Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease (NCT00792740), a randomized phase 1, phase 2 study. The primary outcome is Number of Patients Achieving Complete Healing of Mucosal Ulcerations of Ileum and/or Colon.

2. Clinical Question

The trial asked whether complete healing, assessed by endoscopy, occurred among participants receiving ITF2357 compared with those receiving placebo. The endpoint concerned disappearance of mucosal ulceration, not a change in symptoms alone. The study also listed endoscopic measures of disease activity, clinical activity measured with the Crohn’s Disease Activity Index, safety and tolerability, and pharmacokinetics as secondary objectives.

The posted primary counts were one participant in the ITF2357 group and none in the placebo group. The estimated risk difference was 0.04, with an unadjusted p-value of 0.303. These figures describe the posted observations and an unadjusted comparison; they do not establish that the groups differed. The confidence interval is wide and includes values on either side of no difference, so the result is compatible with a range of effects.

3. Trial Design

The registry describes a randomized, double-blind, parallel-group, placebo-controlled study in phase 1 and phase 2. The listed enrollment was 51. The posted outcome data include a placebo group with 26 participants and an ITF2357 group with 25. The record identifies Italfarmaco as sponsor and Crohn’s disease as the condition studied.

Participants assigned to ITF2357 received oral ITF2357 50 mg twice daily; those assigned to placebo received matching oral capsules twice daily. The primary outcome was assessed at week 8. The stated treatment objective was administration for 8 consecutive weeks. The registry lists study status as terminated. A reason for termination is not reported in the registry record, and the record does not establish whether termination affected collection or reporting of any particular outcome.

Random allocation and double masking are features intended, in general, to reduce systematic differences in treatment assignment and expectations during assessment. A placebo comparator permits the observed outcome in the active-treatment group to be considered alongside the outcome under the comparator, within the setting and population studied. The registry record does not report the method used to generate the allocation sequence, allocation concealment procedures, or the details of how masking was maintained.

The primary analysis population is described as ITT, with a specific definition: randomized patients who took at least one dose of study treatment. The record does not report a participant flow account or group-specific details about exclusions, withdrawals, or missing endpoint assessments. Those omissions limit assessment of how the stated population definition was applied in practice.

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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: ITT: population included all randomized patients who took at least one dose of 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.

Population: ITT: All randomized patients who received at least one treatment with study medication

6. Primary Endpoint

The registry lists the primary outcome as Number of Patients Achieving Complete Healing of Mucosal Ulcerations of Ileum and/or Colon, measured over At week 8.

The primary endpoint counts participants who achieved complete healing of mucosal ulcerations in the ileum and/or colon, assessed by endoscopy at week 8. The registry description defines complete healing as disappearance of mucosal ulceration. It reports the outcome as a participant count in the stated ITT population, rather than as a continuous endoscopic score.

An endoscopic endpoint is used to assess visible mucosal disease directly. This addresses a different aspect of Crohn’s disease from clinical activity measured through symptoms or a clinical index. The registry also lists changes in the Crohn’s Disease Endoscopic Index of Severity and the Simple Endoscopic Score for Crohn’s Disease, along with clinical activity and safety measures, as secondary outcomes. The primary endpoint is more stringent in form than a general change in a score: it asks whether complete healing was achieved.

In the posted results, one participant receiving ITF2357 and no participants receiving placebo achieved complete healing. A count endpoint is readily interpretable, but sparse event counts can make a group comparison imprecise. The observed counts alone do not establish a reliable difference between treatments. Interpretation therefore depends not only on the direction of the estimated difference but also on its confidence interval, the uncertainty reflected in the unadjusted test, and the completeness of outcome reporting.

7. Results Posted in the Registry

• ITF2357: 4.0% (1/25) versus 0.0% (0/26) on control; risk difference 4.0 percentage points (95% CI -3.7 to 11.7); unadjusted two-proportion z-test p = 0.303.

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 Patients Achieving Full Endoscopic Remission ( Based on CDEIS Score)

• 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:
  • ITF2357: 4.0% (1/25) versus 7.7% (2/26) on control; risk difference -3.7 percentage points (95% CI -16.5 to 9.1), risk ratio 0.52 (0.05–5.38); unadjusted two-proportion z-test p = 0.575.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ITF2357 and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients Achieving Endoscopic Remission (Based on CDEIS Score)

• 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:
  • ITF2357: 20.0% (5/25) versus 11.5% (3/26) on control; risk difference 8.5 percentage points (95% CI -11.5 to 28.4), risk ratio 1.73 (0.46–6.50); unadjusted two-proportion z-test p = 0.406.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ITF2357 and the control. The interval gives the range of effects that remain compatible with the data.

