Efficacy and Safety of Oral BT-11 in Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Oral BT-11 in Ulcerative Colitis (NCT03861143), a randomized phase 2 study. The primary outcome is Clinical Remission.

2. Clinical Question

The trial asks whether clinical remission at Week 12 differed between participants assigned to either of two once-daily oral BT-11 doses and participants assigned to placebo. The registry describes a phase 2 randomized, placebo-controlled study in ulcerative colitis, with clinical remission as its posted primary outcome.

The results address the specified Week 12 outcome in the listed ITT population. They do not, by themselves, establish what happened at other time points or during the optional extension. No secondary outcome results are posted in the registry record, so the available efficacy interpretation is centered on this primary endpoint.

3. Trial Design

The registry describes NCT03861143 as a phase 2 randomized, parallel-group study of oral BT-11 in ulcerative colitis, with placebo as the comparator. The official title identifies the study as multicenter and double-blind; the masking field classifies masking as triple. The registry does not explain which roles were masked or how masking was maintained.

The three listed groups received BT-11 440 mg, BT-11 880 mg, or placebo, each as an oral once-daily tablet. The primary outcome results list 66 participants per arm. The total enrollment is 198. The registry does not report details of the randomization sequence, allocation concealment, site count, or whether any participants were excluded from the primary analysis.

The brief summary describes induction, maintenance, and an optional open-label extension period. The primary outcome is assessed at Week 12; the registry does not provide further timing details for the other periods or say how many participants entered the extension. The trial is recorded as completed. Its recorded start date is 2019-08-14 and its primary completion date is 2020-12-10.

The sponsor is NImmune Biopharma. The study's stated purpose was to evaluate efficacy and safety of oral BT-11 compared with placebo in ulcerative colitis. The registry outcome results give remission percentages and group counts, but the registry record does not report the original design assumptions, the planned analysis model, or a statistical analysis plan. Those omissions limit what can be inferred about how the trial was intended to distinguish dose effects or handle design and analysis choices.

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

Analysis population for the primary outcome, as defined in the registry: ITT

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 Clinical Remission, measured over Week 12.

The primary endpoint is clinical remission at Week 12, expressed as the percentage of participants meeting the registry definition. That definition requires a rectal bleeding subscore of 0, a stool frequency subscore of 0 or 1, and an endoscopic subscore of 0 or 1 on the 3-component modified Mayo Score. The listed analysis population is ITT.

A binary endpoint classifies each participant as meeting or not meeting the stated criteria at the specified assessment. Reporting the percentage meeting those criteria makes the group outcome interpretable as a remission rate, while the participant counts show how many people contributed to the reported result. These measures describe the observed classification under the registry definition; they do not provide detail about symptom changes that fall short of the threshold or changes in individual score components.

General: a composite clinical endpoint combines multiple criteria into one outcome. This can make a result depend on every component in the definition: a participant must satisfy all listed conditions to count as being in remission. The registry does not report separate component results, so the posted outcome cannot show which component most often determined whether participants met the remission definition.

Week 12 anchors the interpretation to a particular assessment time. The result does not directly describe remission at other visits, during maintenance, or in the optional open-label extension. The registry record does not report details of endpoint assessment procedures, handling of missing Week 12 observations, or additional endpoint definitions.

7. Results Posted in the Registry

• BT-11 Low-dose (440 mg): 30.3% (20/66) versus 22.7% (15/66) on control; risk difference 7.6 percentage points (95% CI -7.4 to 22.6), risk ratio 1.33 (0.75–2.37); unadjusted two-proportion z-test p = 0.324.
• BT-11 High-dose (880 mg): 31.8% (21/66) versus 22.7% (15/66) on control; risk difference 9.1 percentage points (95% CI -6.0 to 24.2), risk ratio 1.40 (0.79–2.47); unadjusted two-proportion z-test p = 0.241.

8. Statistical Interpretation

9. Statistical Methods Explained

The primary outcome is binary: participants either met the Week 12 clinical remission definition or did not. The registry reports the percentage meeting the definition and the number of participants in each group. Counts and percentages are complementary: the percentage communicates the proportion in remission, while the count makes the underlying number of observed events visible. The listed population is ITT, but details of how that population was defined and analyzed are not reported in the registry record.

