A Placebo-controlled Trial With rFXIII Administered to Subjects With Mild to Moderate Active Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Placebo-controlled Trial With rFXIII Administered to Subjects With Mild to Moderate Active Ulcerative Colitis (NCT01706159), a randomized phase 2 study. The primary outcome is Endoscopic Remission Defined as a Modified Baron Score of 0.

2. Clinical Question

3. Trial Design

This was a phase 2, randomized, double-blind, parallel-group, placebo-controlled trial of rFXIII in subjects with mild to moderate active ulcerative colitis. The official title describes a multicenter, multiple-dose study, and the brief summary says it was conducted in Europe. The sponsor is Novo Nordisk A/S. The registry lists enrollment as 20 and trial status as terminated. The start and primary-completion entries are 2012-10 and 2013-07.

The listed interventions were catridecacog and placebo. The arm descriptions contain no further details, so the dose, dosing schedule, and other treatment procedures are not reported in the registry record. Although the study is described as randomized and double-blind, the method used to generate or conceal the allocation and the practical details of masking are not reported in the registry record.

The primary endpoint was a binary response at week 8: endoscopic remission, defined as a modified Baron score of 0, versus non-remission, defined as a score of 1 or more. The stated primary analysis population was the full analysis set, comprising all randomized and treated subjects. The outcome entries list 13 participants in the rFXIII arm and 5 in the placebo arm, with 1 responder in each arm.

The registry lists 4 secondary outcomes: clinical and endoscopic remission, adverse events, rFXIII clearance, and maximum rFXIII concentration. It records 5 outcome measures and 1 analysis. The reason the trial was terminated, the intended recruitment target, and the operational details of trial conduct are not reported in the registry record.

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: No pre-assignments were given for this trial.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set (FAS) included all randomised and treated subjects.

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 demographics and baseline characteristics are presented for the Full analysis set (FAS) which included all randomised and treated subjects.

6. Primary Endpoint

The registry lists the primary outcome as Endoscopic Remission Defined as a Modified Baron Score of 0, measured over At week 8.

The primary endpoint was endoscopic remission at week 8. It was recorded as a binary outcome: a participant was a responder if the modified Baron score was 0, and a non-responder if the score was 1 or more. The measure focuses on the endoscopic assessment of the colonic mucosa rather than relying only on reported symptoms. That distinction can be useful in a clinical trial because symptoms and visible mucosal findings are different kinds of outcomes and may not move together.

In general, turning an endpoint into responder versus non-responder makes the outcome straightforward to summarize as counts and to analyze with methods for binary data. It also means that the threshold matters: results depend on the stated definition of remission. A binary endpoint does not show how far a participant’s score was from the threshold, or describe changes among those who remain classified as non-responders.

The registry defines the full analysis set as all randomized and treated subjects. The posted arm entries report 1 responder among 13 participants assigned to rFXIII and 1 among 5 assigned to placebo. The registry does not explain whether endoscopic assessments were centrally read, how assessments were handled if unavailable, or whether any additional endpoint rules were used. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical context. A binary endpoint records whether each participant meets a defined event criterion. For this trial, the event was endoscopic remission at week 8, defined as a modified Baron score of 0. Participants with a score of 1 or more were classified as non-responders. This approach gives a clear event count, but it discards distinctions among scores within either category and makes the choice of threshold consequential.

What does the logistic-regression odds ratio represent?

General statistical context. Logistic regression is commonly used when the outcome has two categories. It models the odds of the event and can report an odds ratio for a contrast between groups. An odds ratio of 1 represents equal odds under the modeled contrast; values on either side indicate different estimated odds. An odds ratio is not a difference in response rates, and it should not be interpreted as a risk ratio. The registry reports an odds ratio of 0.16 for the comparison listing rFXIII and placebo, but the model’s coding and any covariate specification are not reported in the registry record. The reported value should therefore be read alongside the endpoint counts and with that limitation in mind.

How should the confidence interval be read?

General statistical context. A confidence interval describes the range of estimates compatible with the data and the specified statistical procedure, under its assumptions. It is not a range that guarantees the true effect lies within it. The registry gives a 90% confidence interval from 0.01 to 3.05. Because this interval spans the null value of 1 and is wide, the reported estimate is imprecise: the data do not sharply distinguish among a range of possible odds-ratio values. The interval is at 90%, as reported; it should not be silently treated as a different confidence level.

What does the p-value add?

General statistical context. A p-value measures how unusual data at least as incompatible with a specified null hypothesis would be if that hypothesis and the model assumptions were true. It is not the probability that the null hypothesis is true, nor does it measure the size or clinical importance of an effect. The reported p-value is 0.306. Read together with the wide confidence interval and sparse counts, it does not provide strong evidence against the null under the reported analysis. It also does not demonstrate that the groups are equivalent.

Why do small counts matter?

