Study to Evaluate the Clinical Activity and Safety of Oral NX-13 in Moderate to Severe Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Clinical Activity and Safety of Oral NX-13 in Moderate to Severe Ulcerative Colitis (NCT05785715), a randomized phase 2 study. The primary outcome is Change From Baseline in Modified Mayo Score (MMS) at Week 12.

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, placebo-controlled, multiple-dose, multicenter Phase 2 induction study with a long-term extension. The registry record describes NX-13 doses of 250 mg and 750 mg, alongside matching placebo. It lists a parallel-group model and quadruple masking. Participants were instructed to take three tablets per day, with dosing recommended at the same time each day for consistency.

The registry record reports enrollment of 81 participants. For the primary endpoint, the posted induction groups include 33 participants in the NX-13 250 mg group, 33 in the NX-13 750 mg group, and 15 in the placebo group. The primary population is described as randomized participants who received at least 1 dose of study drug. The record lists ulcerative colitis as the condition and describes the study population as having moderate to severe disease.

The study status is terminated. The record lists a start date of 2023-04-24 and a primary completion date of 2025-05-30. These administrative details do not by themselves explain why the study was terminated or establish whether termination affected the results. The reason for termination and its statistical implications are not reported in the registry record. The trial’s original sample-size justification, planned statistical analysis details beyond the posted outcome information, and any interim analyses are not reported in the registry record.

The Week 12 primary outcome is change from baseline in modified Mayo Score. The registry record also lists secondary clinical, endoscopic, histopathology, and safety outcomes. The induction and long-term extension safety groups are reported separately; their participant counts should not be treated as if they represented a single concurrent 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.

Before assignment: A total of 159 participants were screened. A total of 81 participants were randomized and received at least 1 dose of study treatment. After completion of induction period, participants were eligible to enter a long-term extension period (LTE). Participants who received NX-13 250 or 750 mg during the induction period continued to receive the same blinded dose during the LTE. Participants who received placebo during the induction period were randomized to receive blinded NX-13 250 or 750 mg.

Induction Period

Reasons for not completing this period:

Long Term Extension

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ITT population 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: The intent to treat (ITT) population included all randomized participants who received at least 1 dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Modified Mayo Score (MMS) at Week 12, measured over Baseline, Week 12.

The primary endpoint is change from baseline in modified Mayo Score at Week 12. The score combines three subscores: stool frequency, rectal bleeding, and findings on endoscopy. Each subscore ranges from 0, normal, to 3, severe disease; the total ranges from 0, normal or inactive disease, to 9, severe disease. Lower scores indicate better health status, and a negative change indicates improvement.

A change score summarizes how the measured condition differs from the participant’s baseline value at the selected follow-up time. Comparing average changes between randomized groups can help describe how the groups’ measured outcomes differ over the induction period. The registry record reports least-squares mean changes with standard errors for each group and sponsor-reported least-squares mean differences for the treatment-versus-placebo comparisons.

In general, a composite endpoint combines multiple related measurements into a single summary. This can capture several aspects of a condition while producing one primary outcome for comparison. The meaning of a composite depends on its components and scoring rules, so the reported scale direction matters: a lower modified Mayo Score and a more negative change are favorable directions on the score itself. The endpoint does not, by itself, establish the importance of any particular component or describe outcomes beyond the measured score and time point. The detailed protocol rationale for selecting this endpoint is not reported in the registry record.

7. Results Posted in the Registry

• Induction Period: NX-13 250 mg: mean -2.29 versus -2.11 on control; difference -0.18 (95% CI -1.59 to 1.23), standardized effect d = -0.08; z-test p = 0.802.
• Induction Period: NX-13 750 mg: mean -1.98 versus -2.11 on control; difference 0.13 (95% CI -1.27 to 1.53), standardized effect d = 0.06; z-test p = 0.855.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Number of Participants With Clinical Remission Per MMS at Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Induction Period: NX-13 250 mg: 12.1% (4/33) versus 13.3% (2/15) on control; risk difference -1.2 percentage points (95% CI -21.7 to 19.3), risk ratio 0.91 (0.19–4.43); unadjusted two-proportion z-test p = 0.906.
  • Induction Period: NX-13 750 mg: 15.2% (5/33) versus 13.3% (2/15) on control; risk difference 1.8 percentage points (95% CI -19.3 to 22.9), risk ratio 1.14 (0.25–5.21); unadjusted two-proportion z-test p = 0.869.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Induction Period: NX-13 250 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Induction Period: NX-13 750 mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With MMS <=2 at Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Induction Period: NX-13 250 mg: 24.2% (8/33) versus 20.0% (3/15) on control; risk difference 4.2 percentage points (95% CI -20.7 to 29.2), risk ratio 1.21 (0.37–3.94); unadjusted two-proportion z-test p = 0.746.
  • Induction Period: NX-13 750 mg: 21.2% (7/33) versus 20.0% (3/15) on control; risk difference 1.2 percentage points (95% CI -23.4 to 25.8), risk ratio 1.06 (0.32–3.55); unadjusted two-proportion z-test p = 0.924.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Induction Period: NX-13 250 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Induction Period: NX-13 750 mg and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Robarts Histopathology Index (RHI) Score <=3 at Week 12

