An Open-label Study of Vedolizumab (MLN0002) in Participants With Ulcerative Colitis and Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-label Study of Vedolizumab (MLN0002) in Participants With Ulcerative Colitis and Crohn's Disease (NCT00790933), a na phase 3 study. The primary outcome is Percentage of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs).

2. Clinical Question

The study focused on safety during chronic vedolizumab administration in participants with ulcerative colitis and Crohn's disease. Its primary endpoint concerned events that began after study drug exposure and serious events meeting specified clinical criteria. The follow-up window ran from the first dose in this study through 16 weeks after the last dose, for up to approximately 8.5 years.

This is a descriptive safety question, not a comparison of vedolizumab with another treatment or with no treatment. Because there is no control group, the results describe events recorded among the participants followed in this study; they do not by themselves establish how often those events would have occurred without vedolizumab. The open-label design also means participants and study personnel were not masked to treatment assignment.

3. Trial Design

This was a Phase 3, completed, multicenter, open-label study of vedolizumab in participants with ulcerative colitis and Crohn's disease. The recorded enrollment was 2243. The study began on 2009-05-22, and its primary completion date was 2017-10-31. The intervention was vedolizumab 300 mg by 30-minute intravenous infusion every 4 weeks, starting at Week 0, for approximately up to 510 weeks.

The trial is recorded as single-group, with no masking and allocation listed as not applicable. It therefore has no randomized comparator arm. Its stated purpose was to collect data on important clinical safety events associated with chronic vedolizumab administration. The primary endpoint was the percentage of participants with one or more treatment-emergent adverse events and serious adverse events. The endpoint follow-up period extended from first dose in this study to 16 weeks after the last dose, up to approximately 8.5 years.

The endpoint's safety population is defined using participation across Studies C13004, C13006, C13007, and C13011, together with receipt of any amount of vedolizumab in Study C13008. De novo participants who received any amount of vedolizumab in Study C13008 were also included. This definition matters when interpreting the recorded denominator: the safety population is not described only by the enrollment figure for the study record.

The registry record does not report a separate control group, masking procedures, or an allocation process. It also does not report the study's sample-size justification or detailed statistical analysis plan. Those details should not be inferred from the Phase 3 label or from the length of follow-up.

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: Participants with a diagnosis of ulcerative colitis and Crohn's disease who participated in previous studies: C13004 (NCT00619489), C13006 (NCT00783718), C13007 (NCT00783692) and C13011 (NCT01224171) and DeNovo participants were enrolled into 1 treatment group, vedolizumab 300 mg, 30-minute intravenous (IV) infusion, every 4 weeks (Q4W).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The safety population was defined as all participants who participated in Studies C13004, C13006, C13007, and C13011 and received any amount of vedolizumab in Study C13008. De novo participants who received any amount of vedolizumab in Study C13008 were also included in the safety population.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Safety population was defined as all participants who received any amount of vedolizumab in this study.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With One or More Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs), measured over From first dose of study drug in this study through 16 weeks after the last dose of study drug (Up to approximately 8.5 years).

The primary endpoint is the percentage of participants with one or more treatment-emergent adverse events (TEAEs) and serious adverse events (SAEs). A treatment-emergent adverse event is an untoward medical occurrence with onset after the participant received study drug. The definition does not require the event to be judged caused by the drug. An event can include an unfavorable sign, symptom, clinically significant laboratory finding, or disease temporally associated with drug use.

An SAE is an event that results in death, is life-threatening, requires inpatient hospitalization or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is medically significant. These criteria identify events with serious consequences or clinical significance, rather than events defined by a suspected causal link to treatment.

