Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis (NCT04130919), a randomized phase 2 study. The primary outcome is Percentage of Participants Who Achieved Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 10.

2. Clinical Question

The trial asked whether tilpisertib could achieve clinical remission in adults with moderately to severely active ulcerative colitis, compared with placebo. The primary assessment was at Week 10 and used remission defined by the modified Mayo Clinic Score (MCS). The randomized, blinded-treatment groups received tilpisertib 300 mg, tilpisertib 100 mg, or matching placebo.

This is a question about a defined clinical state at a specified assessment, not about change in an average score. The remission definition combines stool frequency, rectal bleeding, and endoscopic findings. As a result, a participant had to meet all of the stated component criteria to count as being in remission. The registry also listed endoscopic response, MCS response and remission, histologic remission, treatment-emergent adverse events, and laboratory abnormalities as secondary outcomes.

3. Trial Design

This was a Phase 2, randomized, double-blind, parallel-group, placebo-controlled study sponsored by Gilead Sciences. The registry lists 19 participants as enrolled. The primary completion date was 2021-02-25, and the study status is terminated. The reason for termination is not reported in the registry record.

The blinded-treatment phase included three randomized arms: tilpisertib 300 mg, tilpisertib 100 mg, and placebo. Participants were to receive their assigned blinded treatment for up to 10 weeks, with an efficacy assessment at Week 10. The arm descriptions state that participants who achieved MCS response would continue blinded treatment for up to 50 weeks. Participants who did not achieve MCS response could have the option to receive open-label tilpisertib 300 mg for up to 50 weeks.

The primary outcome population was the full analysis set: randomized participants who received at least 1 dose of study drug. The posted arm sizes for the primary outcome were 7 for tilpisertib 300 mg, 6 for tilpisertib 100 mg, and 6 for placebo. These are the denominators displayed for the primary outcome; they should not be confused with the broader enrollment figure or with the open-label safety groups.

Randomization and masking are design features intended to support fair comparisons and reduce the influence of expectations on treatment delivery or assessment. In general, random allocation helps balance measured and unmeasured participant characteristics across groups on average, while masking can limit bias in reporting and outcome assessment. These features do not remove uncertainty, particularly when the groups are small, and they do not substitute for reported outcome comparisons or uncertainty intervals.

The registry record does not report additional details about the randomization procedure, allocation concealment, or how masking was maintained. Nor does it report a reason for the terminated status or explain how termination affected planned follow-up. Those details cannot be inferred from the design labels or the arm descriptions.

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: 32 participants were screened.

Blinded Treatment Phase

Reasons for not completing this period:

Open-label Treatment Phase

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set included all randomized participants who received at least 1 dose of study drug.

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 at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved Clinical Remission Per Modified Mayo Clinic Score (MCS) at Week 10, measured over Week 10.

The primary endpoint was the percentage of participants achieving clinical remission per modified MCS at Week 10. The modified MCS combines subscores for endoscopy, rectal bleeding, stool frequency, and physician's global assessment (PGA). Each subscore ranges from 0 to 3, and the total ranges from 0 to 12, with higher scores indicating greater disease activity.

For the primary remission definition, participants had to have a stool-frequency subscore of at most 1 and not greater than baseline, a rectal-bleeding subscore of 0, and an endoscopic subscore of at most 1 at Week 10. The PGA contributes to the total MCS but is not among the component thresholds stated in this remission definition. The definition therefore identifies a specific combination of bowel symptoms and endoscopic findings rather than relying on a single score or symptom.

A percentage endpoint is used to describe how many participants in an arm meet the defined state at the assessment time. It is clinically interpretable as the proportion meeting a prespecified clinical criterion, but it does not show how close other participants came to that criterion or how individual scores changed. The registry lists the outcome unit as percentage of participants and the measure as a number. The posted Week 10 values were 0.0 in all three blinded-treatment arms.

The registry record does not report additional detail on how the component scores were assessed, who performed the assessments, or how missing component measurements were handled. Those matters can affect the interpretation of a composite remission endpoint and are not resolved by its definition alone.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary at the participant level: each participant either meets the Week 10 clinical-remission definition or does not. The arm-level summary is the percentage of participants meeting that definition. This makes the endpoint different from a continuous measure such as a mean score. A percentage describes the frequency of an event in an arm; by itself, it does not describe the magnitude of score changes among participants who did not meet remission criteria.

