A Study With GB004 in Adult Subjects With Active Ulcerative Colitis (UC): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study With GB004 in Adult Subjects With Active Ulcerative Colitis (UC) (NCT04556383), a randomized phase 2 study. The primary outcome is Percentage of Participants With Clinical Remission at PCP Week 12.

2. Clinical Question

The registry lists the study as a Phase 2 randomized, double-blind, placebo-controlled, multicenter trial with parallel groups. Its primary endpoint was clinical remission at PCP Week 12. The posted percentages were 17.9% for placebo, 15.4% for GB004 480 mg once daily, and 22.5% for GB004 480 mg twice daily. These are observed proportions, not estimates that establish a treatment effect on their own. The comparisons need to be read alongside their confidence intervals and the registry's reported analyses.

The question is specific to the endpoint definition, population, and assessment time. It is not a general test of every possible benefit or risk of GB004, nor does the primary result summarize the open-label extension. The record does not report why the study was terminated.

3. Trial Design

This was a Phase 2 randomized, double-blind, placebo-controlled, multicenter study with a parallel-group model. The registry reports enrollment of 236 and lists the study status as terminated. The study had a 36-week placebo-controlled period (PCP), followed by a 24-week open-label extension (OLE). The stated purpose was to assess the efficacy and safety of two GB004 dose regimens when added to background UC therapy of 5-aminosalicylate, with or without systemic steroids.

In the PCP, the listed groups were placebo, GB004 480 mg once daily, and GB004 480 mg twice daily. The primary endpoint was assessed at PCP Week 12, although the placebo-controlled period continued for 36 weeks. The open-label extension used GB004 480 mg twice daily for 24 weeks. Because this extension was open label, it is distinct from the blinded randomized placebo comparison and should not be read as another randomized comparison against placebo.

The primary endpoint population is described as the PCP Intent to Treat population, consisting of randomized participants who received at least one dose of PCP study treatment. Endpoint-specific denominators can differ, as in the histologic remission analysis. The registry record does not report the reason for termination, the original sample-size justification, the protocol's statistical analysis plan, or whether interim analyses were planned or conducted. Those details cannot be inferred from the posted endpoint results.

Randomization and masking are features intended to support a fair comparison by limiting systematic differences and knowledge-related influences. They do not eliminate uncertainty, and the posted results still require interpretation in light of the outcome definitions, analysis population, confidence intervals, and missing-data information. The registry lists 11 outcome measures and 20 analyses overall.

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.

PCP

Reasons for not completing this period:

OLE

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: PCP Intent to Treat (ITT) Population: all participants who were randomized and received at least 1 dose of PCP study treatment

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 Percentage of Participants With Clinical Remission at PCP Week 12, measured over At PCP Week 12.

The primary endpoint was the percentage of participants with clinical remission at PCP Week 12. The registry defines remission as a Modified Mayo score of at most 2, with a rectal bleeding subscore of 0, a stool frequency subscore of 0 or 1 together with at least a 1-point decrease from baseline, and an endoscopic subscore of 0 or 1. The endoscopic subscore value of 1 does not include friability.

The Modified Mayo score combines stool frequency, rectal bleeding, and endoscopic subscores. Each subscore ranges from 0 to 3, and the combined score ranges from 0 to 9, with higher scores indicating greater severity. The remission definition therefore requires a low combined score as well as particular symptom and endoscopic findings; it is not simply a change in the total score.

A binary remission endpoint records whether each participant met the stated definition at the assessment time. Reporting the percentage makes the group-level frequency of that event understandable, while the confidence interval conveys uncertainty around the estimate. A week-12 endpoint provides a defined time point for comparing the randomized groups, but it does not describe the entire course of disease or establish how participants fared at every later assessment.

The registry uses the PCP Intent to Treat population for this outcome, defined as randomized participants who received at least one dose of PCP treatment. Why this endpoint was selected over other possible measures, and how missing week-12 assessments were handled, are not reported in the registry record.