In general, safety endpoints of this kind are used to describe the occurrence of unwanted medical events during exposure and follow-up. They help characterize what was observed in the enrolled safety population. They do not, by themselves, distinguish events caused by treatment from events associated with the underlying conditions or other circumstances. The registry record states the endpoint and event definitions, but a primary estimate with a confidence interval is not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a single-group, open-label study. That design determines the scope of statistical interpretation. With no comparator arm, analyses can describe how many participants experienced events during observation, but they cannot directly estimate a difference between vedolizumab and another treatment. Open-label status means treatment was not masked. The registry record does not report further methods for reducing the effect of knowledge of treatment on event assessment.

What does a participant-level event percentage represent?

In general, a participant-level percentage expresses the share of an at-risk group that experienced a defined event or outcome. For a safety endpoint worded as one or more events, each participant is counted as affected if the endpoint definition is met, regardless of how many qualifying events that participant experienced. That differs from an event count, which may include repeated events from an individual. The primary endpoint is described as a percentage of participants, while the adverse-event summary also lists affected and at-risk counts.

The record gives counts of 825 affected among 2243 at risk for serious adverse events and 1820 affected among 2243 at risk for the other adverse-event grouping. It does not report a confidence interval for these counts or an inferential comparison. A recalculated percentage or interval is not reported in the registry record and is not necessary to interpret the posted counts.

Why does the absence of a comparator matter?

In general, a comparison group helps account for event occurrence that might have happened even without the intervention under study. In a single-group study, observed events can reflect the underlying disease, other health circumstances, treatment exposure, or combinations of these factors. The registry data do not separate those explanations. The trial's descriptive safety purpose is consistent with reporting events during exposure, but it does not by itself establish causation.

Because the study includes participants with both ulcerative colitis and Crohn's disease, a pooled safety summary may include events in people with different underlying conditions. The record lists both conditions and defines a safety population that includes participants from multiple studies. It does not provide subgroup-specific primary endpoint results in the information, so differences by diagnosis or participant history cannot be evaluated from these results.

What can confidence intervals and tests add?

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical model and sampling process. Its width conveys statistical precision, not whether an event is clinically important or caused by treatment. A hypothesis test addresses a defined statistical comparison and depends on the analysis plan and assumptions. Neither a confidence interval nor a test can replace a suitable comparator when the question is whether treatment changes event risk relative to an alternative.

No confidence intervals, p-values, or analysis results are listed in the registry record; the number of recorded analyses is 0. The registry record also does not report a detailed statistical plan, including methods for estimating uncertainty, handling repeated events, or adjusting for covariates. These methods should not be presumed.

How should over-dispersion be understood?

In general, over-dispersion arises when variability in count data is greater than a chosen statistical model expects. It can make uncertainty estimates too narrow if a model assumes less variability than the data contain. This concern is most relevant to analyses of counts or event rates, particularly when individuals can experience repeated events. The posted primary outcome is defined as a percentage of participants, and the registry record does not report a count-rate model or an over-dispersion adjustment. It is therefore not possible to assess whether such a method was used or needed in a separate analysis.

What do the planning illustrations mean?

In general, a sample-size calculation is a planning exercise based on assumed effect size, significance level, allocation, and statistical method. It is not a summary of observed trial performance and should not be described as observed power. The planning assumptions associated with this record describe a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and effects defined as fractions of an observed effect. They explicitly describe a planning illustration rather than the trial's own design. Since this study is single-group and the registry record does not report a trial sample-size justification, those assumptions do not demonstrate that the study was designed as a two-arm randomized comparison. The registry record does not report a protocol-based sample-size justification.

For binary outcomes, general planning calculations commonly use a target probability of an event in each proposed group and a difference to detect. Such calculations depend on assumptions and are not evidence that an observed comparison occurred. The registry record does not report a comparative outcome analysis to which a two-arm planning illustration could be applied as an observed treatment effect. No planning output should be interpreted as the number actually enrolled or as a measure of efficacy or safety certainty.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists 60 outcome measures and 0 analyses. It does not report how multiplicity was handled. Multiplicity refers, in general, to the increased chance of at least one false-positive finding when multiple statistical hypotheses are tested. A stated adjustment method, testing hierarchy, or distinction between primary and exploratory analyses is not reported in the registry record. The number of outcomes alone does not establish how many were tested or whether any correction was applied.

