Study of Efficacy, Safety, and Tolerability of LYS006, in Patients With Mild to Moderate Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy, Safety, and Tolerability of LYS006, in Patients With Mild to Moderate Ulcerative Colitis (NCT04074590), a randomized phase 2 study. The primary outcome is Clinical Remission Rate at the End of the Study Treatment.

2. Clinical Question

The study asked whether LYS006 was associated with a different clinical remission rate from placebo at the end of study treatment. Participants were adults with mild to moderate ulcerative colitis. The primary endpoint was assessed at Week 8 and defined remission using the full Mayo score and its component subscores.

This is a question about an observed endpoint and its uncertainty, not a direct measure of every aspect of ulcerative colitis or of longer-term outcomes. The registry record describes the study as intended to assess preliminary efficacy, safety, and tolerability and to inform whether LYS006 had an adequate clinical profile for further development. The record lists one secondary outcome concerning treatment-emergent adverse events and serious adverse events.

3. Trial Design

NCT04074590 is a Phase 2, randomized, double-blind, parallel-group study comparing LYS006 with placebo in patients with mild to moderate ulcerative colitis. The official title describes it as a multi-center study in which subjects and investigators were blinded. The two arms were LYS006 20mg and placebo. The sponsor was Novartis Pharmaceuticals.

The registry lists enrollment of 23 participants. The study began on 2020-02-03, and the primary completion date was 2022-11-07. Its status is TERMINATED. The reason for termination is not reported in the registry record, so the status alone does not establish why the study ended or whether the planned objectives were completed.

The primary outcome was clinical remission rate at the end of study treatment, with a Week 8 timeframe. The arm entries report 14 participants for LYS006 20mg and 7 for placebo for this outcome. The primary analysis population is defined as participants who received any study drug and had no protocol deviations with relevant impact on pharmacodynamic data. Safety counts use a different set of at-risk group sizes: 16 for LYS006 20 mg and 7 for placebo. The registry record does not explain the difference between the endpoint arm counts and the safety at-risk counts.

Randomization and blinding are design features intended to support a fair comparison and reduce the influence of expectations on study conduct or assessment. The registry record does not report the randomization procedure, how blinding was maintained, or whether the study had additional design features beyond those stated in its title and listed fields. It also does not report a reason for termination or details of the study's planned sample-size justification.

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: After signing informed consent, screening evaluations took place from Day -28 to Day -1. During that period all safety and other assessments were performed to evaluate eligibility. Eligible patients returned for the Baseline visit on Day 1. Eligibility was confirmed prior to randomization and required baseline assessments were completed prior to dosing on Day 1.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The PD analysis set included all participants who received any study drug and had no protocol deviations with relevant impact on PD data.

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.

6. Primary Endpoint

The registry lists the primary outcome as Clinical Remission Rate at the End of the Study Treatment, measured over Week 8.

The primary endpoint is the clinical remission rate at Week 8, expressed as the percentage of participants meeting a specified Mayo score definition. The Mayo score measures ulcerative colitis activity through stool frequency, rectal bleeding, endoscopic findings, and the Physician's Global Assessment. Each subscore ranges from 0 to 3, with higher scores indicating more severe disease; the full Mayo score is the sum of the four subscores and ranges from 0 to 12.

For this study, remission required a full Mayo score of 2 points or lower, with no individual subscore exceeding one point. The endpoint is binary at the participant level: each participant either met the remission definition or did not. A remission rate summarizes the share of participants in an arm who met that definition. It is clinically interpretable as a threshold-based outcome, while retaining less detail than the component scores or the full score itself.

The endpoint was analyzed using a binomial model and a Bayesian approach, with baseline total Mayo score and treatment group as explanatory variables. Adjusting for baseline total Mayo score can account for differences in initial disease activity in the model. The registry record does not report additional detail about how the individual components were measured, the handling of assessments that were unavailable, or any other endpoint definitions beyond the remission criteria stated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The endpoint is binary because each participant is classified as either meeting the remission definition or not meeting it. A binomial model is a natural statistical framework for this type of outcome: it represents the number of participants meeting the endpoint in relation to the number assessed. The reported arm-level percentages describe the estimated remission rates. The model comparison then estimates a treatment difference between LYS006 and placebo.