7. Results Posted in the Registry

• PCP GB004 480 mg QD: 15.4% (12/78) versus 17.9% (14/78) on control; risk difference -2.6 percentage points (95% CI -14.3 to 9.1), risk ratio 0.86 (0.42–1.73); unadjusted two-proportion z-test p = 0.667.
• PCP GB004 480 mg BID: 22.5% (18/80) versus 17.9% (14/78) on control; risk difference 4.6 percentage points (95% CI -7.9 to 17.1), risk ratio 1.25 (0.67–2.34); unadjusted two-proportion z-test p = 0.477.

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.

Percentage of Participants With Clinical Response at PCP Week 12

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PCP GB004 480 mg QD: 34.6% (27/78) versus 42.3% (33/78) on control; risk difference -7.7 percentage points (95% CI -22.9 to 7.5), risk ratio 0.82 (0.55–1.22); unadjusted two-proportion z-test p = 0.323.
  • PCP GB004 480 mg BID: 52.5% (42/80) versus 42.3% (33/78) on control; risk difference 10.2 percentage points (95% CI -5.3 to 25.7), risk ratio 1.24 (0.89–1.73); unadjusted two-proportion z-test p = 0.200.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PCP GB004 480 mg QD 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 PCP GB004 480 mg BID and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Histologic Remission at PCP Week 12

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PCP GB004 480 mg QD: 26.5% (18/68) versus 26.1% (18/69) on control; risk difference 0.4 percentage points (95% CI -14.4 to 15.1), risk ratio 1.01 (0.58–1.78); unadjusted two-proportion z-test p = 0.959.
  • PCP GB004 480 mg BID: 32.9% (23/70) versus 26.1% (18/69) on control; risk difference 6.8 percentage points (95% CI -8.3 to 21.9), risk ratio 1.26 (0.75–2.12); unadjusted two-proportion z-test p = 0.381.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PCP GB004 480 mg QD 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 PCP GB004 480 mg BID and the control. The interval gives the range of effects that remain compatible with the data.

Percentage of Participants With Endoscopic Improvement at PCP Week 12

• Endpoint type: Binary: the percentage of participants with the event (counts rebuilt from the posted percentages and group sizes).
• Test: Unadjusted two-proportion z-test, with a Wald 95% confidence interval for the risk difference.
• Result:
  • PCP GB004 480 mg QD: 23.1% (18/78) versus 21.8% (17/78) on control; risk difference 1.3 percentage points (95% CI -11.8 to 14.4), risk ratio 1.06 (0.59–1.90); unadjusted two-proportion z-test p = 0.848.
  • PCP GB004 480 m BID: 30.0% (24/80) versus 21.8% (17/78) on control; risk difference 8.2 percentage points (95% CI -5.4 to 21.8), risk ratio 1.38 (0.80–2.36); unadjusted two-proportion z-test p = 0.239.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between PCP GB004 480 mg QD 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 PCP GB004 480 m BID and the control. The interval gives the range of effects that remain compatible with the data.

The posted secondary results cover clinical response, histologic remission, endoscopic improvement, and mucosal healing at PCP Week 12, along with clinical remission, clinical response, histologic remission, and endoscopic improvement at PCP Week 36. The registry lists 9 posted secondary outcomes. Across the week-12 outcomes with detailed results in the record, the observed group percentages vary by outcome and dose; the comparisons' confidence intervals generally leave substantial uncertainty. The overall pattern does not provide a consistently precise separation of either GB004 dose from placebo across the different measures.

These outcomes add context to the primary clinical remission result because they assess related but distinct clinical, tissue, and endoscopic features. They should not be treated as interchangeable measures: each uses its own definition, assessment, and analysis population. The histologic remission denominators, for example, differ from those for the primary endpoint, so the precision of that outcome is not directly comparable to the primary result without considering those denominators.

The secondary analyses are less conclusive when interpreted individually because multiple outcomes and comparisons create more opportunities for apparently notable findings to occur by chance. The registry record does not report a multiplicity adjustment or a prespecified hierarchy for these tests. Consequently, unadjusted secondary results carry less weight than a result supported by a clearly stated testing strategy that accounts for multiple comparisons.