What does a percentage estimate?

In general, a sample percentage is an estimate of the event frequency in the population from which participants were drawn. Its precision depends on how many observations contribute and how common the event is. With a small number of participants, one participant's outcome can have a substantial influence on the displayed percentage. The registry lists 7 participants in the tilpisertib 300 mg arm, 6 in the tilpisertib 100 mg arm, and 6 in the placebo arm for the primary outcome. The observed endpoint value is 0.0 in each arm. These are descriptive results; they are not a measure of how certain the underlying population percentages are.

Why is a comparison not available?

A treatment comparison for a binary endpoint typically contrasts event percentages between arms, or uses another prespecified model to estimate a treatment effect. General approaches can also provide an interval estimate and a test of a null hypothesis. The registry record does not report such an estimate, interval, or test for this primary endpoint. It specifically indicates that values are missing or not estimable for a two-arm comparison of the binary percentage outcome. The zero event values should therefore not be turned into a comparative estimate by treating the arms as if they had a measurable difference in response.

In general, confidence intervals communicate uncertainty around an estimate by giving a range of values compatible with the data and method. A p-value, when reported, addresses the compatibility of data with a specified null model; it is not the probability that a treatment works or that the null hypothesis is true. Neither a confidence interval nor a p-value for the primary comparison is reported in the registry record. The absence of these statistics prevents a direct assessment of comparative precision or statistical evidence from the posted primary results.

How should the planning illustrations be understood?

Sample-size calculations are planning tools, not summaries of trial outcomes. The stated planning approach uses a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect defined as a stated fraction of the observed effect. The registry entries characterize these calculations as planning illustrations based on the observed effect, not as the trial's own design justification. For non-time-to-event outcomes, such illustrations refer to participants per arm. They should not be described as observed power or as evidence that the trial had a particular probability of detecting a treatment effect.

Because the primary two-arm comparison is not estimable, a planning illustration based on a primary observed effect cannot supply the missing comparative estimate. The trial's own sample-size justification is not reported in the registry record. The registry also does not report whether a prespecified target effect or other assumptions were used in the original design.

What can be inferred from the design labels?

Randomization, double masking, and a parallel-group structure describe how the study was organized. In general, randomization aims to reduce systematic differences between arms at allocation, and masking aims to limit bias in conduct and assessment. These design features do not guarantee balanced characteristics in a small study, and they do not fill gaps in outcome reporting. The registry record does not report the detailed randomization method, allocation concealment method, or masking procedures.

The listed analysis population consists of randomized participants who received at least 1 dose of study drug. This definition identifies who was intended to contribute to the primary endpoint, but it does not describe every analysis decision. The record does not report the analysis model, treatment of missing Week 10 data, handling of participants who discontinued, or sensitivity analyses. It also reports 0 analyses, so no analysis-specific estimates or methods are available to clarify these matters.

Why do safety and efficacy summaries differ?

Safety outcomes are often summarized as counts of participants experiencing an event within a defined exposure group, whereas the primary endpoint is the percentage achieving remission at a fixed assessment. General interpretation of safety counts requires attention to the group definition, the number at risk, exposure, and the event definition. The registry reports safety groups for both blinded and open-label treatment phases, and those groups are not interchangeable with the randomized primary-outcome arms. Open-label groups consist of participants entering later treatment based on their earlier course, so their counts should not be treated as randomized comparisons.

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("Tilpisertib 300 mg (Blinded Treatment Phase)", "Tilpisertib 100 mg (Blinded Treatment Phase)", "Placebo (Blinded Treatment Phase)")
n      <- c(7, 6, 6)
events <- c(0, 0, 0)
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  Tilpisertib 300 mg (Blinded Treatment Phase)  7  0  0.0  0.0  41.0  0.0  35.4  0.3  36.9
ARM  Tilpisertib 100 mg (Blinded Treatment Phase)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0
ARM  Placebo (Blinded Treatment Phase)  6  0  0.0  0.0  45.9  0.0  39.0  0.4  41.0

11. Multiplicity, Missing Data and Analysis Populations

The registry lists six secondary outcomes in addition to the primary clinical-remission endpoint. Multiple outcomes create a multiplicity issue: in general, the more hypotheses examined, the greater the chance that at least one result appears notable by chance if each is interpreted separately. Statistical plans may address this through a hierarchy, an adjustment, or a clearly defined exploratory interpretation. The registry record does not report a multiplicity strategy, a testing hierarchy, or which outcomes were intended to support confirmatory claims. The listed outcomes alone do not establish that they were all formally tested.

