An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of Subjects With Batten Ceroid Lipofuscinosis, Neuronal 3 (CLN3) Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of Subjects With Batten Ceroid Lipofuscinosis, Neuronal 3 (CLN3) Disease (NCT05174039), a na phase 1, phase 2 study. The primary outcome is Number of Treatment-emergent Adverse Events..

2. Clinical Question

In practical terms, the record describes a small, uncontrolled study focused on safety, pharmacokinetics, and efficacy-related measures. The primary question is about adverse events among participants receiving miglustat; it is not a comparison of event rates between treatment and control groups. The posted adverse-event figures list participant counts, including participants with serious and other adverse events. Those counts provide a descriptive account of events recorded in this group, but they do not establish what would have occurred without miglustat.

Because the study is open label and has no comparator, observations on clinical outcomes are also difficult to separate from the natural course of CLN3 disease, measurement variation, or other influences. The registry record does not report numerical efficacy findings or a statistical comparison for the listed efficacy outcomes. The clinical question can therefore be described from the design and endpoint, while the record does not establish a comparative estimate of efficacy.

3. Trial Design

This is a phase 1 and phase 2, open-label, single-group study of oral miglustat in people with CLN3 disease who are 17 years of age and older. The registry lists enrollment of 6. It describes an intended study of approximately 6 subjects at 2 centers, with a study period of 104 weeks. The listed study start date is 2022-03-10, the primary completion date is 2024-05-30, and the status is completed.

The intervention is oral miglustat. The proposed regimen is daily oral dosing at the maximum tolerated dose, up to 200 mg three times daily; the brief summary gives a range from 100 mg once daily to 200 mg three times daily. The record does not describe a control intervention. Allocation is listed as not applicable, masking is none, and the model is single group. These features mean the study is not a randomized or masked comparison against another treatment or control condition.

The primary outcome is the number of participants with treatment-emergent adverse events, with a 78-week timeframe. The description says events were assessed at visits and phone calls and that severity was classified according to CTCAE v5.0. Listed secondary outcomes include miglustat pharmacokinetic measures—Cmax, Tmax, area under the curve, and half-life—as well as clinical efficacy based on Unified Batten Disease Rating Scale subscores and seizure frequency. The record lists 7 outcome measures, but numerical results for the secondary outcomes are not reported in the registry record.

The study’s design can support descriptive reporting about the participants treated and the events recorded. Without a comparator group, it cannot provide a randomized estimate of the difference attributable to miglustat. The registry record does not report the rationale for the enrollment target, details of dose changes or treatment exposure, or a statistical analysis plan. Those omissions limit interpretation of how the planned assessments were intended to address the study questions.

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 had their first enrolment visit to determine their eligibility, then a second visit within the next 42 days to confirm eligibility and perform baseline efficacy assessments. If eligibility was confirmed at the second visit, they started treatment within the next 15 days after this visit.

Overall Study

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: 6

6. Primary Endpoint

The registry lists the primary outcome as Number of Treatment-emergent Adverse Events., measured over 78 weeks.

The primary endpoint is the number of participants with treatment-emergent adverse events, assessed over 78 weeks. The record says events were assessed at all visits and phone calls, and severity was classified according to CTCAE v5.0. This endpoint is intended to describe safety during treatment by recording adverse events that emerge after treatment begins. Reporting the number of affected participants is a way to summarize how many people experienced an event, rather than describing only the total number of event episodes.

The endpoint title refers to the number of treatment-emergent adverse events, while its unit and parameter specify participants and a count of participants. That distinction matters: participant counts do not necessarily indicate how many separate episodes occurred, whether a participant had repeated events, or how long events lasted. The posted adverse-event figures are likewise participant counts by category. They should not be interpreted as a complete account of event frequency or severity beyond the categories and details recorded.

