Assessment of KAN-101 in Celiac Disease (ACeD): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Assessment of KAN-101 in Celiac Disease (ACeD) (NCT04248855), a randomized phase 1 study. The primary outcome is Incidence and Severity of Treatment-emergent Adverse Events (TEAEs).

2. Clinical Question

3. Trial Design

This completed Phase 1 study evaluated KAN-101 in patients with celiac disease. The registry describes a randomized, double-masked, sequential design and reports enrollment of 41. The study began on 2020-01-21 and reached primary completion on 2021-10-08. The record identifies Kanyos Bio, Inc., a wholly-owned subsidiary of Anokion SA, as sponsor.

The study had two parts. Part A was a first-in-human single-dose study: participants in the single ascending dose (SAD) cohorts received one dose of KAN-101. The cohort descriptions list KAN-101 Dose A, Dose B, Dose C, and Dose D. The posted adverse-event group labels also include SAD dose levels of 0.15mg/kg, 0.3mg/kg, 0.6mg/kg, 1.2mg/kg, and 1.5mg/kg. These are cohort descriptions, not a basis for assuming that every cohort had the same size or that doses were compared through a formal statistical test.

Part B was a multiple-dose study. Participants in the multiple ascending dose (MAD) cohorts were randomized to receive three doses of KAN-101 or placebo. The registry lists MAD cohorts at 0.15mg/kg, 0.3mg/kg, and 0.6mg/kg, as well as a MAD placebo group. It does not report the allocation ratio or further details of the randomization procedure.

Randomization and double masking are design features, but the record does not establish what procedures were used to preserve masking, how the sequential cohort progression was governed, or whether dose escalation depended on predefined review rules. Those details are not reported in the registry record. The record also does not report a sample-size justification. The study's stated purpose and endpoint are safety and tolerability; the design should not be read as a definitive efficacy comparison.

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.

Only the first 6 of 9 groups are shown.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All patients who received any amount of study drug with treatment group based on the dose level received.

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.

Only the first 6 of 10 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Incidence and Severity of Treatment-emergent Adverse Events (TEAEs), measured over Up to 28 Days.

The primary endpoint is the incidence and severity of treatment-emergent adverse events (TEAEs), assessed using the Common Terminology Criteria for Adverse Events (CTCAE) v5.0 or higher. Its timeframe is up to 28 Days. The endpoint population is all patients who received any amount of study drug, with treatment group assigned according to the dose level received.

Adverse-event endpoints are used in safety studies to describe the kinds of unwanted medical events that occur after treatment begins, how often participants are affected, and how severe the events are judged to be under the stated grading system. Counting participants with events gives a participant-level view: it is distinct from counting every event, because one participant may experience more than one event. Severity grading adds information beyond whether an event occurred, although the posted cohort counts do not provide a complete severity breakdown.

The registry record lists the endpoint title and assessment approach, but the posted results available in the record do not include a complete set of endpoint estimates by severity category or a statistical comparison. The separate adverse-event listing reports serious-event counts and counts for other adverse events by group. Those counts are useful descriptive safety information, but they should not be treated as a complete tabulation of the primary endpoint unless the registry record explicitly provides that detail.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record describes a randomized, double-masked, sequential Phase 1 study, but it does not report a detailed statistical analysis plan. The endpoint and cohort counts can still be read using general statistical principles. These principles explain what the reported numbers can describe and what they cannot establish.

What does a participant count represent?

The adverse-event listing gives the number of participants at risk and the number affected in each group. A participant count is a measure of how many people had at least one event in the category being reported. It does not count the total number of individual episodes if a participant experienced repeated events. For this reason, participant counts and event counts answer different questions.

In a safety study, participant counts are useful because they show how many people experienced an event. However, the interpretation depends on the event definition, the observation period, and which participants are included. The primary endpoint specifies treatment-emergent adverse events assessed through up to 28 Days, while the adverse-event listing separates serious events from other adverse events. The record does not provide enough detail in the posted counts to reconstruct a full event-level or severity-level profile.

Why are the cohort counts descriptive?

A randomized comparison is most informative when the groups being compared are defined by the study design and the analysis follows a stated plan. Here, the registry describes single-dose KAN-101 cohorts and multiple-dose cohorts that include placebo. The SAD groups do not have a listed placebo group, so their counts describe events observed after KAN-101 rather than a controlled contrast. The MAD placebo group offers a comparator within that part, but the record does not report a formal statistical comparison between it and each dose group.

Observed counts can differ for many reasons, including chance variation, differences in group size, and differences in participants' event histories. Randomization is intended to support fair comparisons between assigned groups, but a reader still needs the relevant analysis, uncertainty estimates, and information about the analysis population to interpret a contrast. The registry record does not report those elements for the primary endpoint. The fact that the trial is described as randomized does not itself turn every comparison of cohort counts into a planned inferential analysis.

