm comparison. The registry record does not report the trial’s own sample-size justification or a comparative observed effect on which to base such planning.

General statistical context: over-dispersion occurs when outcome variability exceeds what a chosen statistical model expects. It can make standard errors too small if ignored. The primary endpoint is a participant count, and the record does not report a model or an over-dispersion assessment. No claim about whether over-dispersion was evaluated can be made from the registry record.

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("Eptinezumab")
n      <- c(131)
events <- c(106)
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  Eptinezumab  131  106  80.9  73.1  87.3  73.3  86.7  73.3  86.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 29 outcome measures, including the primary safety endpoint and secondary measures related to headache attacks, conversion from chronic to episodic cluster headache, and use of abortive therapies. When many outcomes are examined, the chance of at least one apparently notable result can increase if each is tested separately without a plan to account for multiplicity. General statistical context: multiplicity procedures define how interpretation or error rates are managed across multiple tests. The registry record does not report a multiplicity strategy, a hierarchy of confirmatory outcomes, or which secondary outcomes were intended to be confirmatory.

The registry lists no analysis results for the outcome measures. It therefore does not report which analysis populations were used for secondary outcomes, whether any adjustment was applied, or how missing outcome observations were handled. The primary safety population is described as including participants who received an infusion, but this does not establish the analysis population for every other endpoint.

General statistical context: missing data can affect estimates when the probability of an observation being missing is related to participants’ outcomes or characteristics. Methods may include assumptions about the missingness process and sensitivity analyses to assess how conclusions change under alternative assumptions. The registry record does not report a missing-data strategy, reasons for missing observations, or sensitivity analyses. It also does not report details of interim analyses or early stopping rules. These omissions limit assessment of how complete outcome follow-up was and how the analysis plan addressed multiple endpoints.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: thyroiditis acute (0.8%), impaired gastric emptying (0.8%), inguinal hernia (0.8%), fatigue (0.8%), cholecystitis acute (0.8%).

The registry reports 11 participants in the serious-adverse-event count and 96 in the other-adverse-event count; 131 participants are listed at risk for each. The record also reports 0 deaths. These numbers describe participants in the eptinezumab group and should not be interpreted as comparisons with another treatment or with no treatment.

The serious-event terms listed are acute thyroiditis, impaired gastric emptying, inguinal hernia, fatigue, acute cholecystitis, and jaw fracture, each reported at 0.8%. Those term-specific percentages are reproduced from the record. They do not establish causation. The treatment-emergent definition includes on-treatment events without regard to whether a causal relationship was considered possible.

Counts for serious and other adverse events should not be added together unless the record establishes that the categories do not overlap. It does not do so in the information. A participant count also does not reveal how many times an event occurred in that person or how long it lasted. The registry record does not report further details needed to interpret event-level course, timing, or attribution for these counts.

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

The results describe adverse events recorded among participants who received eptinezumab in an open-label, single-group study. They give a registry-based account of the number of participants in the serious and other adverse-event categories, the listed serious-event terms, and the death count. This information contributes to a description of observed safety experience over the stated timeframe.

The results do not show what would have happened to the same participants under a different treatment or without eptinezumab. Without a comparator group, the counts cannot separate treatment effects from background events or other influences. They also do not establish that any listed serious-event term was caused by study treatment. The endpoint definition expressly does not require a causal relationship.

The record does not provide a confidence interval or a comparative estimate for the primary endpoint. As a result, it does not quantify the precision of a treatment contrast. The counts also do not fully characterize each event’s severity, duration, recurrence, or clinical course. The registry lists secondary outcomes, but does not report analysis results for them in the information.

General statistical context: a study’s findings apply most directly to the population, treatment schedule, outcome definitions, and follow-up represented in its data. Extending them to other settings requires caution, particularly when the record does not provide detailed eligibility criteria or analysis methods. The completed status and listed enrollment do not resolve these limitations. The statistical meaning is therefore descriptive: the posted figures document recorded events in this study population, not a causal or comparative conclusion about treatment.

14. Why This Trial Matters Statistically

This trial matters statistically because it illustrates the distinction between collecting safety experience and estimating comparative safety. A single-group study can document adverse events during exposure and provide descriptive counts over a defined period. That information is relevant to understanding what was recorded among participants in the study, especially when the stated objective concerns longer-term safety and tolerability.

At the same time, design determines the questions the data can answer. With no concurrent comparator, the study cannot estimate how the observed counts differ from an alternative. Open-label conduct adds another consideration: awareness of treatment may affect reporting or assessment, although the registry record does not describe whether or how this possibility was addressed. These are interpretive constraints, not evidence that any particular event was misclassified.

The endpoint also demonstrates why definitions matter. A treatment-emergent adverse event is defined by its occurrence during treatment, not by proof of causation. Separating temporal association from causal attribution prevents an event count from being mistaken for a count of confirmed treatment-caused events. Similarly, participant counts should not be confused with the number of event episodes.

Finally, the registry lists numerous outcome measures but no analysis results for them. Without reported analysis methods, missing-data handling, multiplicity procedures, or uncertainty estimates, readers cannot assess those aspects of the statistical plan. The study’s value as a descriptive record should be understood alongside these limits on inference.

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 design limitation is the absence of a comparison group. The single-group, open-label design does not support a like-for-like estimate of differences in adverse-event risk, and it cannot determine whether an observed event was caused by eptinezumab. This matters for interpreting both the overall counts and the listed serious-event terms.

The registry record does not report confidence intervals, hypothesis-test results, or a comparative primary-endpoint estimate. It also does not report the trial’s sample-size justification, interim analyses, or the detailed statistical analysis plan. Although the record lists 29 outcome measures, it does not list analysis results for them. The multiplicity strategy and the handling of missing outcome data are not reported in the registry record.

The primary safety population is described as participants who received an infusion, and the endpoint timeframe extends up to Week 56. The record does not report further details about individual follow-up, completeness of event ascertainment, or event-level timing and causality assessments. The reported participant counts do not establish whether serious and other adverse-event categories overlap.

These limitations restrict causal and comparative interpretation. They do not invalidate the descriptive counts, but they define what those counts can support: a record of reported events in the study population under the stated design and endpoint definition.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A 1-year Trial to Inform About Long-term Exposure to Eptinezumab in Participants With Chronic Cluster Headache (cCH) — NCT05064397.
• Registry record last updated 2024-08-06; status last verified 2024-07.
• Results first posted 2024-08-06.
• 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.

19. Record Summary

The registry describes a completed Phase 3, open-label, single-group study of eptinezumab in chronic cluster headache. It lists 131 enrolled participants and four planned intravenous infusions at Baseline (Day 0) and the ends of Weeks 12, 24, and 36. The primary safety timeframe runs from the first dose at Baseline (Week 0) up to Week 56.

The primary endpoint counts participants with treatment-emergent adverse events. The record reports 11 participants in the serious-adverse-event count, 96 in the other-adverse-event count, and 0 deaths, with 131 at risk in each category. Six serious-event terms are listed at 0.8% each. These are descriptive results; no control group, comparative estimate, or primary-endpoint confidence interval is reported. The registry lists 29 outcome measures but no analysis results for them. The protocol’s sample-size justification, missing-data methods, multiplicity strategy, and interim analyses are not reported in the registry record.