The record reports 0 analyses. It does not provide a statistical analysis plan, a description of the primary analysis model, or details about whether any interim analyses were planned or conducted. These details are not reported in the registry record. No assumption about testing order, interim monitoring, or error-rate control can be made from the available information.

Missing-data handling is also not reported in the registry record. For a Week 10 endpoint, incomplete assessments could affect which participants contribute to the observed percentage and how the analysis treats participants without an assessment. The stated primary population includes randomized participants who received at least 1 dose, but that population definition does not specify what happens when Week 10 data are unavailable. The record does not report imputation, a missing-equals-no-remission rule, a complete-case approach, or sensitivity analyses, so none should be presumed.

The trial status is terminated, but the reason and its consequences for the analysis population are not reported. The registry entries do not establish whether termination resulted in missing observations, altered follow-up, or a change to the analysis plan. These uncertainties matter because the posted percentages are most informative when the analysis population, assessment completion, and missing-data rules are clear.

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: campylobacter infection (16.7%), proctalgia (14.3%).

The serious adverse event counts are reported by treatment group and phase. During blinded treatment, the registry lists 1 participant with a serious adverse event in the tilpisertib 300 mg group, 0 in the tilpisertib 100 mg group, and 1 in the placebo group. The corresponding numbers at risk were 7, 6, and 6. No deaths are listed for these groups.

Open-label treatment safety groups are reported separately. The group transitioning from blinded tilpisertib 300 mg lists 0 participants with serious adverse events among 4 at risk; the group transitioning from blinded tilpisertib 100 mg lists 0 among 3; and the group transitioning from placebo lists 0 among 3. No deaths are listed for these open-label groups. These are phase-specific safety summaries, not independent randomized treatment comparisons.

The registry identifies Campylobacter infection at 16.7% and Proctalgia at 14.3% among the top serious-event terms. Those percentages are reported as event-term summaries; the registry entries do not establish a treatment-group attribution for either term. Serious adverse event counts are distinct from counts of all treatment-emergent adverse events and laboratory abnormalities.

In general, safety counts describe events observed in the recorded groups, not proof that a treatment caused or did not cause an event. Interpretation also depends on exposure duration, event definitions, follow-up, and how repeat events are counted. Those details are not reported in the registry record. The small group sizes and the separate open-label cohorts limit direct comparisons; no causal conclusion should be drawn from these counts alone.

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

The primary results establish that the registry recorded 0.0 as the Week 10 remission percentage for each blinded-treatment arm. This is a clear description of what was posted for this endpoint in the analysis population. It does not establish that tilpisertib and placebo have the same effect, because the registry does not report an estimable comparison or its uncertainty. Nor does it show that every participant had the same disease course: the endpoint records whether a participant met a particular combination of symptom and endoscopic criteria at the assessment.

The results also do not establish a precise population remission rate. General statistical interpretation distinguishes an observed sample percentage from the unknown rate in a broader population. An interval estimate can show how uncertain that estimate is, but no primary-endpoint interval is reported. The small arm sizes and the absence of observed remissions make it especially important not to treat the displayed percentages as a complete account of the range of plausible outcomes.

The terminated status is relevant context, but the registry record does not report why the study was terminated or what consequences that had for data collection and analysis. That status alone does not establish that termination was related to efficacy, safety, or any particular operational issue. The listed secondary outcomes likewise do not establish findings when their results are not reported in the registry record.

The safety figures describe reported serious adverse events and deaths in the stated groups. They do not, by themselves, establish causation, comparative safety, or the absence of other adverse events. The open-label groups reflect later treatment exposure and should not be read as randomized arms. The registry's top serious-event terms are descriptive and do not identify a comparative effect.