General statistical context. When event counts are sparse, estimates can be unstable: changing the classification of an individual participant can substantially alter the estimated comparison. Standard model-based intervals and tests also depend on assumptions about the data and model. The posted outcome entries show 1 responder in each group, with different group sizes. Those counts leave little event information for estimating a comparative effect. The record does not describe any small-sample correction or alternative analysis; such methods are not reported in the registry record.

What is known about the analysis population and missing outcomes?

The registry defines the full analysis set as all randomized and treated subjects. In general, the population definition identifies which participants are intended to contribute to the primary analysis, but it does not by itself explain how missing endpoint observations are treated. The registry does not report the number of missing week 8 assessments, an imputation method, or a sensitivity analysis for missing outcomes. Those details are not reported in the registry record.

How should planning illustrations be distinguished from trial results?

The planning assumptions describe an illustration based on the observed effect, not the trial’s own design: a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect expressed as a stated fraction of the observed effect. For non-time-to-event outcomes, the illustrations are expressed as participants per arm. Such calculations are planning illustrations, not observed power and not evidence that the trial was designed around those assumptions. The registry does not report the trial’s original sample-size justification or statistical plan.

10. Exact Estimates for Each Arm

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

R code and output

arm    <- c("rFXIII", "Placebo")
n      <- c(13, 5)
events <- c(1, 1)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  rFXIII  13  1  7.7  0.2  36.0  1.4  33.3  1.8  33.9
ARM  Placebo  5  1  20.0  0.5  71.6  3.6  62.4  4.3  64.1

11. Analyses Reported by the Sponsor

The registry’s reported comparison is a logistic-regression analysis, with an odds ratio of 0.16, a 90% confidence interval from 0.01 to 3.05, and p = 0.306. The same record lists 1 responder in the rFXIII arm and 1 in the placebo arm. The regression estimate is the sponsor’s posted analysis; the registry does not provide a separate numerical recalculation to compare with it.

The record does not state the regression model’s coding details, covariates, or other specifications. The odds ratio should therefore be reported as stated rather than reverse-engineered from the arm counts. The counts and the model-based estimate answer related but not identical descriptive questions: the counts give the observed events and group sizes, while the regression result is the reported modeled comparison. The registry does not explain the relationship between the two beyond listing them as the endpoint data and analysis.

The confidence interval is broad and spans 1, so the sponsor’s estimate is imprecise. The p-value is 0.306. Neither statistic supports a claim of demonstrated equivalence, and neither should be treated as a measure of clinical importance. There is no discrepancy flagged between a recalculation and the reported analysis in the available record. The sponsor’s stated regression result remains the appropriate result to quote when describing the registry’s formal analysis.

12. Multiplicity, Missing Data and Analysis Populations

The registry lists 5 outcome measures, including the primary endpoint and 4 secondary outcomes: clinical and endoscopic remission, adverse events, rFXIII clearance, and maximum rFXIII concentration. It records 1 analysis. The primary outcome is identified as endoscopic remission at week 8. The registry does not describe a multiplicity strategy, such as an adjustment to account for testing several outcomes, or a hierarchy governing interpretation of secondary outcomes. Those details are not reported in the registry record.

In general, evaluating multiple outcomes can increase the chance that at least one result appears notable by chance, particularly if each is tested separately. An adjustment or prespecified hierarchy can address that issue, but neither should be assumed without documentation. The listed secondary outcomes span remission, safety, and pharmacokinetic measures; they are not interchangeable measures of the same question. Their presence does not establish that each had a confirmatory role.

The stated primary population is the full analysis set, defined as all randomized and treated subjects. The registry does not describe a per-protocol population or provide further analysis-population definitions. It also does not report the number of missing primary-endpoint assessments, reasons for missingness, imputation procedures, or sensitivity analyses. In general, missing endpoint data can affect a binary response analysis if the likelihood of being assessed is related to group assignment or outcome status. Without the missing-data details, the extent and direction of any such effect cannot be evaluated.

The registry reports the trial as terminated, but the reason and any resulting consequences for the analysis are not reported in the registry record. It does not state whether termination affected the planned outcome schedule, recruitment target, or analysis plan. These omissions limit assessment of selective outcome reporting and the handling of incomplete data. They do not establish that such problems occurred; they mean that the record does not allow them to be assessed.

13. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 (7.7%).

The registry lists serious adverse events for the rFXIII arm as 1 affected participant among 13 at risk, and for placebo as 0 among 5 at risk. It also lists other adverse events affecting 2 participants in each arm, with 13 at risk for rFXIII and 5 at risk for placebo. The most frequent serious-event term is listed as “Colitis ulcerative,” with 7.7%. The registry does not provide further detail about the event’s timing, severity beyond its serious classification, or relationship to study treatment.

These figures are counts from a small trial and should be read descriptively. They do not establish whether the observed events were caused by an intervention, nor do they provide a precise comparison of safety between groups. The posted serious-event counts are not the same as an assessment of all possible harms, and the count of other adverse events is reported separately.

Deaths are not reported in the registry record. The meaning of the 7.7% entry is not further explained in the available record, so its denominator and calculation should not be inferred. The figures do not support medical advice or a broad safety conclusion.

