A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula (NCT04118088), a na phase 4 study. The primary outcome is Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE).

2. Clinical Question

3. Trial Design

This was a Phase 4, single-group, open-label postauthorization safety study of darvadstrocel in adults with Crohn’s disease and complex perianal fistula. It enrolled 53 participants. The study is listed as terminated; the reason for termination is not reported in the registry record. Its listed start date is 2020-12-22, and its primary completion date is 2025-02-14.

Participants had previously received darvadstrocel and were given a single repeat dose. The intervention description specifies a 24 mL suspension of 120 million cells, at 5 million cells/mL, injected around the fistula. The brief summary describes 8 clinic visits, with the treatment administered at the third visit. Magnetic resonance imaging was to be performed several times during the study. Further details about visit timing and imaging procedures are not reported in the registry record.

The design has no randomized allocation, no masking, and no separate comparator arm. Consequently, the study can describe events observed among treated participants over follow-up, but it cannot provide a randomized estimate of how those events compare with outcomes under another treatment or no treatment. The registry names long-term safety as the main aim and also describes an interest in symptoms and fistula outcomes. Its listed secondary outcomes include combined remission, clinical remission, clinical response, relapse, time to relapse, new perianal abscess, and changes in selected Perianal Disease Activity Index items.

The registry record defines the safety population as enrolled participants who received darvadstrocel. It does not report eligibility criteria in detail, the reason the study was terminated, or the rationale for the planned enrollment.

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 a diagnosis of Crohn's Disease (CD) and complex perianal fistula were enrolled in this study to receive a single repeated administration of darvadstrocel (Alofisel). The study was terminated early based on the sponsor's decision.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: SAF consisted of all participants who were enrolled in the study and received treatment with darvadstrocel.

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 (SAF) consisted of all participants who were enrolled in the study and received treatment with darvadstrocel.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With at Least One Treatment-Emergent Adverse Event (TEAE), measured over From signing of informed consent form (ICF) up to 156 weeks post-repeat administration (the only administration in this study), up to approximately 164 weeks.

The primary endpoint is the percentage of participants with at least one treatment-emergent adverse event (TEAE). The registry defines an adverse event as an untoward medical occurrence in a participant given a medicinal product, whether or not it is considered causally related to treatment. A TEAE is an adverse event whose onset occurs after study drug is received. This definition concerns timing and does not, by itself, establish that treatment caused an event.

The endpoint is intended to describe how many treated participants experienced at least one qualifying event during the specified observation period. The record gives that period as beginning with informed consent and continuing through 156 weeks after the repeat administration, up to approximately 164 weeks. The measure is a participant-level percentage: a participant with multiple events still contributes as a participant with at least one event for this endpoint.

In general, a participant-level measure can provide a straightforward summary of how widespread an event was in the observed group. It does not convey the number of events per participant, their duration, or their severity unless those details are reported separately. Nor does the TEAE definition prove a causal relationship. The registry record does not report a numerical result for the primary endpoint, its uncertainty interval, or a statistical comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is the primary endpoint?

The primary endpoint is a binary participant-level outcome: each participant either had at least one TEAE during the defined observation period or did not. The intended summary is a percentage of participants. In general, binary outcomes are often described by the number of participants with the event and the number assessed, together with an uncertainty interval. The registry record identifies the endpoint and its definition, but does not report its numerical result or a confidence interval.

For a participant-level endpoint, the count of people with one or more events is not the same as a count of all event occurrences. A participant may experience more than one adverse event, while still contributing only once to the “at least one” endpoint. Event counts, event rates over time, severity, and relatedness can answer different questions. The posted safety summary separately lists serious and other adverse-event categories, but the registry record does not report enough detail to reconcile those summaries with the primary endpoint result.

How should a percentage be understood?

In general, a percentage of participants is a proportion: the event count is interpreted relative to the number of participants in the analysis population. The denominator matters because it indicates who was included and whether everyone in the intended population contributed to the measure. Here, the safety population is defined as participants enrolled and treated, and the adverse-event summary lists 53 at risk. A numerical primary-endpoint percentage, and details on any participants not included in a particular analysis, are not reported in the registry record.

In general, an uncertainty interval around a proportion helps distinguish a relatively precise estimate from one that remains uncertain. An interval is not a guarantee that the true value lies within it, and its interpretation depends on the statistical method and assumptions. No interval or method for estimating uncertainty for the primary endpoint is reported in the registry record, so precision cannot be assessed from that endpoint.

What can this design estimate?