Safety is an appropriate focus for a study whose stated objectives include assessment of safety and whose dosing is described as a maximum-tolerated-dose regimen. However, the registry record does not report the endpoint’s full operational definition, such as the precise criteria used to classify an event as treatment-emergent, nor does it report how events were attributed to treatment. The primary endpoint timeframe is 78 weeks, while the overall study period is described as 104 weeks; the registry record does not explain the relationship between those periods. Thus, the endpoint identifies the intended safety measure, but the posted information does not resolve every detail needed to reconstruct its analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

General explanation: A single-group study observes outcomes among people receiving an intervention without a concurrent comparison group. It can describe what happened in the observed group, but it cannot directly estimate how outcomes would have differed under an alternative treatment or no treatment. Random allocation is one way to make groups comparable in expectation; this study has no allocation and is not randomized according to the registry record.

For this study, the posted adverse-event counts describe the Oral Miglustat group. They are not a contrast between miglustat and a control condition. Differences from other studies, if someone makes such a comparison, could reflect differences in participants, follow-up, event definitions, or reporting. The registry record does not provide a controlled comparison that would resolve those possibilities.

What does open-label mean for interpretation?

General explanation: In an open-label study, treatment assignment is not masked from participants and study personnel. Knowledge of treatment can influence reporting, clinical assessment, or decisions about evaluation, although the direction and size of any such influence cannot be determined from the design label alone. Masking is listed as none. The registry record does not describe additional procedures intended to reduce observer or reporting influences.

This design feature does not invalidate the event counts, but it is relevant to how they are interpreted. Safety events may include observations reported by participants and assessments made during study contact. The record says assessments occurred at visits and phone calls, but does not provide further detail on event ascertainment procedures.

How should participant counts be read?

General explanation: A count of participants with an event answers how many people experienced at least one event under the stated definition. It is different from a count of event episodes, since a participant may have repeated events. Participant counts also do not describe event duration or severity unless those features are reported separately. For this endpoint, the listed unit is participants and the parameter is a count of participants.

The posted figures therefore describe affected participants by the reported adverse-event categories. The record does not give a full event-level listing or a participant-level account that would show overlap between categories. The serious-event terms are listed with percentages, but the record does not specify additional detail about episodes or recurrence in the information summarized for this endpoint.

What does a confidence interval communicate?

General explanation: A confidence interval expresses statistical uncertainty around an estimate under the assumptions of the analysis. A narrower interval indicates greater precision in that estimate, while a wider interval indicates less precision. An interval does not remove possible bias from study design, measurement, or missing data, and it does not establish that an observed association is causal.

The registry record does not report a confidence interval for the primary endpoint or the listed adverse-event counts. It also does not report a comparative estimate. A confidence interval cannot be reconstructed from the available counts without additional assumptions and information, so no interval should be inferred from the percentages or participant counts.

Why does the analysis plan matter?

General explanation: A statistical analysis plan specifies how outcomes are defined and analyzed, how missing observations are handled, and which comparisons are intended. Prespecification can help distinguish planned analyses from analyses selected after outcomes are known. The registry record lists 0 analyses and does not report a statistical analysis plan, interim analyses, or a sample-size justification. It is therefore not possible to determine from the record which inferential methods were planned or whether any analyses changed over time.

The posted sample-size illustrations use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. These are planning illustrations, not the trial’s own design justification or observed power. The study itself is single group, so an equal-allocation, two-arm illustration should not be mistaken for the design actually used. Sample-size planning calculations describe hypothetical future designs under assumptions; they do not quantify the probability that this completed study detected an effect.

Why is over-dispersion relevant in general?

General explanation: Over-dispersion occurs when count data vary more than a statistical model assumes. If a model does not account for that extra variability, standard errors may be too small and confidence intervals too narrow. The registry record does not report a count model, an over-dispersion assessment, or an analysis of event episode counts. Since the primary endpoint is expressed as participants with events, the posted information does not establish that an event-count model was used or needed.

