A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease (NCT04701411), a na phase 3 study. The primary outcome is Percentage of Participants Who Achieved Combined Remission.

2. Clinical Question

3. Trial Design

This was a Phase 3, open-label, multicenter, single-group study of darvadstrocel for complex perianal fistulas in pediatric participants with Crohn's disease. The registry records allocation as NA and masking as NONE. No randomized or concurrent comparator is registered, so the design is intended to describe outcomes among participants receiving the study intervention rather than estimate a treatment contrast between assigned groups. The registry lists enrollment as 7 and status as terminated. The reason for termination is not reported in the registry record.

The registered treatment sequence included fistula preparation surgery 2 to 3 weeks before darvadstrocel administration. That procedure was described as cleaning the fistula and draining any abscesses. On Day 0, the fistula was cleaned and darvadstrocel was administered as a perilesional injection under anesthetic. The arm description specifies a 24 milliliters (mL) suspension of 120 million cells, given once. The registry does not report how many of the enrolled participants ultimately received the injection.

The primary endpoint was assessed at Week 24. The study description also includes extended follow-up for a total of up to 52 weeks, with regular clinic visits to examine the fistula and record side effects. An MRI was planned at a clinic visit about 24 weeks after treatment. The registry lists secondary outcomes covering clinical remission and response, time to those outcomes, relapse among participants with combined remission at Week 24, and adverse events. These registered outcomes indicate the intended scope of follow-up, but do not provide their results.

The planned clinical procedures and follow-up should not be mistaken for evidence that all participants completed them. Actual treatment receipt, follow-up completion, and reasons for missing assessments are not reported in the registry record. Since the study was terminated and enrollment was 7, interpretation also depends on the available outcome data, which are not reported for the primary endpoint.

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 with complex perianal fistula due to Crohn's Disease (CD) participated in this study to receive darvadstrocel (Cx601). The study was terminated early based on the sponsor's decision and did not meet the planned enrollment number. All enrolled participants completed all the study assessments.

Overall Study

Analysis population for the primary outcome, as defined in the registry: Intent-to-treat (ITT) analysis set included all participants who underwent the fistula preparation procedure regardless of being treated or not.

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: Safety analysis set included all participants who received the study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved Combined Remission, measured over Week 24.

The primary endpoint is the percentage of participants who achieved combined remission at Week 24. The definition requires closure of all treated external openings that were draining at baseline despite gentle finger compression, and absence of abscesses greater than 2 centimeters in at least 2 dimensions, confirmed by central magnetic resonance imaging (MRI). A participant must satisfy both parts of the definition to meet the combined endpoint. This is more specific than counting improvement in only one opening or relying on symptoms alone.

Combining clinical examination with MRI provides complementary information: examination assesses whether draining external openings have closed, while imaging is used to assess abscesses in the treated perianal fistula. Central MRI assessment is part of the registered definition. These features make the endpoint a defined measure of fistula status at a specified follow-up time, rather than a broad judgment of overall health or a measure of change from baseline.

The analysis population is described as the intent-to-treat (ITT) set, including all participants who underwent the fistula preparation procedure regardless of whether they were treated. Although the endpoint title refers to a percentage, the registry lists the parameter as NUMBER and the dispersion as a 95% confidence interval. The primary estimate, its denominator, and its confidence interval are not reported in the registry record. The endpoint definition can therefore be explained, but the observed frequency of combined remission cannot be stated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What the endpoint percentage represents. In general, a percentage endpoint describes the share of the defined analysis population meeting a stated outcome definition at a specified time. For this trial, the outcome is combined remission at Week 24, and the registry identifies the ITT analysis set as participants who underwent fistula preparation, whether treated or not. The actual numerator, denominator, and percentage are not reported in the registry record, so no observed estimate can be interpreted. The endpoint label alone does not reveal how many participants met the criteria.