What does the Bayesian analysis represent?

In general, Bayesian analysis combines information from a statistical model with a prior distribution to obtain a posterior distribution for quantities of interest. A posterior estimate summarizes that distribution, while an interval can express the range of values supported by the analysis under its assumptions. The registry labels the reported interval a 90% confidence interval, even though it describes the analysis as Bayesian. The record does not report the prior, computational approach, or further details that would clarify the interval's construction or its interpretation.

The analysis description says baseline total Mayo score and treatment group were explanatory variables. Including baseline score in the model allows the estimated treatment comparison to account for that measured starting characteristic according to the model. The record does not report the precise model specification, any additional covariates, or the form of the treatment contrast beyond calling it a posterior estimate of the treatment difference.

How should the confidence intervals be read?

In general, an interval communicates uncertainty around an estimate rather than guaranteeing that the true value lies within its endpoints. For the LYS006 arm, the reported 90% interval is 0.87 to 23.31; for placebo, it is 5.67 to 24.12. The interval for the estimated treatment difference runs from -18.02 to 13.23. Because the latter includes zero and values in both directions, the posted estimate does not tightly distinguish between a negative and positive treatment difference. The confidence intervals are not the same as a range of individual participants' outcomes.

The record reports two versions of the analysis with identical treatment-difference estimates and interval limits, but different p-values, 0.314 and 0.037. A p-value is a measure defined by a statistical procedure and its assumptions; it is not the probability that a treatment works, nor does it express the size or clinical importance of an effect. Since the record does not explain the discrepancy or define these values further, neither should be used to resolve the uncertainty on its own.

Why does the analysis population matter?

The stated pharmacodynamic analysis set includes participants who received any study drug and had no protocol deviations with relevant impact on pharmacodynamic data. The registry's primary outcome arm entries list 14 participants for LYS006 and 7 for placebo, whereas safety entries list 16 and 7 at risk. An analysis population determines which participants contribute to an endpoint estimate; it is therefore important to distinguish these counts rather than assume they describe an identical set. The reasons for the different LYS006 counts are not reported in the registry record.

General statistical practice also distinguishes the analysis population from the randomized population and the population used for safety summaries. The record does not state whether the primary efficacy analysis followed an intention-to-treat approach, how participants with missing Week 8 assessments were handled, or whether values were imputed. Those details cannot be inferred from the arm counts or from the stated model alone.

What can the planning calculations tell readers?

In general, sample-size calculations are planning exercises that depend on assumptions about the effect to detect, the significance level, allocation, and statistical approximation. The stated planning assumptions use a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the target effect defined as a specified portion of the observed effect. Such calculations are illustrations, not observed power and not evidence that the trial had a particular probability of detecting an effect. The registry record does not report the study's own sample-size justification, so planning illustrations should not be mistaken for the rationale used to set enrollment.

Overall, the model description establishes that the endpoint was treated as binary and that baseline total Mayo score and treatment group were included. Important analytic details—including prior choices, missing-data handling, model diagnostics, interim analyses, and the explanation for the duplicate p-values—are not reported in the registry record.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("LYS006 20mg", "Placebo")
n      <- c(14, 7)
events <- c(1, 1)
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  LYS006 20mg  14  1  7.1  0.2  33.9  1.3  31.5  1.7  31.9
ARM  Placebo  7  1  14.3  0.4  57.9  2.6  51.3  3.2  52.7

11. Analyses Reported by the Sponsor

The posted analysis is described as Bayesian and reports a posterior estimate of the treatment difference of -3.29, with a 90% confidence interval from -18.02 to 13.23. The registry lists this same estimate and interval twice, but the corresponding p-values differ: one is 0.314 and the other is 0.037. No explanation for the two p-values is reported in the registry record, so they cannot be reconciled from the posted information.