The secondary outcomes can help describe the breadth of measurement, but they do not override the primary endpoint or resolve its uncertainty. The posted results do not establish a consistent pattern of effects across outcomes, and they should be interpreted as exploratory unless the registry record provides a stronger confirmatory framework. That framework is not reported in the registry record.

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

• Percentage of Participants With Clinical Response at PCP Week 12
• Percentage of Participants With Histologic Remission at PCP Week 12
• Percentage of Participants With Endoscopic Improvement at PCP Week 12
• Percentage of Participants With Mucosal Healing at PCP Week 12
• Percentage of Participants With Clinical Remission at PCP Week 36
• Percentage of Participants With Clinical Response at PCP Week 36
• Percentage of Participants With Histologic Remission at PCP Week 36
• Percentage of Participants With Endoscopic Improvement at PCP Week 36

9. Statistical Interpretation

10. Statistical Methods Explained

For a binary endpoint, each participant either meets the specified event definition or does not. The group percentage is the proportion meeting that definition at the assessment time. For the primary endpoint, the event is clinical remission at PCP Week 12 according to the registry's Modified Mayo definition. The percentage gives a direct description of how frequently remission was recorded in each study group, but it does not by itself quantify the uncertainty in a comparison.

What does a risk difference describe?

A risk difference compares the event proportions in two groups by subtracting one proportion from the other. It is expressed in percentage points when the proportions are expressed as percentages. A value of zero corresponds to equal proportions; a positive or negative value indicates which group had the higher observed proportion according to the comparison's ordering. The sign must be read with the stated group order in mind. A risk difference is an absolute contrast, unlike a relative measure such as a risk ratio.

The registry reports sponsor analyses using the Cochran-Mantel-Haenszel method and labels their parameter as Risk Difference (RD). This method is used to estimate a comparison across strata when stratification is part of the analysis. The registry record does not report the stratification details or enough of the analysis plan to explain precisely how the strata were defined. The method label should therefore be reported without inferring unlisted adjustments.

How should the p-value be understood?

A p-value describes how incompatible the observed data are with a specified null hypothesis under the statistical model used. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of a difference. The sponsor-reported primary comparison p-values are 0.669 for once-daily GB004 versus placebo and 0.472 for twice-daily GB004 versus placebo. Read alongside the confidence intervals, these results do not provide a precise estimate that excludes no difference.

The registry also includes unadjusted recalculations from posted summary statistics. Those calculations do not reproduce every potential feature of the sponsor's analysis, such as stratification or handling of missing outcomes. They are useful as a transparent, simple comparison of the reported group summaries, but the sponsor's own analysis takes precedence for the trial's official inference. The record does not flag a discrepancy for these results.

Why does over-dispersion matter?

Over-dispersion is a general statistical concern that arises when observed variation is greater than a model expects. It can affect uncertainty estimates if a model assumes less variation than the data contain. This primary outcome is a binary percentage, and the registry lists confidence intervals; it does not report over-dispersion as an issue or describe a model-based dispersion adjustment. This general concept should not be taken as a claim about the analysis of this trial.

In general, a confidence interval represents uncertainty around an estimate under the assumptions of the analysis. It is not a guarantee that the true value lies within the interval, and it does not give the probability that a particular treatment effect is true. The interval's width helps indicate precision: a wider interval leaves more plausible values unresolved. For a difference, an interval spanning zero is compatible with no difference as well as with differences on either side.

The registry's primary endpoint definition and analysis population are stated, but the details of the statistical analysis plan, missing-data methods, multiplicity strategy, and original design assumptions are not reported in the registry record. Those omissions limit how completely the reported tests can be reconstructed or interpreted.

11. Confidence Intervals and Precision

The primary outcome estimates have 95% confidence intervals. For placebo, the remission percentage was 17.9% with an interval from 11.0% to 27.9%. For GB004 480 mg once daily, it was 15.4% with an interval from 9.0% to 25.0%. For GB004 480 mg twice daily, it was 22.5% with an interval from 14.7% to 32.8%. The intervals show that each observed percentage is estimated with uncertainty rather than known exactly.