These methods concepts clarify what the registry information can and cannot support. The reported counts can be read descriptively. More detailed conclusions would require analysis definitions and results that are not reported in 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("Oral Miglustat")
n      <- c(6)
events <- c(6)
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  Oral Miglustat  6  6  100.0  54.1  100.0  61.0  100.0  59.0  99.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists several secondary outcomes in addition to the primary safety endpoint. They include pharmacokinetic measures—Cmax, Tmax, area under the curve, and half-life—and clinical outcomes based on Unified Batten Disease Rating Scale subscores and seizure frequency. The record lists 7 outcome measures, but it does not report numerical results for these secondary outcomes.

When a study evaluates multiple outcomes, the chance of at least one apparently noteworthy result can increase if many comparisons are tested without adjustment. General explanation: multiplicity methods can control or describe that issue by specifying which outcomes are primary, how comparisons are grouped, and whether significance thresholds or confidence intervals are adjusted. The registry record does not report a multiplicity plan, so it is not possible to determine whether or how multiple outcomes were handled.

Missing-data procedures are also not reported in the registry record. The record does not explain how missed visits, incomplete follow-up, withdrawal, or unavailable endpoint measurements were handled, nor does it state which participants were included in each analysis. Analysis populations, such as definitions based on treatment received or protocol adherence, are not reported in the registry record.

The registry lists 0 analyses. This indicates that analyses are not listed in the record; it does not establish whether analyses were conducted outside the registry. Without a reported analysis plan, outcome-level results, missing-data rules, and analysis populations, the posted information cannot show how complete the analyzed data were or whether the reported counts reflect a prespecified analysis. These gaps constrain interpretation of both safety and the secondary outcomes.

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: dysphagia (16.7%), medical device site cellulitis (16.7%).

The Oral Miglustat adverse-event figures list 1 participant with a serious adverse event, 6 participants with other adverse events, and 0 deaths. The registry lists Dysphagia and Medical device site cellulitis as serious-event terms, each at 16.7%. These are descriptive figures from the posted record, not comparisons against a control group.

A serious adverse event is a category of event; it is not synonymous with an event that is necessarily caused by the intervention. The registry record does not provide a causal assessment for the listed terms. It also does not report the event narratives, timing, duration, recurrence, or outcome needed to characterize each case in greater detail. The term percentages should not be used to infer whether the listed terms occurred in the same participant or to count total event episodes.

The endpoint is framed as a count of participants, so the figures concern people with events rather than the total number of episodes. The record does not explain how the serious-event terms relate to the count of participants with serious events. These limitations make the counts useful as a concise description of what is posted, but insufficient as a complete safety profile or a causal comparison.

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

The registry record documents a completed, open-label, single-group study of oral miglustat in people with CLN3 disease aged 17 years and older. It identifies safety, pharmacokinetics, and efficacy as study aims and reports participant counts for adverse-event categories. The primary endpoint is a participant count for treatment-emergent adverse events over 78 weeks. The posted adverse-event figures list 1 participant with a serious adverse event, 6 with other adverse events, and 0 deaths.

These registry entries do not establish that miglustat caused or prevented any event. Without a comparator, the study does not estimate how the same outcomes would have differed under another treatment or without treatment. The open-label design also means the record does not describe masked assessment. As a general statistical principle, descriptive observations from a small uncontrolled group are limited in precision and cannot by themselves isolate an intervention effect.

The study also lists pharmacokinetic and clinical efficacy outcomes, including scale subscores and seizure frequency. Numerical results for these outcomes are not reported in the registry record. The record therefore does not provide an efficacy estimate, a comparison, or a reported uncertainty interval for those outcomes. The posted adverse-event counts should not be treated as evidence for or against clinical efficacy.

The record does not report a sample-size justification, analysis populations, missing-data methods, multiplicity procedures, or a statistical analysis plan. Those omissions leave important questions about the intended analysis unanswered. Sample-size illustrations based on hypothetical assumptions are planning aids, not evidence of observed power and not a replacement for results from the study.