The registry record does not provide an estimable recalculated two-arm comparison for this binary percentage endpoint. Consequently, there is no independent recalculated treatment-difference estimate to compare numerically with the posted Bayesian estimate. The two arm-specific percentages remain descriptive summaries, while the posted model-based estimate is the registry's reported comparison.

The record does not identify a discrepancy that would require a recalculated analysis to take precedence. The appropriate reading is therefore to report the posted Bayesian estimate as recorded, while noting its interval and the unexplained difference between the p-values. That qualification is important: neither p-value should be chosen as the definitive one without an explanation of how the entries arose.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists one secondary outcome: the number of participants with treatment-emergent adverse events and serious adverse events. The primary outcome is the Week 8 clinical remission rate. The posted information does not describe a multiplicity-control procedure, a hierarchy of hypotheses, or which outcome was intended to carry confirmatory emphasis. Any adjustment for testing multiple outcomes or analyses is not reported in the registry record.

Missing-data handling is also not described. The record defines the pharmacodynamic analysis set and gives arm counts for the remission endpoint, but it does not say how participants without a Week 8 assessment were treated, whether any data were imputed, or whether sensitivity analyses were performed. A model specification alone does not answer those questions. The effect of missing endpoint data on the estimates therefore cannot be assessed from the registry information.

The record does not describe interim analyses, stopping boundaries, or whether decisions about termination were connected to efficacy or safety findings. These details are not reported in the registry record and should not be inferred from the TERMINATED status. The reason for termination is likewise not reported.

There are two reported entries for the same Bayesian treatment-difference estimate and interval, with p-values of 0.314 and 0.037. The registry does not explain whether these represent different tests, a correction, or a data-entry issue. No particular explanation can be selected on the posted evidence. This ambiguity is distinct from multiplicity adjustment: without further detail, it is not possible to tell whether the values reflect different analyses or some other reporting issue.

Sample-size planning assumptions are described as an illustration based on the observed effect, a two-sided significance level of 0.05, equal allocation, and a normal approximation. The study's own sample-size justification is not reported in the registry record. Such planning calculations are not observed power, and they do not resolve the uncertainties about the analysis population, missing data, or multiplicity.

13. 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

For serious adverse events, the registry lists 0 affected participants among 16 at risk in the LYS006 20 mg group and 0 among 7 at risk in the placebo group. The total entry lists 0 serious adverse events among 23 participants at risk. Deaths are listed as 0 in each arm and in total. No serious-event terms are listed.

These entries mean that the registry reports no serious adverse events or deaths in the stated safety groups during the reporting period. A zero count is not proof that the risk is absent, and these small groups cannot characterize uncommon events precisely. The at-risk counts are not the same as the LYS006 endpoint count, and the record does not explain that difference.

The safety summary also lists other treatment-emergent adverse events in 7 participants at risk in the LYS006 group and 5 in the placebo group. These counts are distinct from serious adverse events. The registry does not provide further detail about event types or severity in the registry record recorded for this analysis. Safety counts should be read as descriptive observations from this study, not as a complete characterization of safety.

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

The results establish what the registry reports for the specified Week 8 remission endpoint: arm-specific percentages, a model-based treatment-difference estimate, and an interval expressing uncertainty. The estimate is -3.29, and its 90% confidence interval extends from -18.02 to 13.23. Because the interval includes values on both sides of zero, it does not identify a clear direction for the treatment difference. The interval also indicates that the point estimate should not be read as a precise effect size.

The results do not establish why the study was terminated, whether missing outcomes changed the findings, or whether the analysis was adjusted for multiple outcomes. Those aspects are not reported in the registry record. The record also has two different p-values attached to otherwise repeated analysis results, and does not explain the difference. That makes a simple significance-based conclusion particularly difficult.