For the sponsor-reported contrasts, the 95% interval for once-daily GB004 versus placebo runs from -15.2 to 10.2 percentage points. The interval for twice-daily GB004 versus placebo runs from -9.0 to 17.8 percentage points. Both span zero, so the results are compatible with no difference and with effects in either direction. The intervals also leave room for differences that may be larger than the point estimates.

Precision concerns how narrowly the data locate an estimate. It is not the same as whether a result is important, nor is a narrow interval automatically evidence of an important effect. Here, the intervals around the risk differences are broad enough that the direction and size of any underlying difference remain uncertain. The p-values do not remove this uncertainty.

Confidence intervals depend on the analysis and its assumptions. The registry identifies the sponsor method as Cochran-Mantel-Haenszel, but does not report all the details required to assess every assumption or reproduce the calculation. The endpoint-specific denominators also vary across outcomes, so precision should be considered for each outcome on its own rather than assumed to be identical throughout the study.

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 illustrative calculations based on the observed effect, not a report of the trial's original design calculation. For the binary outcomes in this study, the figures refer to participants per arm, not total participants and not total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set as the stated fraction of the observed effect.

The 80% power column describes the planned number of participants per arm under which a study would have an 80% chance of detecting the specified effect, if that effect and the calculation assumptions were correct. The 90% power column describes the corresponding planning target for a 90% chance. These are design illustrations, not guarantees about a future study's result. The figures are not observed power.

Rows that plan for 100%, 75%, or 50% of the observed effect represent different assumed effect sizes. A smaller effect is harder to distinguish from random variation, so planning to detect a smaller effect requires more participants. When the observed effect is close to zero, planning calculations based on a fraction of that effect can become extremely large and unstable as practical guidance. The registry record does not report the original target effect, sample-size justification, or design assumptions used for this trial.

The posted figures should therefore be read as conditional illustrations tied to the observed contrast and stated assumptions, not as evidence that the study had adequate or inadequate power. They do not determine whether the observed result is true, clinically meaningful, or likely to recur.

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, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.179; treatment proportion p₁ = 0.154; average p̄ = 0.167.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.5270 = 1.0330.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5267 = 0.4433.
4. n = (1.0330 + 0.4433)² / (-0.0256)² = 3,315.0, rounded up to 3,315 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
p0 <- 0.179487179487179                          # control proportion
p1 <- 0.153846153846154                          # treatment proportion
n_per_arm <- function(power, frac = 1) {
  q1 <- p0 + (p1 - p0) * frac               # smaller effect = fraction of the observed difference
  pbar <- (p0 + q1) / 2
  z_b <- qnorm(power)
  ceiling(round((z_a * sqrt(2 * pbar * (1 - pbar)) + z_b * sqrt(p0 * (1 - p0) + q1 * (1 - q1)))^2 / (q1 - p0)^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 (unrounded n per arm)
cat("power.prop.test:", round(power.prop.test(p1 = p0, p2 = p1, power = 0.80)$n, 1), "\n")

# Simulation: how often does the z-test reject at the 80%-power sample size?
set.seed(4556383)
n    <- n_per_arm(0.80)
reps <- 20000
x0 <- rbinom(reps, n, p0); x1 <- rbinom(reps, n, p1)
ph <- (x0 + x1) / (2 * n)
z  <- ((x1 - x0) / n) / sqrt(ph * (1 - ph) * 2 / n)
cat(sprintf("Simulated power at n = %s per arm: %.3f (%d replicates)\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE), reps))

Output from running the code

100% of observed effect: n per arm = 3,315 (80% power), 4,438 (90% power)
 75% of observed effect: n per arm = 5,985 (80% power), 8,012 (90% power)
 50% of observed effect: n per arm = 13,668 (80% power), 18,297 (90% power)
power.prop.test: 3315 
Simulated power at n = 3,315 per arm: 0.800 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-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's posted primary comparisons use the Cochran-Mantel-Haenszel method and report risk differences with 95% confidence intervals. For once-daily GB004 versus placebo, the estimate is -2.6 percentage points, with an interval from -15.2 to 10.2. For twice-daily GB004 versus placebo, the estimate is 4.6 percentage points, with an interval from -9.0 to 17.8. Both intervals include zero and allow values on either side of no difference.