A single-group study can summarize observed outcomes in the treated group. Without a concurrent control group, it cannot directly estimate a contrast between treatment and control. In general, before-and-after or single-group observations may reflect the condition’s course, other care, participant selection, or changes in observation as well as treatment. Those influences cannot be separated using a randomized comparison when no such comparison is part of the design.

The study is open-label, meaning masking is listed as none. In general, knowledge of treatment can influence subjective reporting, clinical assessment, decisions to investigate symptoms, and decisions to classify an event. This does not establish that any particular assessment was biased; it identifies a consideration when interpreting outcomes that can involve judgment. The registry record does not report additional procedures for limiting such influence.

How do follow-up and event timing matter?

The primary endpoint covers events beginning after study drug and follows participants through 156 weeks post-repeat administration, up to approximately 164 weeks from informed consent. In general, longer observation can capture events that arise later, but the opportunity to observe an event depends on how long each participant is followed and whether follow-up is complete. A percentage accumulated over a period is not the same as an event rate that accounts for differing follow-up time.

The registry record does not report participant-level follow-up duration, censoring rules, or methods for handling participants who stop attending visits. It also does not report whether time-to-event methods were applied to the secondary outcome “Time to Relapse.” Therefore, the listed outcome name alone does not establish how relapse timing was analyzed.

What do the sample-size illustrations mean?

Any sample-size figures presented as planning illustrations are calculations based on the observed effect, not the trial’s own design justification. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event outcomes, the illustration concerns a total number of events; for other outcomes, it concerns participants per arm.

These are general planning calculations, not observed power and not evidence that a study has or lacks a particular probability of detecting an effect. They do not turn this single-group study into a two-arm comparison, and they do not provide a result for an outcome. The registry record does not report a protocol-based sample-size justification. Since numerical analyses of the outcomes are not reported, a planning calculation cannot be interpreted as an estimate of treatment effect.

Were inferential methods reported?

The registry lists 11 outcome measures and 0 analyses. It does not report a statistical analysis plan, a model used for the primary endpoint, hypothesis tests, confidence intervals, or adjustment for covariates. Those details should not be inferred from the endpoint definition or from the study’s Phase 4 designation. In general, an analysis method needs to match the outcome, follow-up structure, and estimand; the registry record does not provide the information needed to evaluate such choices for this study.

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(53)
events <- c(35)
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  53  35  66.0  51.7  78.5  52.6  77.3  52.5  77.3

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 11 outcome measures overall, including a primary safety outcome and several secondary outcomes relating to remission, response, relapse, abscess, and symptom scores. It reports 0 analyses. Numerical results for these outcomes and a multiplicity strategy are not reported in the registry record.

In general, testing many outcomes can increase the chance of finding at least one apparently notable result by chance. A prespecified hierarchy, adjustment method, or clear distinction between confirmatory and exploratory outcomes can help readers interpret multiple tests. The record does not report whether such a plan was used, so no conclusion about multiplicity control is possible.

Missing-data methods are also not reported in the registry record. The definition of the safety population identifies enrolled participants who received treatment, but does not explain how missing visits, incomplete follow-up, or unavailable outcome measurements were handled. In general, missingness can affect a percentage if participants with unknown outcomes are excluded or treated in a particular way. Without the numbers assessed for each outcome and the handling rules, the effect of missing data cannot be evaluated.

The registry record does not report an analysis population for each secondary outcome, a method for handling participants who discontinue, or sensitivity analyses. These are distinct from the safety-population definition and should not be assumed from it.

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 (1.9%), cerebrovascular accident (1.9%), proctalgia (1.9%).

The registry’s adverse-event summary lists 53 participants at risk in the Darvadstrocel group. It lists 3 participants affected in the serious-event category, 20 in the other-event category, and 0 deaths. These categories are presented separately; the figures should not be added together or treated as mutually exclusive groups without information about overlap. The registry record does not report details that would establish whether participants could appear in both categories.

The listed top serious terms are Anal abscess, Cerebrovascular accident, and Proctalgia, each reported at 1.9%. These term-level percentages describe entries in the serious-event summary. They do not establish that an event was caused by darvadstrocel. In the registry’s definition, an adverse event need not be causally related to treatment, and a TEAE is defined by onset after study drug.

The serious-event count is not a substitute for the primary endpoint, which concerns the percentage of participants with at least one TEAE. A numerical result for that endpoint is not reported in the registry record. Details about event timing, recurrence, severity beyond the serious classification, relatedness, and follow-up completeness are also not reported, limiting what can be inferred from these summary figures.

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

The posted information establishes the study’s purpose, design, intervention, follow-up window, and the types of outcomes it intended to assess. It also provides a limited adverse-event summary. The record lists 3 participants affected in the serious-event category and 20 in the other-event category among 53 at risk, with 0 deaths. Three serious-event terms are listed at 1.9% each. These figures describe the registry’s reported safety summaries; they do not show whether treatment caused an event.