• Endpoint type: Binary: the number of participants with the event, compared as proportions.
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • Induction Period: NX-13 250 mg: 24.2% (8/33) versus 6.7% (1/15) on control; risk difference 17.6 percentage points (95% CI -1.7 to 36.9), risk ratio 3.64 (0.50–26.53); unadjusted two-proportion z-test p = 0.148.
  • Induction Period: NX-13 750 mg: 33.3% (11/33) versus 6.7% (1/15) on control; risk difference 26.7 percentage points (95% CI 6.2 to 47.1), risk ratio 5.00 (0.71–35.28); unadjusted two-proportion z-test p = 0.048.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between Induction Period: NX-13 250 mg and the control. The interval gives the range of effects that remain compatible with the data.
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for Induction Period: NX-13 750 mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The posted secondary outcomes cover clinical remission, a modified Mayo Score threshold, histopathology, clinical response, and endoscopic response and remission, as well as adverse events. Three Week 12 secondary outcomes have participant counts and recalculated comparisons available in the posted results. Across those outcomes, the observed counts do not form a single consistent pattern: some NX-13 groups have higher counts than placebo on a measure, while other group counts are closer. The recalculated estimates also vary in direction and precision.

These outcomes complement the primary modified Mayo Score change by examining different definitions of clinical status and other aspects of disease assessment. They do not replace the primary endpoint or establish a separate conclusion about the overall treatment comparison. The primary mean-change estimates have confidence intervals that include zero and are broad; the secondary findings should be interpreted alongside that uncertainty rather than used to turn an uncertain primary result into a definitive claim.

In general, examining many outcomes increases the chance that some results will appear notable by chance, even when there is no corresponding underlying effect. This is why multiplicity procedures and a clear distinction between prespecified and exploratory outcomes matter. The registry record lists secondary outcomes, but the multiplicity strategy and the prespecified inferential hierarchy are not reported in the registry record. The recalculated secondary comparisons are unadjusted. They therefore carry less inferential weight than a result interpreted within a fully reported, prespecified analysis plan.

Counts are also particularly sensitive to the small group sizes and to how each outcome is defined and measured. In general, a small change in the number of participants meeting a binary definition can materially change a proportion or its uncertainty when denominators are limited. The wide intervals in some recalculated comparisons reflect that limited precision. The overall secondary pattern is descriptive and does not resolve the uncertainty in the primary comparison.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Number of Participants With Treatment-emergent Adverse Events (TEAEs) During the Induction Period
• Number of Participants With Treatment-emergent Serious Adverse Events (TESAEs) During the Induction Period
• Number of Participants With Clinical Remission Per MMS at Week 12
• Number of Participants With MMS <=2 at Week 12
• Number of Participants With Robarts Histopathology Index (RHI) Score <=3 at Week 12
• Number of Participants With Clinical Response Per MMS at Week 12
• Number of Participants With Endoscopic Response at Week 12
• Number of Participants With Endoscopic Remission at Week 12

9. Statistical Interpretation

10. Statistical Methods Explained

What does a mean change describe?

The primary endpoint is continuous: it is a score measured on a numerical scale, and the reported summary is a least-squares mean. The arm-level values are -2.29 for NX-13 250 mg, -1.98 for NX-13 750 mg, and -2.11 for placebo. A group mean describes the center of the observed measurements as summarized by the reported analysis; it does not describe every participant’s result. The standard errors are 0.41, 0.4, and 0.59, respectively. In general, a standard error describes the statistical uncertainty around an estimated mean, rather than the spread of individual participant scores.

What does a between-group estimate mean?