The defensible interpretation is narrow: the registry reports a small single-group experience and selected adverse-event counts, but does not provide enough comparative or analytic information to quantify treatment effects. It is not a basis for a definitive causal conclusion about safety or efficacy.

14. Why This Trial Matters Statistically

This study is statistically instructive because it brings together a small enrollment, an open-label design, and a single treatment group. Those features make careful separation of description from comparison especially important. Counts from participants who received miglustat can describe what was recorded in that group, but cannot show what the same participants would have experienced under a different condition.

The endpoint also illustrates why the unit of analysis matters. The primary outcome is titled as a number of treatment-emergent adverse events, while the record specifies participants as the unit and a count of participants as the parameter. A participant count and an episode count answer different questions. Readers should not interpret a count of affected participants as the number of event episodes or as a measure of duration.

Timeframes need similar care. The primary endpoint is listed at 78 weeks, while the described study period is 104 weeks. The record does not explain that difference. This makes it important to keep the endpoint timeframe distinct from the broader study duration rather than assume that one describes the other.

Finally, the registry lists secondary pharmacokinetic and efficacy outcomes but does not report their numerical results or analyses. The absence of an analysis plan, missing-data information, and multiplicity details further limits statistical interpretation. These are not merely technical omissions: they affect which conclusions can be supported and how precisely they can be stated. The record is informative about the design and selected safety observations, while leaving comparative and efficacy questions unresolved.

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 most important limitation is the absence of a comparator. The study is listed as single group, with no allocation and no masking. Therefore, the posted counts do not estimate a difference between miglustat and a control condition, and observed events cannot be attributed to treatment from the record alone.

Enrollment is listed as 6, and the brief summary describes approximately 6 subjects. This is a limited basis for characterizing uncommon or variable events. The registry record does not report a sample-size justification, so it does not explain the intended precision or the rationale for the enrollment target. The planning illustrations use assumptions for a hypothetical two-arm comparison and should not be confused with the study’s actual single-group design.

The timeframe for the primary endpoint is 78 weeks, while the study period is described as 104 weeks. The record does not explain how these timeframes relate. It also does not report detailed event-level data, missing-data methods, analysis populations, or a statistical analysis plan. As a result, it is not possible to determine how incomplete follow-up or repeated events were treated in analysis.

The record lists efficacy and pharmacokinetic outcomes but does not report their numerical results. It also does not report multiplicity procedures or confidence intervals. These limitations prevent assessment of the precision of outcome estimates and make it impossible to evaluate comparative efficacy from the registry information. The adverse-event terms and counts remain descriptive rather than a complete account of safety or treatment effect.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-label Safety, Pharmacokinetic, and Efficacy Study of Miglustat for the Treatment of Subjects With Batten Ceroid Lipofuscinosis, Neuronal 3 (CLN3) Disease — NCT05174039.
• Registry record last updated 2025-09-09; status last verified 2025-07.
• Results first posted 2025-09-09.
• 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 record describes a completed phase 1 and phase 2, open-label, single-group study of oral miglustat in people aged 17 years and older with CLN3 disease. Enrollment is listed as 6, and the brief summary describes approximately 6 subjects at 2 centers. The study period is described as 104 weeks; the primary safety endpoint has a 78-week timeframe.

The primary outcome is the number of participants with treatment-emergent adverse events. Posted adverse-event figures list 1 participant with a serious adverse event, 6 with other adverse events, and 0 deaths. Dysphagia and Medical device site cellulitis are listed as serious-event terms, each at 16.7%.

Pharmacokinetic measures and clinical efficacy outcomes are listed, but their numerical results are not reported in the registry record. No comparator, statistical analysis plan, missing-data procedures, or multiplicity plan is reported. The available figures support a descriptive account of the recorded safety categories, not a causal or comparative conclusion.