The study was described as an assessment of preliminary efficacy, safety, and tolerability. Its endpoint counts and safety counts involve limited groups, and the LYS006 counts differ between those summaries. The posted estimates should therefore be interpreted in the context of the populations and analysis details actually described, rather than treated as a complete account of all participants or all possible outcomes.

These findings are not a recommendation about treatment. They do not establish a clinical benefit or lack of benefit, and they do not determine the balance of effects for an individual. They are registry results from one terminated Phase 2 study, with uncertainty and reporting limitations that should remain visible in any statistical interpretation.

15. Why This Trial Matters Statistically

This study illustrates why an estimate, its uncertainty, and its reporting context need to be read together. The arm-specific remission percentages are not enough to establish a between-arm difference; the posted Bayesian comparison is more directly relevant to that question. Its interval includes both negative and positive values, so the point estimate cannot stand alone as a precise conclusion.

The duplicate analysis entries also show why internal consistency matters. The treatment-difference estimate and interval are repeated, but the p-values are not. Without an explanation, the reader cannot determine whether the values correspond to distinct tests or reflect another issue. A reported p-value should not override the uncertainty conveyed by the interval, particularly when its relation to the other entry is unclear.

Analysis populations matter as well. The remission arm counts and safety at-risk counts differ for LYS006, while the registry does not explain why. Careful interpretation requires distinguishing the population used for each summary instead of assuming that each number refers to the same set of participants.

Finally, a terminated study with preliminary objectives may still contribute useful statistical information about endpoint definition, model reporting, and uncertainty. At the same time, the termination reason, missing-data approach, multiplicity plan, and study-specific sample-size rationale are not reported in the registry record. Recognizing what is reported—and what remains unknown—helps keep conclusions proportional to the evidence.

16. 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.

Several limitations specific to this trial constrain interpretation. The registry lists enrollment of 23 and endpoint counts of 14 for LYS006 20mg and 7 for placebo. Safety at-risk counts are 16 and 7, respectively. The record does not explain why the LYS006 count differs across these summaries, or how participants not represented in the endpoint counts were handled.

The study status is TERMINATED, but the reason is not reported in the registry record. The record also does not establish whether termination affected planned assessments or analysis. Missing Week 8 outcome handling, imputation, and sensitivity analyses are not described, so the potential influence of incomplete outcome data cannot be assessed.

The primary analysis is described as Bayesian, but prior choices and further model details are not reported. The treatment-difference estimate and interval are repeated in two analysis entries, while the p-values differ. The record offers no explanation for this inconsistency. In addition, no multiplicity procedure or study-specific sample-size justification is reported.

The results concern one binary remission definition at Week 8. They do not by themselves describe changes in each Mayo score component, outcomes beyond that time point, or longer-term safety. The record lists a secondary adverse-event outcome, but further event detail is limited in the information available for this analysis. These limitations call for a cautious reading of the posted estimates rather than an extrapolation beyond the endpoint and study population described.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Study of Efficacy, Safety, and Tolerability of LYS006, in Patients With Mild to Moderate Ulcerative Colitis — NCT04074590.
• Registry record last updated 2024-06-20; status last verified 2024-06.
• Results first posted 2023-11-09.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

20. Record Summary

NCT04074590 is a randomized, double-blind, parallel-group Phase 2 study of LYS006 20mg versus placebo in adults with mild to moderate ulcerative colitis. The registry lists 23 participants and a TERMINATED status. The primary outcome was clinical remission at Week 8, defined using the full Mayo score and its subscores.

Reported remission percentages were 8.95 for LYS006 and 12.24 for placebo. The Bayesian treatment-difference estimate was -3.29, with a 90% confidence interval from -18.02 to 13.23. Two analysis entries give different p-values, 0.314 and 0.037, without an explanation. The registry reports no serious adverse events or deaths in either safety group. The reason for termination, missing-data handling, and several other analysis details are not reported in the registry record.