Missing-data methods are not reported in the registry record. It does not state how participants who stopped treatment, missed visits, or had incomplete follow-up contributed to the primary endpoint summary. Because the endpoint is assessed over a long exposure and follow-up window, the handling of incomplete observation could affect the interpretation of an observed participant percentage. No assumptions about censoring, imputation, or exclusion should be inferred.

The record defines the safety population as participants from Studies C13004, C13006, C13007, and C13011 who received any amount of vedolizumab in Study C13008, plus de novo participants who received any amount of vedolizumab in Study C13008. It gives 2243 as the at-risk count for each adverse-event grouping. It does not report a participant flow accounting that would explain how this denominator relates to the overall enrollment of 2243 or detail any endpoint-specific exclusions.

In general, an analysis population should be described in relation to the estimand being reported: who is included, what outcome is counted, and how incomplete observations are treated. Here, the safety-population definition and event counts are available, but the registry record does not report further analysis-population details or procedures for missing data. These gaps limit assessment of whether all participants had comparable opportunity for event detection.

11. 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: crohn's disease (10.0%), colitis ulcerative (5.3%), abdominal pain (2.2%), anal abscess (1.5%), small intestinal obstruction (1.3%).

The adverse-event summary lists 2243 participants at risk for serious adverse events, with 825 affected, and 2243 at risk in the other adverse-event grouping, with 1820 affected. It also lists 10 deaths. These are reported counts; they do not alone indicate that treatment caused the events. The registry record defines serious adverse events by outcomes such as death, life-threatening events, inpatient hospitalization, persistent or significant disability, congenital anomaly or birth defect, and medically significant events.

The serious-event terms and their listed percentages are Crohn's disease, 10.0%; colitis ulcerative, 5.3%; abdominal pain, 2.2%; anal abscess, 1.5%; small intestinal obstruction, 1.3%; and pneumonia, 0.9%. The registry record does not report the denominator or calculation details for these term percentages, nor does it establish that each listed term represents a distinct participant. Participants may also have more than one event, so event terms should not be treated as mutually exclusive categories without supporting information.

In general, a serious-event listing identifies reported event types and does not establish a causal relationship. The record does not report whether the 10 deaths were considered related to vedolizumab. It also does not give a comparator against which to interpret the counts.

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

The results describe adverse events observed in a long-term, open-label, single-group study of vedolizumab among participants with ulcerative colitis and Crohn's disease. The registry lists serious-event and other-event counts, a death count, and percentages for several serious-event terms. The primary endpoint is defined as the percentage of participants with one or more TEAEs and SAEs, assessed from first dose through 16 weeks after the last dose, up to approximately 8.5 years.

These data can be read as a record of events during study participation and follow-up. They offer descriptive safety information for the stated population and event definitions. The study's long treatment schedule and follow-up window are relevant context for understanding the period in which events could be recorded.

The results do not show what would have happened to comparable participants without vedolizumab or under a different treatment. There is no control group, and the study was not masked. The event definitions do not require that an event be judged related to treatment, so the presence of an event is not proof of causation. Likewise, a listed event percentage is not, by itself, an estimate of excess risk attributable to the drug.

The registry record does not report a primary endpoint estimate with a confidence interval, p-value, or detailed statistical analysis. It also does not report methods for missing data or multiplicity. Without those details, readers cannot assess inferential precision or all aspects of the analysis population. The counts should not be turned into a claim that treatment works or does not work, nor do they answer a comparative efficacy question.

In general, interpretation of safety data depends on event definitions, follow-up, the population at risk, completeness of ascertainment, and whether a relevant comparator is available. Here, the record supplies the event definitions, exposure schedule, safety-population definition, and posted counts, but important analytic details are not reported in the registry record. The appropriate conclusion is therefore limited to describing the events recorded in this study, without attributing them to vedolizumab or generalizing a comparative effect.