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

The central statistical finding is that the registry records 1 endoscopic-remission responder in each arm at week 8. The reported logistic-regression odds ratio is 0.16, with a 90% confidence interval from 0.01 to 3.05 and p = 0.306. The interval is wide and spans the odds-ratio null value of 1. The available endpoint information therefore does not estimate the comparative effect precisely.

This result does not show that the treatments are equivalent. A non-significant p-value is not proof of no difference, and the wide interval leaves uncertainty about the size and direction of the modeled contrast. Nor does the reported odds ratio establish a clinically important benefit or harm. The trial’s small outcome counts are a key reason to avoid treating the point estimate as definitive.

The endpoint is specifically endoscopic remission using a modified Baron score threshold. It does not, by itself, answer every question about clinical remission, symptom burden, adverse events, or rFXIII pharmacokinetics. Those areas appear among the secondary outcomes, but detailed results for them are not included in the registry entries apart from the adverse-event entries. The registry record does not describe how missing endoscopic assessments were handled or provide the full statistical plan.

The trial is listed as terminated, but the reason is not reported in the registry record. That status cannot, on its own, explain the outcome or establish why the trial ended. The appropriate interpretation is limited to the posted data: a small number of observed endpoint events, an imprecise regression estimate, and important analysis details that are not reported in the registry record. These results are not a basis for treatment decisions.

15. Why This Trial Matters Statistically

This trial illustrates how a clearly defined binary endpoint can still yield an uncertain comparison when event counts are sparse. Endoscopic remission was defined using a specific threshold, making the responder outcome easy to state, but the posted results contain only 1 responder in each arm. With so few events, the estimated odds ratio can be highly sensitive to individual observations, and the resulting confidence interval is broad.

The record also demonstrates why an odds ratio should be read with its uncertainty interval and the underlying counts. The reported odds ratio of 0.16 may appear to be a precise statement when viewed alone, but the 90% confidence interval from 0.01 to 3.05 spans the null value and a broad range of possible comparisons. The p-value of 0.306 does not settle the question of whether an effect exists, and it does not establish equivalence.

Several features make careful reporting especially important: the trial is listed as terminated; the reason for termination is not reported in the registry record; and details of missing data and the statistical plan are also not reported. The stated full analysis set definition is useful, but it does not answer how unavailable endpoint measurements were handled. Distinguishing documented information from unreported details prevents speculation from being mistaken for evidence.

The case is a useful reminder that trial design labels, a model-based estimate, and observed event counts each convey different information. Randomization and double blinding describe design features, while they do not remove uncertainty from a sparse endpoint. A transparent reading keeps the focus on the scale and precision of the result, rather than treating a single point estimate as a complete account.

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 few observed responders: 1 in each arm. The arm entries list 13 participants for rFXIII and 5 for placebo. This sparse outcome makes the comparative estimate imprecise, as reflected in the 90% confidence interval from 0.01 to 3.05. The registry does not give confidence intervals for the arm-specific response rates.

The registry lists enrollment as 20, while the primary-outcome entries list 13 and 5 participants. It does not explain the relationship between the enrollment figure and the endpoint denominators. This should be recorded as an unresolved reporting detail, not interpreted as evidence of a particular exclusion, missing-data pattern, or analysis decision.

The trial is marked terminated, but the reason for termination is not reported in the registry record. The record also does not explain whether termination altered the planned recruitment, assessment schedule, or analysis. Dose and schedule details are absent from the arm descriptions, and the implementation of randomization and masking is not described.

Further limitations concern analysis transparency. The regression model’s coding and covariates are not reported. Missing endpoint counts and their handling are not reported, and neither is the statistical plan or the approach to multiple outcomes. The full analysis set is defined as all randomized and treated subjects, but the definition alone does not resolve those issues. These gaps constrain interpretation of the posted comparison and should not be filled by assumptions.

17. Related Tutorials

18. Related Statistical Calculators

19. Sources

• ClinicalTrials.gov: A Placebo-controlled Trial With rFXIII Administered to Subjects With Mild to Moderate Active Ulcerative Colitis — NCT01706159.
• Registry record last updated 2014-10-02; status last verified 2014-09.
• Results first posted 2014-08-05.
• 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

This phase 2 study was a randomized, double-blind, parallel-group, placebo-controlled, multiple-dose trial of rFXIII in subjects with mild to moderate active ulcerative colitis. The registry lists enrollment as 20 and status as terminated. Its primary endpoint was endoscopic remission at week 8, defined as a modified Baron score of 0; scores of 1 or more were classified as non-remission. The primary population was the full analysis set of all randomized and treated subjects.

The primary-outcome entries list 1 responder among 13 participants in the rFXIII arm and 1 among 5 in the placebo arm. The reported logistic-regression odds ratio is 0.16, with a 90% confidence interval from 0.01 to 3.05 and p = 0.306. The interval indicates substantial uncertainty. The reason for termination, missing-data procedures, and full statistical plan are not reported in the registry record.