A mean difference compares the reported change in one group with the change in the comparator group. The posted sponsor estimates are least-squares mean differences: -0.18 for NX-13 250 mg versus placebo, and 0.12 for NX-13 750 mg versus placebo. Given the scale direction, a negative contrast numerically favors the NX-13 group on this score, while a positive contrast numerically favors placebo. These are estimates, not definitive statements about the underlying group difference. The sponsor analysis method is not reported in the registry record.

The recalculations are simple, unadjusted comparisons based on posted summary statistics. They yield mean differences of -0.18 and 0.13, respectively. The recalculation uses an approximate pooled standard deviation derived from group standard errors and sample sizes, as indicated in the calculation details. In general, a pooled standard deviation is a measure of outcome variability used to express a difference relative to the scale’s variability. An approximation based on summaries may not reproduce an analysis that uses participant-level observations, covariate adjustment, or another model. The sponsor’s reported analysis and the unadjusted recalculation therefore answer related but not identical statistical questions.

How should a confidence interval be read?

A confidence interval gives a range of values compatible with the estimate under the statistical method and its assumptions. It conveys precision as well as direction: a narrower interval leaves a smaller range of plausible values, while a wider interval leaves more uncertainty. The sponsor reports 90% confidence intervals; the simple recalculations report 95% confidence intervals. Since the confidence levels differ, those intervals should not be compared as though they were generated on the same basis. In general, a confidence interval that includes zero for a difference does not rule out either direction of difference at that interval’s confidence level.

The sponsor’s 90% interval is -1.33 to 0.97 for the 250 mg comparison and -1.03 to 1.28 for the 750 mg comparison. The recalculated 95% intervals are -1.588 to 1.228 and -1.267 to 1.527. Each includes zero, and each covers both negative and positive contrasts. The interval widths indicate that the posted comparisons do not precisely distinguish a small effect from a range of larger differences in either direction.

What does an unadjusted p-value say?

The recalculated unadjusted p-values are 0.802 for 250 mg and 0.855 for 750 mg. In general, a p-value describes how compatible the observed data are with a specified null hypothesis under the chosen statistical model; it is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. These recalculated values are not reported sponsor p-values. The registry record does not report p-values for its sponsor comparisons.

The recalculated p-values are unadjusted, meaning no correction for the number of comparisons is applied in those calculations. The registry record does not report the overall multiplicity strategy. Without that information, the recalculated p-values should be treated as descriptive statistical summaries rather than as a complete account of the trial’s prespecified inferential procedure.

Why do assumptions matter?

Statistical estimates depend on the analysis population, outcome distribution, model, and handling of missing measurements. In general, model-based least-squares means can account for features of the analysis specified in the model, whereas simple calculations from group summaries may not. The record identifies an ITT population as randomized participants who received at least 1 dose of study drug, but it does not report all details needed to reconstruct the sponsor’s model or its handling of missing primary endpoint data. The posted values should therefore be read with the method distinction in mind.

The registry record reports that the primary outcome is continuous and that the group summaries are least-squares means with standard errors. It does not report the sponsor’s analysis method, adjustment variables, missing-data method, or whether any sensitivity analyses were performed. Those omissions limit the ability to assess how the sponsor’s model choices affect the reported contrasts. The unadjusted recalculations are useful as a transparent comparison based on posted summaries, but they cannot fill in unreported analysis details.

In general, a statistical result is most interpretable when the endpoint, population, time point, contrast, and analysis method are considered together. For this study, the endpoint and Week 12 time point are specified, and the primary population is described. Important aspects of the sponsor’s statistical plan are not reported in the registry record. That uncertainty is separate from the numerical uncertainty represented by the confidence intervals.

11. Confidence Intervals and Precision

The primary comparisons are estimated with substantial uncertainty. For NX-13 250 mg versus placebo, the sponsor-reported difference is -0.18 and its 90% confidence interval extends from -1.33 to 0.97. For NX-13 750 mg versus placebo, the reported difference is 0.12, with a 90% interval from -1.03 to 1.28. Each interval spans zero and includes contrasts in both directions. The point estimates alone therefore provide an incomplete account of what the data allow.

The unadjusted recalculations give 95% confidence intervals from -1.588 to 1.228 for 250 mg and from -1.267 to 1.527 for 750 mg. These intervals also include zero and allow a broad range of possible differences. They are not directly interchangeable with the sponsor’s 90% intervals because the confidence levels and calculation methods differ. The registry record does not report the sponsor analysis method, so the intervals should be understood in their respective contexts rather than treated as matching versions of the same calculation.