The registry record does not report the numerical result for the primary endpoint, the percentage of participants with at least one TEAE. It also does not report numerical results for the listed remission, response, relapse, abscess, or symptom outcomes. Consequently, the intended efficacy-related questions cannot be answered from the posted outcome results. The fact that outcomes were named does not mean their results were observed, analyzed, or favorable.

The study has no randomized control group, so observed outcomes cannot be directly contrasted with a concurrent comparator. General statistical interpretation of a single-group result is descriptive: it characterizes participants in the study and does not establish what would have occurred under another treatment or without treatment. No treatment-effect conclusion follows from the design or the fact that participants received a repeat dose.

Precision is also unknown for the primary endpoint because an estimate and confidence interval are not reported. A sample-size planning illustration, if consulted, is not an observed treatment effect or observed power. The study’s terminated status does not explain why it ended; the reason is not reported in the registry record. Taken together, the available information supports a description of study conduct and limited safety counts, but not a complete statistical assessment of long-term safety or efficacy.

14. Why This Trial Matters Statistically

This trial is statistically notable because it asks a long-term safety question after repeat darvadstrocel administration in a postauthorization setting. Follow-up was planned through 156 weeks after the repeat administration, up to approximately 164 weeks from informed consent. Such a duration makes the distinction between a participant-level event percentage and an event rate over time especially relevant: a cumulative percentage does not account for differing time under observation unless the analysis specifically does so.

The study also illustrates the limits of interpreting safety results without a concurrent comparator. A single-group record can describe events among treated participants, but cannot determine how those events compare with an alternative group under the same observation conditions. The endpoint definition appropriately distinguishes an event occurring after treatment from an event caused by treatment; timing alone is not proof of causality.

Another statistical issue is the gap between outcomes planned and outcomes numerically reported. The registry lists safety as the primary question and multiple fistula-related secondary outcomes, but lists 0 analyses. Without outcome estimates, uncertainty intervals, and analysis details, readers cannot judge precision or evaluate the secondary clinical questions from the record.

Finally, the record shows why enrollment and adverse-event counts should not be mistaken for a full analysis. The 53 participants at risk and the listed safety counts provide limited descriptive information, but they do not replace the primary endpoint result or explain missing follow-up. The terminated status is relevant context, although its reason is not reported in the registry record. These distinctions help keep descriptive evidence separate from comparative or causal claims.

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 main limitation is the single-group design. Allocation is listed as not applicable, masking as none, and the study model as single group. There is no randomized comparator in the registry record, so observed events cannot be contrasted with outcomes under another treatment or no treatment. This restricts interpretation to description of the treated group and prevents a randomized estimate of comparative effect.

The primary endpoint result is not reported in the registry record, even though its definition and follow-up period are specified. The registry lists 0 analyses and does not report confidence intervals, hypothesis tests, or a statistical model. The secondary outcomes are named, but their numerical results are not reported. Thus, the outcome information is insufficient to assess the magnitude or precision of the primary endpoint or the listed secondary outcomes.

The safety summary provides limited counts and term-level percentages, but does not report event narratives, timing, recurrence, relatedness assessments, or participant-level overlap between categories. The record also does not report how incomplete follow-up or missing outcome data were handled, whether participants discontinued, or whether sensitivity analyses were performed.

The study is marked terminated, but the reason is not reported in the registry record. A protocol-based sample-size justification, detailed eligibility criteria, multiplicity plan, and full statistical analysis plan are also not reported. These omissions mean that the intended design rationale and the robustness of any outcome analysis cannot be evaluated from the registry information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of Darvadstrocel in Adults With Crohn's Disease and Complex Perianal Fistula — NCT04118088.
• Registry record last updated 2026-01-22; status last verified 2026-01.
• Results first posted 2026-01-22.
• 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

NCT04118088 is a Phase 4, single-group postauthorization safety study of repeat darvadstrocel in adults with Crohn’s disease and complex perianal fistula. The registry lists 53 participants, no masking, and a terminated status. The listed primary endpoint is the percentage with at least one TEAE over follow-up from informed consent through 156 weeks after repeat administration, up to approximately 164 weeks.

The intervention was a single repeat perilesional injection of 24 mL containing 120 million cells. The safety summary lists 3 participants affected in the serious-event category, 20 in the other-event category, and 0 deaths among 53 at risk. Three top serious-event terms are each listed at 1.9%. The primary endpoint and secondary outcome results are not reported in the registry record; the record lists 0 analyses.