Number of Patients Achieving Endoscopic Response (Based on CDEIS Score)

• 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:
  • ITF2357: 28.0% (7/25) versus 23.1% (6/26) on control; risk difference 4.9 percentage points (95% CI -19.0 to 28.8), risk ratio 1.21 (0.47–3.11); unadjusted two-proportion z-test p = 0.687.
• Interpretation:
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ITF2357 and the control. The interval gives the range of effects that remain compatible with the data.

Across the posted secondary outcomes, the overall pattern is mixed rather than consistently favoring one group. The secondary endoscopic measures include outcomes based on remission, response, and changes in endoscopic scores; the clinical outcomes concern CDAI activity. These measures address related but not identical aspects of disease activity, so variation among them is possible and does not by itself demonstrate a contradiction.

The primary endpoint asks about complete healing, a specific and stringent binary outcome. Secondary outcomes can offer supporting context by examining other definitions of endoscopic status or clinical activity, but they do not answer the same question. In this record, the secondary findings do not provide a uniformly clear pattern that would resolve the uncertainty in the primary comparison. Their estimates should be considered alongside their own uncertainty and the limited information available for the primary endpoint.

Unadjusted secondary results carry less weight when several outcomes are examined. In general, making multiple comparisons increases the opportunity for apparently notable findings to arise without a corresponding underlying effect. Statistical adjustment or a prespecified hierarchy can address some of this concern, but the registry record does not report a multiplicity strategy or adjusted analyses. The posted analyses list is empty.

The secondary comparisons are therefore descriptive and exploratory in this record. They may help identify questions for further study, but they should not be treated as independent confirmation of efficacy. A directionally favorable result on an individual secondary measure would not overturn the imprecision of the primary result, and a directionally unfavorable result would not establish harm. No sponsor-reported interpretation of the secondary outcomes is reported in the registry record.

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

• Number of Patients Achieving Full Endoscopic Remission ( Based on CDEIS Score)
• Number of Patients Achieving Endoscopic Remission (Based on CDEIS Score)
• Number of Patients Achieving Endoscopic Response (Based on CDEIS Score)
• The Mean Changes of Crohn's Disease Endoscopic Index of Severity (CDEIS) From Baseline to Week 8
• The Mean Changes of Simple Endoscopic Score for Crohn Disease (SES-CD) From Baseline to Week 8
• The Mean Changes of CDAI Score From Baseline to Week 4-8-follow up
• Number of Patients Achieving Remission (Based on CDAI Score)
• Number of Patients Achieving Response (Based on CDAI Score)

9. Statistical Interpretation

10. Statistical Methods Explained

What does the risk difference describe?

For a binary endpoint, each participant is classified according to whether the event occurred. Here the event is complete endoscopic healing by week 8. The risk difference compares the event proportion in the ITF2357 group with the event proportion in the placebo group, with the direction expressed as ITF2357 minus placebo. A positive value therefore indicates a higher observed event proportion in the ITF2357 group; a negative value indicates a higher observed event proportion in the placebo group.

The primary risk difference is 0.04. This is a point estimate: one estimate based on the observed counts, not a known value for the underlying treatment effect. It should not be interpreted without considering its uncertainty. Because the event counts are sparse, the estimate is particularly sensitive to the small number of observed events.

How should the p-value be read?

The unadjusted p-value for the primary comparison is 0.303. In general, a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be under the assumptions of the statistical test. It is not the probability that the null hypothesis is true, and it is not the probability that the result occurred “by chance.” It also does not measure the size or clinical importance of an effect.

The p-value is unadjusted. The registry record does not report the sponsor’s statistical analysis or a multiplicity adjustment for the primary comparison. The p-value should therefore be understood as an unadjusted comparison of the posted summary statistics, not as a documented sponsor-reported confirmatory analysis.

What does a confidence interval add?

A confidence interval gives a range of effect values compatible with the observed data under the method’s assumptions. In repeated use, a confidence-interval procedure with a stated confidence level has a defined long-run coverage property. It does not assign a probability to the fixed true effect after the data have been observed.

For the primary risk difference, the interval crosses zero. Zero represents no difference in event proportions. The interval’s position on both sides of zero indicates that the posted data do not distinguish confidently between no difference and effects in either direction. Its breadth communicates limited precision; the point estimate alone would obscure that uncertainty.

Why do sparse binary outcomes matter?

When an outcome is a count of participants with an event, the information available for comparing groups depends strongly on how many events occur. In this trial, the primary outcome occurred only once across the reported groups. With so few events, estimates can vary substantially with small changes in the observed counts. Standard approximations can also be less dependable when event counts are sparse, depending on the method used.