In general, a confidence interval’s width reflects statistical precision: greater width means greater uncertainty about the size and direction of the underlying contrast. These intervals do not isolate a narrow range around the point estimates. The group sizes were 33 participants in each NX-13 induction group and 15 in placebo, and the reported standard errors were 0.41, 0.4, and 0.59 for the 250 mg, 750 mg, and placebo groups, respectively. The trial’s original sample-size justification is not reported in the registry record.

Interval precision is not the same as clinical importance. The registry record does not provide a threshold for a clinically meaningful modified Mayo Score difference, so the intervals cannot be classified against such a threshold using the posted information. They describe statistical uncertainty in the contrasts, not the probability that any particular effect is true.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The planning figures are illustrations based on observed effects, not the trial’s original design calculations. For the continuous primary endpoint, the figures are participants per arm. The assumptions listed for these calculations are a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect to detect set to the stated fraction of the observed effect. The trial’s own original design assumptions are not reported in the registry record.

The 80% power column gives the illustrative number of participants per arm for a design with an 80% chance of detecting the selected effect under the listed assumptions, if that effect and those assumptions applied. The 90% power column gives the corresponding per-arm planning number for a 90% chance under those same assumptions. In general, higher target power requires more participants when other assumptions are held fixed. Smaller effects need more participants to distinguish them from random variation, which is why the illustrations increase when planning for 75% or 50% of the observed effect rather than 100%.

For the primary comparison with NX-13 250 mg, the illustration for 100% of the observed effect is 2,640 participants per arm for 80% power and 3,534 for 90% power. For NX-13 750 mg, the corresponding figures are 4,888 and 6,544 participants per arm. The corresponding planning entries for smaller fractions of the observed effects are also displayed with the calculation results. These figures are very sensitive to the observed effect estimate, especially when that estimate is small, so they are not forecasts of what a future study will require.

These are planning illustrations, not observed power. They do not describe the chance that the completed study would detect an effect based on its results, and they do not explain why the original trial enrolled its participants. The study’s reported primary outcome groups contain 33 participants in each NX-13 arm and 15 in placebo; those observed group sizes are distinct from the illustrative planning figures.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, Δ is the difference in means to detect and σ is the common standard deviation.

Worked calculation for this trial

1. Observed difference Δ = -0.180; pooled standard deviation σ = 2.334.
2. n = 2 × (1.96 + 0.842)² × 2.334² / -0.180² = 2,639.6, rounded up to 2,640 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
delta <- -0.18                      # observed difference in means
sigma <- 2.3341258488481                     # pooled standard deviation
n_per_arm <- function(power, frac = 1) {
  ceiling(round(2 * (z_a + qnorm(power))^2 * sigma^2 / (delta * frac)^2, 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Check against R's built-in function (t-based, so very slightly larger)
cat("power.t.test:", round(power.t.test(delta = delta, sd = sigma, power = 0.80)$n, 1), "\n")

# Simulation: exact two-sample t-test using simulated means and variances
set.seed(5785715)
n    <- n_per_arm(0.80)
reps <- 20000
m_diff <- rnorm(reps, delta, sigma * sqrt(2 / n))             # difference in sample means
s2     <- sigma^2 * rchisq(reps, 2 * (n - 1)) / (2 * (n - 1))   # pooled sample variance
tstat  <- m_diff / sqrt(s2 * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(tstat) > qt(0.975, 2 * (n - 1))), reps))

Output from running the code

100% of observed effect: n per arm = 2,640 (80% power), 3,534 (90% power)
 75% of observed effect: n per arm = 4,693 (80% power), 6,283 (90% power)
 50% of observed effect: n per arm = 10,559 (80% power), 14,135 (90% power)
power.t.test: 2640.6 
Simulated power at n = 2,640 per arm: 0.799 (20000 replicates)

The simulation draws many sets of group means and variances at the planned sample size and counts how often the two-sample t-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The sponsor-reported primary comparisons are least-squares mean differences with 90% confidence intervals. For NX-13 250 mg versus placebo, the reported difference is -0.18 with an interval from -1.33 to 0.97. For NX-13 750 mg versus placebo, it is 0.12 with an interval from -1.03 to 1.28. The registry record does not report p-values or the method used for these sponsor analyses.

The simple unadjusted recalculations use the posted group summaries and yield differences of -0.18 for 250 mg and 0.13 for 750 mg. Their 95% confidence intervals are -1.588 to 1.228 and -1.267 to 1.527, with unadjusted p-values of 0.802 and 0.855. The differences between these recalculated values and sponsor-reported values are small in the displayed estimates, but their intervals are not directly comparable: the sponsor intervals are 90%, and the recalculated intervals are 95%. The recalculation also uses a different, unadjusted approach.