What would a confidence interval add?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a specified statistical model. It can show whether the data are compatible with a range of values, rather than presenting only a point estimate. For event counts or event proportions, uncertainty is important because small cohorts can yield unstable estimates. The posted serious-event and other-event counts do not include confidence intervals. No interval should be inferred from the counts without specifying a method and performing an analysis.

A confidence interval would not remove limitations in design or measurement. It would quantify statistical uncertainty under the chosen method, not address possible missing observations, differences in follow-up, or limits in how events were collected. The record does not state whether any participants had incomplete safety follow-up or how such cases were handled.

How should the zero serious-event counts be read?

In general, observing no events in a group is not equivalent to proving that an event cannot occur. A zero count is an observation in the participants and follow-up represented by the record. Its interpretation depends on how many people were observed, the length and completeness of observation, and the way events were classified. The listed groups show zero serious adverse events and zero deaths, but the record does not provide confidence intervals or a formal analysis of the serious-event risk.

The endpoint is assessed by CTCAE v5.0 or higher. Grading systems standardize the description of severity, which can improve consistency in safety reporting. Yet the posted adverse-event figures do not give a full distribution by CTCAE grade. The title of the endpoint refers to incidence and severity; the available group counts alone cannot show how severity was distributed among participants with events.

What can be concluded from the analysis information?

The registry record lists three outcome measures and no analyses for those measures. It therefore does not report a model, hypothesis test, confidence interval, covariate adjustment, or multiplicity procedure for the primary endpoint. The record does not report whether interim analyses were planned or conducted. None of these details should be inferred from the trial's Phase 1 status, masking, or randomization.

The record describes a sample-size planning illustration based on an observed effect, with stated assumptions including a two-sided significance level of 0.05, equal allocation, and a normal approximation. It also indicates that the illustration is not the trial's own design. The primary outcome is flagged as having several categories or time points and not being reduced to one comparison. Consequently, the illustration is not evidence that the trial was designed to detect a particular treatment effect, and it is not observed power. The registry record does not report the trial's sample-size justification.

In general, statistical power is a design concept concerning the chance that a specified analysis would detect a specified effect under stated assumptions. It is not a measure of whether a completed study has demonstrated an effect. For this trial, no power calculation from the observed results should be used to characterize the strength of evidence. The posted counts and the absence of reported analyses support a cautious descriptive reading rather than a claim of statistical equivalence, difference, or absence of risk.

10. Multiplicity, Missing Data and Analysis Populations

The primary endpoint concerns both incidence and severity, and the registry indicates that the outcome has several categories or time points rather than a single comparison. The record lists three outcome measures and no analyses for those measures. It does not report a prespecified strategy for handling multiple comparisons, categories, or time points. Without that information, the reader cannot determine whether any specific comparison was primary for statistical testing or how the risk of false-positive findings was addressed.

Missing-data methods are not reported in the registry record. The record does not state whether participants missed assessments, had incomplete follow-up, withdrew, or had safety observations that were unavailable. It also does not explain how incomplete observations would be handled in the endpoint analysis. The reported at-risk counts indicate group denominators for the posted adverse-event listing, but do not establish that all participants had complete observation through the stated timeframe.

The primary endpoint population is described as patients who received any amount of study drug, grouped by dose level received. That is a treated-population definition. The registry record does not report a separate intention-to-treat analysis population, a per-protocol population, or rules for participants who did not complete assigned treatment. It also does not describe how deviations from randomized assignment, if any, were handled.

These omissions limit interpretation of both the endpoint and comparisons between groups. The record does not report whether multiplicity adjustment, imputation, sensitivity analyses, or interim analyses were used. Their absence from the registry record should not be taken to mean that they were or were not conducted; the relevant methods are simply not reported there.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The serious adverse-event listing reports 0 affected participants in each of the listed groups, and the death count is 0 in each group. These are observed counts, not proof that serious events or deaths are impossible. Group sizes are small, and the registry record does not provide confidence intervals for the serious-event counts or a formal comparison across groups.

The listing separately reports participants affected by other adverse events. The SAD group counts are 4 of 4 at 0.15mg/kg, 3 of 3 at 0.3mg/kg, 2 of 3 at 0.6mg/kg, 3 of 3 at 1.2mg/kg, and 1 of 1 at 1.5mg/kg. The MAD group counts are 6 of 6 at 0.15mg/kg, 5 of 7 at 0.3mg/kg, 7 of 8 at 0.6mg/kg, and 4 of 6 for placebo. These counts should be understood as cohort descriptions, not as evidence of a statistically tested difference. The posted results do not provide a complete severity breakdown for these other events.