Why the definition matters. In general, a composite or combined endpoint requires more than one condition to be met. Here, all treated external openings that were draining at baseline despite gentle finger compression must be closed, and there must be no abscess greater than 2 centimeters in at least 2 dimensions, confirmed through central MRI assessment. A participant who meets only one part would not meet the registered combined definition. This creates a clear rule for classifying the outcome, but it also means the overall percentage depends on both clinical examination and imaging findings.

What a confidence interval conveys. In general, a confidence interval expresses uncertainty around an estimate, reflecting that an estimate from a study sample may differ from the underlying value in a broader population. A narrower interval indicates greater precision under the method's assumptions; a wider interval indicates more uncertainty. The primary endpoint lists a 95% confidence interval as its dispersion measure, but neither the interval nor the estimate is reported in the registry record. Precision therefore cannot be judged. With enrollment of 7, any interval would need to be interpreted in light of the small study size, but its actual width cannot be inferred without the result.

What the analysis population means. In general, an ITT population is intended to preserve the group defined for analysis rather than exclude participants based on whether they received the intervention or completed follow-up. The registered definition includes those who underwent fistula preparation regardless of treatment receipt. The record does not report how many participants met that population definition, how many were treated, or how missing Week 24 assessments were handled. Therefore, it is not possible to determine from the registry record whether the reported endpoint, if available elsewhere, follows this definition in practice.

Single-group evidence and comparison. In general, a control group helps distinguish changes associated with an intervention from changes that might occur for other reasons. This study has a single-group model, no masking, and no registered comparator. As a result, a remission estimate would be descriptive of the observed participants and would not supply a randomized contrast. The registry records allocation as NA; this does not mean that participants were randomized. The study design does not support a like-for-like control comparison.

Multiple outcomes and analysis choices. In general, studies that assess many outcomes face a multiplicity issue: examining several results can increase the chance that an apparently notable finding arises by chance, particularly when many tests are conducted. The registry lists 11 outcome measures and 0 analyses. It does not report a multiplicity adjustment, a hierarchy of testing, or a prespecified statistical analysis plan. Whether any adjustment was planned or conducted is not reported in the registry record. The list of outcomes by itself does not establish which outcomes were formally tested or how results should be prioritized.

Over-dispersion and count outcomes. In general, over-dispersion occurs when variability in count data exceeds what a simple statistical model assumes. It can make standard errors too small if the model does not account for the extra variation. The primary endpoint is a percentage based on a binary classification, not a count-rate outcome. The registry record does not specify a model for the primary endpoint, so a particular over-dispersion correction or other model choice cannot be attributed to this trial.

Planning illustrations versus observed power. In general, sample-size planning illustrations describe how many participants per arm might be needed under chosen assumptions to detect an effect; they do not indicate the probability that a completed study has demonstrated an effect. The registry's planning assumptions describe two-sided significance level 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. The registry also distinguishes total events for time-to-event illustrations from participants per arm for other illustrations. These assumptions are a planning framework, not the actual design of this single-group trial. Any sample-size illustration is not observed power, and no trial-specific sample-size justification is reported in the registry record.

Interim analyses and stopping. In general, interim analyses are planned looks at accumulating data before the end of follow-up and can affect statistical interpretation if they guide early stopping or decision-making. The registry status is terminated, but interim analyses and the reason for termination are not reported in the registry record. Termination status alone does not establish that an interim analysis occurred or that it was driven by efficacy, safety, recruitment, or another consideration.

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("Darvadstrocel")
n      <- c(7)
events <- c(3)
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  Darvadstrocel  7  3  42.9  9.9  81.6  15.8  75.0  15.7  75.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 11 outcome measures, including the primary combined remission endpoint, several clinical remission and response outcomes, time-to-event outcomes, relapse, and adverse event measures. It records 0 analyses. A list of outcomes does not indicate how many statistical tests were conducted, which outcomes were treated as confirmatory, or whether a multiplicity procedure was used. The statistical plan, testing hierarchy, and any adjustment for multiple comparisons are not reported in the registry record. Accordingly, the evidence available in the record does not support ranking reported findings by statistical priority.