The posted information does not flag a discrepancy between the sponsor’s analysis and the recalculation. Still, the recalculation cannot reproduce an analysis whose method is not described in the registry record. It is best read as a check based on summary statistics, while the sponsor’s reported least-squares comparisons remain the registry’s own analysis results.

15. Multiplicity, Missing Data and Analysis Populations

The study reports a primary endpoint and multiple secondary outcomes. When several outcomes or treatment comparisons are tested, the chance of at least one apparently unusual result can increase. In general, multiplicity methods control or describe this issue through choices such as a testing hierarchy, adjusted significance thresholds, or a clear designation of analyses as exploratory. The multiplicity approach for this study is not reported in the registry record.

The registry record does not report whether the sponsor used a prespecified hierarchy across the primary and secondary outcomes, adjusted for the two dose comparisons, or applied any other multiplicity procedure. It also does not report interim analyses or stopping rules. Therefore, the recalculated p-values should be regarded as unadjusted summaries, not as evidence that accounts for all outcomes and comparisons in the study.

The primary population is described as the ITT population, including all randomized participants who received at least 1 dose of study drug. The primary arm-level analysis counts are 33, 33, and 15. The precise relationship between that population definition and the data available for every Week 12 measurement is not further described. The method used to handle missing primary outcome measurements, protocol deviations, or other incomplete data is not reported in the registry record.

Missing-data methods can affect estimates when outcome values are unavailable, and their appropriateness depends on why values are missing and on the analysis assumptions. In general, sensitivity analyses can help assess whether conclusions change under alternative assumptions about missing outcomes. Such methods and sensitivity analyses are not reported in the registry record.

The reported primary analyses are least-squares mean comparisons, but their model specification is not reported. The adjustment variables, variance estimation details, and other model assumptions are therefore not available for assessment. These are limits on evaluating the statistical plan; they are not evidence that any particular analysis choice was made.

16. 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: colitis ulcerative (6.1%), altered state of consciousness (3.0%), abdominal pain (2.8%), gastrointestinal tract adenoma (2.8%).

The induction safety summaries report 2 participants with treatment-emergent serious adverse events among 33 at risk in the NX-13 250 mg group, 2 among 33 in the NX-13 750 mg group, and 0 among 15 in the placebo group. These are participant counts, not counts of all serious-event episodes. The registry record also lists 12 participants with other treatment-emergent adverse events among 33 in the 250 mg group, 8 among 33 in the 750 mg group, and 4 among 15 in placebo. No deaths are reported in these induction groups.

The long-term extension summaries are separate: 2 participants with serious adverse events among 36 at risk in the NX-13 250 mg group, and 0 among 32 in the NX-13 750 mg group. Other adverse events are reported for 10 among 36 and 5 among 32, respectively. No deaths are reported in these extension groups. These groups and periods should be read separately from the randomized induction comparison.

The registry lists serious adverse-event terms including ulcerative colitis, altered state of consciousness, abdominal pain, and gastrointestinal tract adenoma, with percentages of 6.1%, 3.0%, 2.8%, and 2.8%, respectively. The record does not provide enough detail in these summaries to establish causation or compare event rates with adjustment for exposure time. Safety counts describe what was reported; they do not by themselves establish a treatment-related risk or absence of risk.

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

The results describe Week 12 modified Mayo Score changes and selected secondary and safety outcomes among participants in this Phase 2 study. The primary group means were negative in all three induction groups, and the between-group estimates were close to zero in the reported sponsor analysis. Both sponsor-reported confidence intervals include zero, and the simple recalculated intervals also include zero. The posted estimates therefore do not establish a clear difference between either NX-13 dose and placebo on the primary endpoint.

That interpretation is not the same as concluding that the groups are identical. The intervals allow a range of possible contrasts in both directions, and they are not narrow enough to exclude all potentially important differences. The registry record does not report a threshold for a clinically meaningful difference on this endpoint, so statistical uncertainty cannot be translated into a judgment about clinical importance using these results alone.

Nor do the results establish that NX-13 works or does not work. A trial estimate is an uncertain summary of outcomes in a particular study population, at a particular time point, under a particular analysis. Here, the study is listed as terminated, and the reason for termination is not reported in the registry record. The available results cannot explain the termination or show whether it affected the analysis.