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

The registry record documents a completed Phase 1 safety study of KAN-101 in patients with celiac disease, with single-dose and multiple-dose cohorts. It reports no serious adverse events and no deaths in any listed group. It also reports participants with other adverse events in each listed group. Those observations describe the safety experience captured in the record for the participants and groups listed.

The counts do not establish that KAN-101 is safe or unsafe, and they do not show whether KAN-101 differs from placebo. The SAD cohorts have no listed placebo comparator, and the record does not report a formal analysis comparing the MAD dose groups with placebo. No inferential analyses are listed for the outcomes. Small group counts and the absence of reported uncertainty estimates make the precision of any comparative interpretation unclear.

The endpoint is broader than the serious-event count: it is defined as incidence and severity of treatment-emergent adverse events assessed by CTCAE v5.0 or higher. The posted group listing does not provide a complete severity profile for all events, so the serious-event counts alone do not summarize every aspect of that endpoint. The record also does not report detailed missing-data handling or completeness of follow-up.

These results should be interpreted within the scope of an early-phase, safety-focused study. They do not answer questions about clinical benefit, long-term outcomes, or safety in populations beyond the patients studied. Such conclusions are not reported by the registry record. The most defensible reading is that the record supplies descriptive adverse-event counts by dose group and placebo group, while leaving comparative effects and their precision unquantified.

13. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase clinical research: safety data are important, but cohorts may be small and organized around dose progression rather than a single large comparison. Counts can identify events observed during the study and help describe the experience in each cohort. They do not automatically provide precise estimates of event risk or a reliable ranking of doses.

The design combines single-dose KAN-101 cohorts with multiple-dose cohorts that include placebo. That distinction matters for interpretation. The single-dose counts are descriptive because the listed cohorts have no placebo group; the multiple-dose placebo group provides a comparator in that part, but the registry record does not report a formal statistical contrast. A reader should not treat raw differences in counts as equivalent to a randomized treatment-effect estimate.

The record also demonstrates why endpoint definitions and analysis details matter. The primary endpoint includes both incidence and severity, but the adverse-event listing reports counts for serious events and other events rather than a complete severity distribution. No analyses are listed for the outcome measures, and confidence intervals, missing-data methods, and multiplicity procedures are not reported. These gaps constrain what can be inferred, even when the observed counts are clear.

Statistically, the study is most informative as a description of adverse events observed in its listed cohorts. Its results also show why zero serious events should be read as an observation with uncertainty, rather than as evidence of zero risk. Keeping descriptive evidence separate from comparative or confirmatory evidence is essential when communicating safety results from a small Phase 1 study.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

The registry record gives limited detail on the statistical methods. It lists no analyses for the outcome measures and does not report confidence intervals, hypothesis tests, covariate adjustment, or a prespecified comparison for the primary safety endpoint. The method used to summarize severity is not fully represented in the posted cohort counts.

The available adverse-event groups are small, and the record does not provide uncertainty estimates for their counts. The zero serious-event counts and zero deaths therefore describe the listed observations, but do not quantify the range of plausible underlying risks. The counts for other adverse events are also sensitive to the experiences of individual participants in small cohorts.

The cohort structure limits direct comparisons. SAD cohorts received KAN-101, while placebo is listed among the MAD groups. The record does not report a formal comparison across these parts, nor does it provide details about the randomization procedure or allocation ratio. A randomized, double-masked designation alone does not establish how particular cohorts should be compared statistically.

Information about follow-up completeness, withdrawals, missing observations, and handling of incomplete data is not reported in the registry record. The record also does not provide a detailed account of adverse-event ascertainment beyond the stated CTCAE assessment. Finally, the trial is described as a safety study, and the posted results do not report evidence on clinical efficacy or long-term outcomes. These limitations narrow the conclusions to a descriptive account of the recorded adverse events.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Assessment of KAN-101 in Celiac Disease (ACeD) — NCT04248855.
• Registry record last updated 2024-08-06; status last verified 2024-08.
• Results first posted 2024-03-21.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT04248855 is a completed, randomized, double-masked, sequential Phase 1 study of KAN-101 in patients with celiac disease. The registry reports enrollment of 41 and describes a single-dose part and a multiple-dose part. In the latter, participants received three doses of KAN-101 or placebo.

The primary endpoint was incidence and severity of treatment-emergent adverse events, assessed using CTCAE v5.0 or higher through up to 28 Days. The adverse-event listing reports 0 serious adverse events and 0 deaths in each listed group, with separate counts for other adverse events. The registry record lists no outcome analyses and does not report confidence intervals, missing-data methods, or a formal comparison of treatment groups. The posted counts are therefore descriptive, and their comparative precision is not quantified.