Overall, the posted record permits a narrow descriptive conclusion about the recorded primary outcome and safety counts. It does not support a quantified treatment contrast, a claim of equivalence, or a definitive conclusion about efficacy or safety. Those interpretations would require information not reported in the registry record, including comparative estimates, uncertainty intervals, analysis methods, and details of missing data and follow-up.

14. Why This Trial Matters Statistically

This trial illustrates a basic distinction in clinical-trial reporting: an outcome can be clearly defined and summarized while the treatment comparison remains unavailable. The primary endpoint uses an explicit clinical-remission rule based on stool frequency, rectal bleeding, and endoscopic findings. The posted percentages are 0.0 in all three blinded-treatment arms, yet a two-arm comparison is not estimable. A reader therefore has descriptive arm results but no reported estimate of the contrast that the randomized design was meant to inform.

That distinction matters because percentages alone do not communicate precision. In general, an estimate is more useful when accompanied by an uncertainty interval and a clear account of the analysis population and method. Small denominators can leave substantial uncertainty even when the observed percentage appears unambiguous. The registry record does not report a primary comparison, interval, or test, so the apparent similarity of the observed values cannot be translated into evidence that the treatments are equivalent.

The record also highlights why design information and analysis reporting serve different purposes. Randomization and double masking are relevant safeguards, but they do not replace a transparent account of how outcomes were analyzed, how missing measurements were handled, or how multiple endpoints were interpreted. Those statistical details are not reported in the registry record. A terminated status adds context but, without a reported reason or analysis impact, cannot explain the pattern of results.

Finally, the safety summaries demonstrate the importance of separating blinded randomized groups from later open-label exposure groups. Counts from these different phases answer different descriptive questions and cannot be combined as if all participants had remained in comparable randomized conditions. Careful attention to denominators, treatment phase, and outcome definition is essential for a valid reading of both efficacy and safety reporting.

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 available primary outcome consists of three arm-level percentages and their denominators. No comparative estimate, confidence interval, or p-value is reported, and the registry states that a two-arm comparison for this binary endpoint is not estimable. The data therefore do not quantify the comparative effect or its precision.

The primary outcome groups are small: 7 participants in the tilpisertib 300 mg arm, 6 in the tilpisertib 100 mg arm, and 6 in the placebo arm. The recorded percentage is 0.0 in each group. These observed results have limited ability to characterize response frequencies beyond the participants represented in the record. The registry record does not report additional results that would provide an alternative comparative view.

The study is listed as terminated, but the reason for termination and any impact on recruitment, follow-up, or analysis are not reported in the registry record. The record does not report the number of participants with missing Week 10 assessments, the rules for handling missing data, or sensitivity analyses. It also does not provide a statistical analysis plan, details of the randomization process, or methods for addressing multiple outcomes.

The safety summaries cover both blinded and open-label groups. The open-label groups reflect participants' prior response status and treatment history, so they are not direct substitutes for randomized comparisons. Exposure duration and the detailed definitions used in safety summaries are not reported in the registry record. The serious-event term percentages are descriptive and are not accompanied by treatment-specific comparative analyses.

These limitations constrain interpretation to the reported descriptive findings. They do not identify why results or methods are absent, and they do not show whether additional information exists outside the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of Tilpisertib in Adults With Moderately to Severely Active Ulcerative Colitis — NCT04130919.
• Registry record last updated 2022-08-24; status last verified 2022-07.
• Results first posted 2022-08-24.
• 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

NCT04130919 is a terminated Phase 2, randomized, double-blind, parallel-group, placebo-controlled study of tilpisertib in adults with moderately to severely active ulcerative colitis. The registry lists 19 enrolled participants and a primary completion date of 2021-02-25. The reason for termination is not reported in the registry record.

The primary outcome was clinical remission per modified MCS at Week 10, in randomized participants who received at least 1 dose of study drug. Posted percentages were 0.0 for tilpisertib 300 mg, 0.0 for tilpisertib 100 mg, and 0.0 for placebo. No two-arm comparison was estimable. The registry lists six secondary outcomes and reports serious adverse event counts across blinded and open-label treatment groups, with no deaths listed. Comparative efficacy, uncertainty intervals, analysis details, missing-data handling, and the reason for termination are not reported in the registry record.