Secondary counts and safety summaries provide additional descriptive information, but multiple secondary comparisons and limited group sizes make those results uncertain. The multiplicity approach, detailed missing-data handling, and sponsor analysis method are not reported in the registry record. Such information would be relevant to a fuller assessment of the strength and robustness of the statistical evidence.

In general, statistical evidence should be interpreted with attention to both effect estimates and their precision, rather than by relying only on whether a result crosses a threshold. The posted results support a description of the observed outcomes and uncertainty. They do not support a definitive conclusion about the effect of NX-13 beyond the comparisons and measures reported for this study.

18. Why This Trial Matters Statistically

This trial illustrates why the treatment contrast matters more than reading arm-level change scores in isolation. All three primary groups had negative average changes, but the comparisons ask whether those changes differed between each NX-13 dose and placebo. The sponsor-reported estimates are near zero and their 90% confidence intervals include differences in both directions. That distinction prevents within-group change from being mistaken for evidence of a between-group effect.

It also shows the importance of reading estimates together with precision. The posted treatment contrasts are not precise enough to tightly constrain the range of compatible differences. A point estimate is one summary of the data, but its interval shows how much uncertainty remains. The registry record lists 33 participants in each NX-13 induction group and 15 in placebo, and the resulting summaries should be considered in that context.

The secondary outcomes make another statistical issue visible: multiple measures can yield a varied pattern of counts and estimates. Without a reported multiplicity plan, it is difficult to know how those results fit into the study’s intended confirmatory testing strategy. This matters especially when some secondary comparisons look more pronounced than the primary result; isolated findings should not be given the same weight as a prespecified, appropriately interpreted primary analysis.

Finally, the comparison between sponsor-reported estimates and simple unadjusted recalculations demonstrates why method and confidence level matter. Similar point estimates do not mean the analyses are identical. The sponsor reports 90% intervals and least-squares mean differences, while the recalculations use posted summaries and 95% intervals. Understanding those distinctions is essential to a careful statistical reading of registry results.

19. 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 primary outcome summaries are available, but the registry record does not report the sponsor analysis method, model specification, covariate adjustments, or detailed variance assumptions. This limits independent assessment of how the reported least-squares mean differences were obtained. The recalculations are unadjusted and based on group summary statistics, so they cannot reproduce a participant-level model or address unreported adjustments.

The trial’s original sample-size justification is not reported in the registry record. The separate planning illustrations are based on observed effects and specified assumptions; they should not be mistaken for the design rationale. The record also does not report the reason the study was terminated, whether termination affected planned follow-up, or whether any interim analyses occurred.

Missing-data procedures for the primary and secondary outcomes are not reported in the registry record. The record describes the ITT population as randomized participants who received at least 1 dose, but further details about availability of outcome measurements and the analysis population for each endpoint are not reported. This limits assessment of how incomplete Week 12 data may have influenced the summaries.

The primary sponsor intervals are 90%, while the simple recalculations use 95% intervals, so they are not directly interchangeable. The secondary comparisons are unadjusted, and the multiplicity strategy is not reported. Several secondary measures are represented by participant counts in relatively limited groups, making estimates sensitive to the observed counts and potentially imprecise.

Finally, safety summaries report participant counts across induction and extension periods, but these are separate groups and periods. The posted summaries do not establish causation or provide all information needed to compare exposure-adjusted risks. These limitations constrain interpretation of the registry record; they do not establish that a particular unreported method or outcome occurred.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Study to Evaluate the Clinical Activity and Safety of Oral NX-13 in Moderate to Severe Ulcerative Colitis — NCT05785715.
• Registry record last updated 2026-06-15; status last verified 2026-05.
• Results first posted 2026-06-15.
• 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.

23. Record Summary

NCT05785715 is a randomized, quadruple-masked, parallel-group Phase 2 study of oral NX-13 in participants with moderate to severe ulcerative colitis. It compared NX-13 250 mg and 750 mg with matching placebo in an induction period and included a long-term extension. The registry record reports enrollment of 81 and lists the study status as terminated.

The primary outcome was change from baseline in modified Mayo Score at Week 12. Sponsor-reported least-squares mean differences versus placebo were -0.18 for NX-13 250 mg and 0.12 for NX-13 750 mg; both reported 90% confidence intervals include zero. Simple unadjusted recalculations also have confidence intervals that include zero. The results are uncertain and do not establish a definitive between-group difference.

Secondary outcomes and safety counts provide additional descriptive information. The multiplicity strategy, missing-data methods, sponsor analysis method, original sample-size justification, and reason for termination are not reported in the registry record.