The registry also includes simple unadjusted recalculations from the posted summary statistics. Such recalculations can be useful for understanding the basic contrast in observed proportions, but may not match the sponsor analysis because they use a simpler calculation and may not incorporate its analytical structure. The sponsor's own analysis takes precedence for the official trial comparison. The registry does not flag a discrepancy between the recalculations and reported analysis.

The sponsor-reported p-values for the primary comparisons are 0.669 and 0.472. These values should be read together with the effect estimates and intervals, not as standalone measures of evidence or importance. The record does not report enough detail to reconstruct all elements of the sponsor's analysis plan.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and multiple secondary outcomes, with 20 analyses overall. Testing several outcomes and dose comparisons raises the general issue of multiplicity: as the number of statistical tests increases, the chance of at least one apparently unusual result can increase even when there is no corresponding underlying effect. This is why secondary p-values should not be treated as if each were the only planned test.

The registry record does not report a multiplicity adjustment, a gatekeeping procedure, or a prespecified hierarchy for the secondary outcomes. It also does not report whether analyses were designated confirmatory or exploratory. Without that information, the secondary findings should be interpreted cautiously, and isolated p-values should not be taken as conclusive evidence.

The primary analysis population is defined as randomized participants who received at least one dose of PCP treatment. The registry does not report how missing week-12 endpoint data were handled, whether participants with missing assessments were counted as nonresponders, or whether sensitivity analyses were performed. It also does not provide enough information to assess the effect of missing data on the estimates. Missing outcomes can affect both the event percentages and the comparison when their occurrence is related to treatment assignment or outcome status.

Although the primary endpoint description names the analysis population, the record does not state whether all other analyses used the same population or how analysis populations were specified for each secondary endpoint. Some secondary denominators differ, but the reasons for those differences are not reported in the registry record. This prevents a complete assessment of population consistency across endpoints.

The sponsor's analysis method is identified as Cochran-Mantel-Haenszel, but details of the stratification and statistical plan are not reported. The original sample-size assumptions, interim-analysis plans, and handling of protocol deviations are likewise not reported in the registry record. These gaps limit independent evaluation of the full analysis strategy.

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 (3.1%), anaemia (1.3%), cholecystitis (1.2%), anal abscess (1.2%), prostate cancer (1.2%).

For the placebo-controlled period, the registry reports serious adverse events in 2 participants in the placebo group, 2 in the GB004 480 mg once-daily group, and 4 in the GB004 480 mg twice-daily group. The corresponding numbers at risk for these summaries were 78, 76, and 82. The record also lists 13, 29, and 27 participants with other adverse events, respectively, using the stated group-specific numbers at risk.

For the open-label extension, the registry reports 9 participants with serious adverse events and 8 with other adverse events, among 130 at risk; it reports 1 death. The extension was open label and used GB004 480 mg twice daily, so these figures should be kept distinct from the randomized placebo-controlled comparisons.

Serious adverse events and other adverse events are different summary categories. These counts describe events recorded in the registry; they do not establish that treatment caused an event. The record lists serious terms including ulcerative colitis, anaemia, cholecystitis, anal abscess, prostate cancer, and urinary calculus, with the corresponding percentages stated in the registry. These summaries alone do not provide event timing, duration, severity details beyond the category, or a comparative causal assessment. The registry record does not report a detailed safety analysis plan.

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

The primary endpoint results describe the observed proportion meeting the registry's clinical remission definition at PCP Week 12. The sponsor-reported comparisons have confidence intervals that include no difference and values in both directions. The estimates therefore remain uncertain: they do not precisely establish the size or direction of a difference between either GB004 regimen and placebo on this endpoint.

This does not mean the groups were identical. A confidence interval that includes zero does not prove equality; it indicates that the observed data and analysis do not rule out no difference, while also permitting differences in either direction. Conversely, a higher observed percentage in one group does not by itself demonstrate a reliable treatment effect. The point estimates, intervals, and analysis method must be considered together.