13. Why This Trial Matters Statistically

This study is statistically notable for its focus on chronic exposure and safety follow-up in a mixed population with ulcerative colitis and Crohn's disease. The regimen is described as repeated intravenous vedolizumab administration, and the endpoint window extends from first dose through 16 weeks after the last dose, up to approximately 8.5 years. Long observation can capture events that a shorter follow-up period might not describe, although interpretation still depends on how consistently participants were followed.

The record also illustrates an important distinction between the total enrollment and a defined safety population. The safety population includes participants from several named studies who received vedolizumab in Study C13008, as well as de novo participants in that study. Careful reading of the population definition is essential before interpreting any denominator or comparing results across records.

Statistically, the single-group design makes the evidence descriptive rather than comparative. Event counts can characterize what was recorded among exposed participants, but they cannot separate treatment-associated events from events related to underlying disease or other causes. The large amount of follow-up context does not remove that design limitation.

The record's primary endpoint is clearly framed around participant-level occurrence of TEAEs and SAEs, but it does not report a primary estimate with uncertainty or a detailed analysis plan. This highlights why transparent reporting of denominators, missing-data handling, and statistical methods matters alongside event counts. It also shows why planning illustrations must be kept distinct from the actual single-group trial design: assumptions about two-arm allocation are not evidence that a randomized comparison took place.

Taken together, the study is informative as a long-term descriptive safety record, while its design and reporting set clear limits on causal interpretation and statistical precision.

14. 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 absence of a comparison group is a central limitation for interpreting the adverse-event counts. The study cannot directly quantify how event occurrence differed from an untreated group or an alternative treatment group. Open-label status is another design feature: treatment was not masked, and the registry record does not describe procedures that might address possible differences in event reporting or assessment.

The study population includes participants with two conditions, and the defined safety population draws on participants from multiple studies. The registry record does not report diagnosis-specific primary endpoint estimates or enough participant-flow detail to assess how these population features affect the pooled counts. The recorded enrollment is 2243, and the adverse-event summaries list 2243 at risk, but the record does not provide further reconciliation of the overall enrollment with the cross-study safety-population definition.

The primary endpoint is named and defined, yet a separate primary estimate, confidence interval, and p-value are not reported in the registry record. The record also does not report methods for missing data, repeated events, multiplicity, or adjustment for other factors. Those omissions limit assessment of precision, completeness of follow-up, and the robustness of any statistical interpretation.

The listed serious-event term percentages do not have a reported denominator or calculation detail in the registry record. The 10 recorded deaths are not accompanied by a reported causal assessment in the information available. Event terms should therefore be read as reported safety descriptions, not as evidence that vedolizumab caused each event.

Finally, the planning assumptions describe a two-arm illustration, whereas the study itself is recorded as single-group. That illustration is not the trial's design or a substitute for a study-specific sample-size justification, which is not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: An Open-label Study of Vedolizumab (MLN0002) in Participants With Ulcerative Colitis and Crohn's Disease — NCT00790933.
• Registry record last updated 2022-05-24; status last verified 2022-05.
• Results first posted 2019-03-12.
• 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.

18. Record Summary

The record describes NCT00790933, a completed Phase 3, multicenter, open-label, single-group study sponsored by Takeda. It enrolled 2243 participants with ulcerative colitis and Crohn's disease and evaluated vedolizumab 300 mg by 30-minute intravenous infusion every 4 weeks, beginning at Week 0, for approximately up to 510 weeks.

The primary endpoint was the percentage of participants with one or more treatment-emergent adverse events and serious adverse events, from first dose through 16 weeks after the last dose, up to approximately 8.5 years. The registry lists 825 affected participants among 2243 at risk for serious adverse events, 1820 affected among 2243 for the other adverse-event grouping, and 10 deaths. It does not report a comparative treatment effect, primary endpoint confidence interval, or detailed statistical analysis plan.