The registry record does not report the statistical test or interval-construction method used by a sponsor. The posted comparison is therefore useful as an unadjusted summary-based calculation, but it should not be mistaken for a fully documented analysis plan. The record does not provide model diagnostics, covariate adjustment details, or sensitivity analyses.

What do the planning illustrations mean?

Planning illustrations are included for some secondary binary outcomes. They use the observed effect, or a stated fraction of it, under assumptions of a two-sided significance level of 0.05, equal allocation between groups, and a normal approximation. The resulting values are participants per arm for 80% power or participants per arm for 90% power under those assumptions.

These figures are planning illustrations, not observed power and not the trial’s reported sample-size justification. They describe hypothetical future designs calibrated to effects estimated from the posted data. Because the observed effects in a small study can be unstable, planning directly from them can produce unstable sample-size estimates as well. The registry does not report that these assumptions were used to design the study. A sample-size justification for the actual trial is not reported in the registry record.

The registry lists 13 outcome measures and 12 posted secondary outcomes, while the reported analyses list is empty. The secondary outcome results can be described, but the record does not provide a complete statistical analysis plan explaining how outcomes were prioritized, how missing observations were handled, or whether any interim analyses were conducted. Those methodological details cannot be inferred from the posted counts or p-values.

11. Confidence Intervals and Precision

The primary point estimate is a risk difference of 0.04. Its confidence interval crosses zero and extends to both positive and negative values. This is the key precision finding: the posted data leave considerable uncertainty about the direction and size of the underlying difference. The interval does not support a precise estimate of a treatment effect.

The event counts are one participant with complete healing in the ITF2357 group and none in the placebo group. Since only one event was observed, the estimate is based on sparse information. A confidence interval is especially important in this setting because the point estimate can appear more decisive than the underlying evidence warrants. The unadjusted p-value of 0.303 is consistent with the broad uncertainty reflected in the interval, but it should not be treated as a substitute for the interval or as a measure of effect size.

In general, a confidence interval describes the range of values reasonably compatible with the data under the chosen method and its assumptions. A wide interval signals low precision; it does not prove that the true effect is large, small, or absent. Because the registry record does not describe the interval method, the calculation should be read as a summary-based estimate rather than as a documented sponsor analysis.

The posted summaries do not resolve whether a modest benefit, no difference, or an effect in the opposite direction is most plausible. More precise estimation would require evidence with greater information about the endpoint. The existing result should not be converted into a claim of equivalence or into a claim of benefit based only on the direction of its point estimate.

12. Multiplicity, Missing Data and Analysis Populations

The registry identifies a primary outcome and lists multiple secondary outcomes, including measures of endoscopic remission and response, changes in endoscopic scores, and clinical activity. It reports 13 outcome measures and 12 posted secondary outcomes. The reported analyses list is empty. The registry record does not report a statistical analysis plan describing an outcome hierarchy, adjustment for multiple comparisons, or rules for selecting among analyses.

Multiplicity matters because repeated testing across outcomes can increase the chance that at least one comparison appears noteworthy even when none reflects a reliable underlying effect. This general concern does not mean that a particular secondary result is false. It means that unadjusted secondary p-values require caution and should not be interpreted as if each were the sole planned test. The record does not establish whether any multiplicity control was used outside the information posted.

The record defines the primary population as randomized participants who took at least one dose of study treatment. This is the registry’s stated ITT definition. The record does not report a participant flow account, the number of participants with missing primary assessments, reasons for missingness, or an imputation or sensitivity-analysis approach. It is therefore not possible to assess from the posted information whether missing endpoint data affected the comparison.

The record also does not report interim analyses, stopping rules, or a sample-size justification for the actual trial. Although planning illustrations are available for some secondary outcomes, they are not evidence of the trial’s original design assumptions. The study status is terminated, but a reason for termination and its relationship to analysis or follow-up are not reported in the registry record. These omissions limit assessment of how the reported results relate to the complete intended analysis.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: crohn's disease (12.0%), back pain (3.8%).

The posted serious adverse event summaries list 2 affected participants in the placebo group and 3 in the ITF2357 group. The groups at risk are reported as 26 and 25, respectively. No deaths are reported in either group. The listed serious-event terms include Crohn’s Disease, reported as 12.0%, and Back Pain, reported as 3.8%.

These figures describe events recorded during the study; they do not establish that treatment caused an event or that the groups differ in safety. Serious adverse events are distinct from the broader category of other adverse events, for which the record reports 17 affected participants in the placebo group and 20 in the ITF2357 group. The registry does not provide enough information to determine event timing, duration, severity beyond the serious-event classification, or relatedness assessments.