The findings concern one endpoint at one assessment time in the stated PCP population. They do not by themselves settle the results for the week-36 endpoints, the open-label extension, all secondary outcomes, or safety. They also do not explain why the study was terminated. The registry record does not report the reason for termination or the original assumptions used to design the trial.

The safety counts are descriptive summaries, not proof that an event was caused by a study treatment or that an event did not occur when no count is listed. Likewise, the secondary outcomes add information about different measures but are subject to uncertainty and multiplicity considerations.

Statistical evidence and clinical importance are related but distinct. The registry record does not provide a threshold for a clinically important difference on the primary endpoint. The posted estimates should therefore be described in terms of their observed values and uncertainty, without asserting that GB004 works or does not work. They do not establish a recommendation for care or predict an individual participant's outcome.

18. Why This Trial Matters Statistically

This trial is statistically informative because it compares two dose regimens with placebo in a randomized, masked, parallel-group Phase 2 design and defines a specific week-12 endpoint. Reporting the group percentages, risk differences, confidence intervals, and sponsor analyses allows readers to distinguish the observed event rates from the uncertainty around comparative effects.

The results also illustrate why a point estimate alone is not enough. The once-daily and twice-daily groups had different observed remission percentages relative to placebo, but the reported intervals for both comparisons span zero and extend in both directions. That range of plausible effects matters more than treating the observed percentages as fixed truths.

The registry includes multiple secondary outcomes and analyses, making multiplicity and the prespecification of analyses important to interpretation. It also includes a separate open-label extension, which cannot be read as a blinded randomized comparison with placebo. Keeping these design features distinct prevents claims from extending beyond what the results directly address.

Finally, the study status is terminated, yet the reason is not reported in the registry record. That is important context for readers, but it does not permit a statistical explanation of the termination. Missing details about the analysis plan, sample-size justification, and missing-data handling also limit how completely the results can be independently assessed.

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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Interpretation is limited by details that are not reported in the registry record. The reason for study termination is not stated. The original sample-size justification, target effect, statistical analysis plan, interim-analysis arrangements, multiplicity strategy, and missing-data methods are also not reported. These omissions make it difficult to assess whether the analyses followed a prespecified plan or how incomplete endpoint data may have affected the estimates.

The primary analysis population is defined as randomized participants who received at least one PCP treatment dose, but the record does not explain the handling of participants who did not receive treatment or the reasons for differences in outcome denominators. Endpoint-specific denominators vary, notably for histologic remission. The record does not give enough information to determine how missing assessments or eligibility for each outcome influenced those denominators.

The study includes a 24-week open-label extension, but those observations are not equivalent to the randomized placebo-controlled comparison. The safety summaries combine counts by treatment period and do not establish causation. Detailed event timing and a full comparative safety interpretation are not reported in the registry record.

The primary comparison intervals are broad and include zero, leaving uncertainty about the direction and magnitude of any difference. The study is Phase 2, and the record does not establish that it was designed to give definitive answers for every endpoint. These limitations do not invalidate the posted results, but they constrain the strength and scope of conclusions that can be drawn from them.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: A Study With GB004 in Adult Subjects With Active Ulcerative Colitis (UC) — NCT04556383.
• Registry record last updated 2023-08-01; status last verified 2023-07.
• Results first posted 2023-08-01.
• 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

The registry describes NCT04556383 as a randomized, double-blind, placebo-controlled, multicenter Phase 2 study of GB004 in adults with mild-to-moderate active ulcerative colitis. The design included a 36-week placebo-controlled period and a 24-week open-label extension, with GB004 480 mg once daily and twice daily evaluated against placebo during the PCP. The registry reports enrollment of 236 and lists the study status as terminated.

The primary endpoint was clinical remission at PCP Week 12 in the PCP Intent to Treat population. The observed percentages were 17.9% for placebo, 15.4% for once-daily GB004, and 22.5% for twice-daily GB004. The sponsor-reported risk-difference intervals for both comparisons included zero and extended in both directions, leaving substantial uncertainty about comparative effects.

The registry also reports secondary outcomes and adverse-event summaries. The reason for termination, original design assumptions, analysis plan, multiplicity strategy, and missing-data methods are not reported in the registry record.