Missing-data handling is also not reported in the registry record. This matters because the primary endpoint requires both a clinical assessment and central MRI information at Week 24. The record does not state how participants without an assessment were classified, whether missing MRI or clinical data were imputed, or whether sensitivity analyses were conducted. Nor does it report how many participants completed the Week 24 assessment or the extended follow-up. The registered ITT population includes participants who underwent fistula preparation regardless of whether they were treated, but the record does not give the resulting analysis-set size or explain how this definition was applied when data were unavailable.

The trial's status is terminated, but the record does not report the termination reason, any interim analysis, or a statistical stopping rule. A protocol-specific rationale for the sample size is not reported in the registry record. The planning illustrations use assumptions of a two-sided significance level 0.05, equal allocation between two arms, and a normal approximation; those assumptions do not describe this single-group study's actual design. They should not be interpreted as observed power or as a substitute for missing information about analysis populations, missing data, or multiplicity.

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: anal abscess (14.3%), proctalgia (14.3%).

The registry lists at least one treatment-emergent serious adverse event for 2 of 7 participants in the darvadstrocel group. It lists at least one other treatment-emergent adverse event for 6 of 7 participants, and deaths as 0. These are participant counts, not a comparison between treatment groups. No control group is registered, so the counts do not indicate how event occurrence differed from an untreated or alternative-treatment group.

Among the listed serious adverse event terms, anal abscess and proctalgia are each recorded at 14.3%. These term percentages should be read as reported; the record does not give further detail about event timing, recurrence, severity beyond the serious-event classification, or individual participant overlap. A participant may have more than one event, so term-level information should not automatically be treated as a count of distinct participants.

Adverse event listings describe events recorded during the study and do not, by themselves, establish that darvadstrocel caused them. The registry record does not report comparative safety estimates or a causal attribution analysis. Given the single-group design and enrollment of 7, the safety figures are descriptive observations from a small study population. They cannot establish how common the events would be in a broader population or how they compare with another treatment.

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

The registry record establishes what the investigators set out to assess: combined remission at Week 24 after darvadstrocel treatment in children and teenagers with Crohn's disease and complex perianal fistulas. It defines remission using closure of all treated external openings draining at baseline despite gentle finger compression and absence of abscesses greater than 2 centimeters in at least 2 dimensions on central MRI assessment. It also describes a regimen involving fistula preparation followed by a single perilesional injection, with follow-up extending for up to 52 weeks.

However, the primary endpoint result and its 95% confidence interval are not reported in the registry record. Without those values, the proportion meeting the combined remission definition and the precision of that estimate cannot be described. The record also does not report the number treated, the number with an evaluable Week 24 outcome, or how missing assessments were handled. Consequently, the endpoint definition and trial procedures should not be mistaken for evidence that the endpoint was achieved.

Even if an observed remission result were available, the single-group, open-label design would not provide a randomized comparison. It could describe the outcomes recorded among study participants, but would not establish what would have happened to comparable participants under another treatment or without darvadstrocel. The preceding fistula preparation and other aspects of care are part of the treatment context and cannot be separated from the injection's contribution through this design alone.

The status is terminated, with enrollment of 7. The termination reason is not reported in the registry record, so the status cannot be interpreted as evidence for or against efficacy or safety. Safety records list serious and other treatment-emergent adverse events, as well as 0 deaths, but those observations are descriptive and do not show causation or comparative risk. The record therefore supports an account of the study question, registered methods, and limited safety counts, but not a conclusion about treatment benefit or lack of benefit.