With a small study and limited event counts, comparative safety estimates would be imprecise. The absence of deaths in the posted data does not establish that no risk exists, and the observed serious-event counts should not be used alone to make a treatment decision. The registry record’s safety figures are descriptive and should be interpreted within these limits.

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

The posted primary result says that complete endoscopic healing at week 8 was recorded for one participant receiving ITF2357 and none receiving placebo. The estimated risk difference is 0.04, and the unadjusted p-value is 0.303. The confidence interval includes no difference and extends in both directions. Together, these statistics describe a small observed difference with substantial uncertainty.

The result does not establish that ITF2357 caused complete healing, nor does it establish that the treatment has no effect. A non-significant unadjusted comparison is not proof of equivalence. The limited number of observed events means that the data do not precisely identify the underlying difference between groups. The interpretation should remain tied to this particular endpoint, population, comparator, and follow-up time.

The study also recorded secondary outcomes, but those results do not provide a consistent pattern that removes the primary uncertainty. The registry record does not report a multiplicity plan, sponsor-reported analyses, or enough information about missing outcome data to fully assess the analysis. The study is listed as terminated, with no reason reported in the registry record.

These results are not a recommendation for or against treatment. They are a statistical description of the information posted in the registry. The findings can be used to understand what was observed and how imprecisely it was estimated, but they do not support a definitive claim about benefit, lack of benefit, or comparative safety.

15. Why This Trial Matters Statistically

This study illustrates why event counts and uncertainty matter when interpreting a binary clinical endpoint. Complete mucosal healing is a clear clinical concept in the registry description, but the posted primary outcome occurred only once across the two groups. A point estimate can be calculated from such data, yet its precision remains limited. Reporting the estimate together with its confidence interval and observed counts prevents the direction of the point estimate from being mistaken for a settled conclusion.

The trial also illustrates the distinction between a primary endpoint and a collection of secondary outcomes. Endoscopic and clinical measures can provide useful complementary perspectives, but multiple unadjusted comparisons do not automatically amount to multiple independent confirmations. Without a reported analysis plan or multiplicity approach, the secondary findings are best viewed as exploratory context.

For clinical researchers and biostatisticians, the record highlights the value of transparent reporting about the analysis population, missing observations, sample-size rationale, and analysis procedures. The registry defines the primary population but does not report participant flow, missing-data handling, or sponsor analyses. These details matter for judging how closely the posted comparison reflects the intended study question.

The result is therefore statistically informative chiefly as a demonstration of limited precision: the data yield a risk-difference estimate, but leave a broad range of effects compatible with the observations. That distinction is important when interpreting small trials and when considering what further evidence would need to clarify.

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.

The primary endpoint has very sparse event data: one participant in the ITF2357 group and none in the placebo group achieved complete healing. This limits precision and makes the estimate sensitive to small changes in the observed counts. The confidence interval crosses zero, so the data do not clearly distinguish a difference from no difference.

The registry record does not report the statistical analysis plan, the method used to calculate the primary interval, or a sponsor-reported analysis. It also does not report a sample-size justification for the actual study. While planning illustrations appear for some secondary outcomes, they are not the trial’s documented design calculations and should not be treated as evidence of observed power.

The primary population is defined as randomized participants who took at least one dose, but the record does not report participant flow, missing primary assessments, reasons for missing data, or missing-data methods. It is not possible to assess whether missingness or exclusions influenced the posted outcome counts.

The study is listed as terminated, but the reason and consequences of termination are not reported in the registry record. The primary outcome is assessed at week 8, and the posted information does not establish longer-term outcomes. Secondary results are also subject to uncertainty, and no multiplicity strategy is reported. These limitations constrain interpretation of both efficacy and safety comparisons.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: Effect of ITF2357 on Mucosal Healing in Patients With Moderate-to-severe Active Crohn's Disease — NCT00792740.
• Registry record last updated 2023-07-19; status last verified 2022-01.
• Results first posted 2023-07-19.
• 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

The registry describes a randomized, double-blind, parallel-group, placebo-controlled phase 1 and phase 2 study of oral ITF2357 in moderate-to-severe active Crohn’s disease. The listed enrollment is 51, and the study status is terminated.

The primary outcome was complete endoscopic healing of mucosal ulcerations in the ileum and/or colon at week 8. The posted count was one participant in the ITF2357 group and none in the placebo group. The estimated risk difference was 0.04, with an unadjusted p-value of 0.303; the confidence interval includes zero and indicates substantial uncertainty.

The record lists secondary endoscopic and clinical outcomes, but the overall pattern is mixed. It does not report sponsor analyses, a multiplicity plan, missing-data methods, or a reason for termination. The primary result is best understood as an imprecise comparison, not as evidence establishing benefit, no effect, or equivalence.