14. Why This Trial Matters Statistically

This study is statistically notable for asking a clearly defined clinical question in a population that the registry identifies as children and teenagers with Crohn's disease and complex perianal fistulas. The primary outcome combines clinical examination with central MRI assessment and fixes the assessment time at Week 24. A precise outcome definition matters because it establishes what counts as remission before interpreting any observed percentage. Here, meeting the endpoint requires both closure of the draining treated openings and absence of the specified abscess finding.

The registry also makes the limits of inference especially important. This is a Phase 3 study, but its design is single-group, open-label, and without a registered comparator. A study label or phase does not replace the information posted by the design: a single-group estimate can describe observed participants but cannot provide a randomized treatment contrast. Enrollment was 7, and the study is terminated. Those details emphasize the importance of transparent outcome counts, uncertainty estimates, and reasons for missing assessment, none of which are reported for the primary endpoint in the registry record.

The endpoint is clinically specific, yet its result and confidence interval are absent from the registry record. This illustrates a distinction between an endpoint being registered and evidence about its outcome being available. Registration establishes the planned question and definition; interpretation requires the actual result, analysis population, and uncertainty. The registry lists 11 outcome measures and 0 analyses, while details about multiplicity and missing-data handling are not reported in the registry record. This makes it difficult to evaluate how different outcome findings, if any, were analyzed and prioritized.

Finally, safety observations should be kept in their proper statistical context. The reported counts describe events among participants in a small, uncontrolled group and cannot establish comparative risk or causation. The study therefore matters statistically not because the registry record settles the treatment question, but because it shows why design, outcome reporting, uncertainty, and analysis transparency are essential to interpreting a clinical trial.

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 for interpreting efficacy is that the primary endpoint result and 95% confidence interval are not reported in the registry record. Although the endpoint definition and assessment time are specified, the observed percentage cannot be stated. The record also does not report the endpoint numerator or denominator, how many participants underwent the preparation procedure, or how many received darvadstrocel. This prevents assessment of the completeness of the primary analysis.

Enrollment was 7, and the trial was terminated. The registry does not report why it was terminated, how many participants completed follow-up, or whether Week 24 assessments were available for all participants. Since the endpoint depends on both clinical findings and MRI, absent information about missing assessments is particularly relevant. Missing-data methods, sensitivity analyses, and the statistical analysis plan are not reported in the registry record.

The design is single-group and open-label, with no registered comparator. An outcome in this group cannot distinguish treatment-associated change from the contribution of fistula preparation, other care, the natural course of disease, or influences on open-label assessment. Central MRI assessment is part of the endpoint definition, but the registry does not report additional safeguards for the clinical examination. The record also does not provide participant characteristics that would help describe the enrolled group or assess how representative it may be.

Although the registry lists secondary outcomes and adverse event counts, it does not report the listed efficacy results or analysis details. The reason for termination, interim analyses, multiplicity handling, and the trial's own sample-size justification are not reported in the registry record. Safety counts are descriptive, with no comparator for assessing relative event occurrence. These limitations constrain both the strength and scope of any interpretation based on the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Darvadstrocel for Treating Complex Perianal Fistulas in Children and Teenagers With Crohn's Disease — NCT04701411.
• Registry record last updated 2025-11-13; status last verified 2025-11.
• Results first posted 2025-10-06.
• 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 record describes a Phase 3, open-label, multicenter, single-group study of darvadstrocel for complex perianal fistulas in children and teenagers with Crohn's disease. Enrollment was 7, and the study status is terminated. Participants were described as receiving a single perilesional injection of 24 milliliters (mL) containing 120 million cells on Day 0, following fistula preparation.

The primary endpoint was combined remission at Week 24, defined using closure of draining external openings and central MRI assessment for abscesses greater than 2 centimeters in at least 2 dimensions. The primary result and its 95% confidence interval are not reported in the registry record. The reason for termination, missing-data methods, and statistical analysis plan are also not reported.

Safety information lists at least one serious adverse event for 2 of 7 participants, at least one other treatment-emergent adverse event for 6 of 7, and 0 deaths. These are descriptive findings without a registered control group.