What does a risk difference represent?

General: a risk difference is the event proportion in one group minus the event proportion in a comparison group. It is an absolute contrast, measured on the same scale as the event proportion. The posted recalculated unadjusted estimates compare each BT-11 arm with placebo: 0.076 for 440 mg and 0.091 for 880 mg. The corresponding intervals are -0.074 to 0.226 and -0.060 to 0.242. Because each interval spans zero, the observed contrast is not precisely separated from no difference by these estimates.

The comparison is unadjusted: it uses the posted group summaries and does not account for additional covariates. The registry record does not report a covariate-adjusted analysis, stratification factors, or a model specification. An unadjusted comparison can be useful for describing the recorded group proportions, but it should not be represented as an adjusted sponsor analysis.

How do relative measures differ?

General: a risk ratio compares event proportions as a ratio, while an odds ratio compares the odds of the event. These relative scales answer a different descriptive question from the absolute risk difference. The risk ratio and odds ratio estimates and intervals are also posted for both dose-versus-placebo comparisons. For 440 mg, the risk ratio is 1.333 (0.750 to 2.372) and the odds ratio is 1.478 (0.678 to 3.222). For 880 mg, the risk ratio is 1.4 (0.793 to 2.471) and the odds ratio is 1.587 (0.731 to 3.442). The intervals for these ratios include 1, which represents no relative contrast.

Different effect scales can make a comparison easier to interpret for different purposes, but none changes the underlying trial observations. The risk difference describes an absolute contrast; the ratios describe relative contrasts. The registry does not identify one of these scales as the prespecified primary statistical measure. The endpoint itself remains the percentage meeting the remission criteria.

What does a confidence interval communicate?

General: a confidence interval gives a range of estimates compatible with the observed data and the interval method. Its width indicates precision: a wider interval leaves more uncertainty about the magnitude and possibly the direction of the contrast. An interval that includes the null value does not prove that the groups are equivalent; it means the estimate is compatible with a range that includes no contrast under the method used. The registry does not state the confidence level or the interval construction method, so those details should not be assumed.

The unadjusted p-values are 0.324 for the 440 mg comparison and 0.241 for the 880 mg comparison. General: a p-value describes how unusual data at least as inconsistent with a specified null model would be if that model and the test assumptions held. It is not the probability that a treatment effect is true, nor a measure of clinical importance. The registry labels these values unadjusted; it does not report the test procedure or an adjustment for making comparisons involving both dose groups.

There are no posted analysis records in the registry, although the outcome results allow simple recalculated comparisons from the observed counts. These recalculations do not supply missing details about the trial's planned analysis. The registry record does not report its own statistical analysis plan, missing-data approach, interim analysis plan, or original sample-size justification. The posted arm summaries and recalculated contrasts should therefore be interpreted as descriptive statistical evidence rather than as a complete account of the trial's prespecified inferential strategy.

General: over-dispersion is a concern in some statistical models when observed variability exceeds what a model assumes. It can affect standard errors and intervals if the model does not account for that extra variability. The posted endpoint is a binary remission outcome with group counts; no over-dispersion model is reported or needed to interpret the direct group proportions. The registry record does not report model diagnostics or a model-based analysis that would allow further assessment on this point.

10. Confidence Intervals and Precision

The Week 12 remission estimates are accompanied by intervals for each BT-11-versus-placebo contrast. For 440 mg, the recalculated risk difference is 0.076, with an interval from -0.074 to 0.226. For 880 mg, it is 0.091, with an interval from -0.060 to 0.242. Both intervals include zero, so the posted summaries leave uncertainty about whether the underlying absolute contrast is negative, absent, or positive.

The intervals are broad relative to their point estimates, indicating that the estimated contrasts are not highly precise. Their span also permits contrasts meaningfully different from the point estimate. This cautions against treating the observed percentage differences as settled estimates of the underlying effect. The intervals do not prove that the groups are equivalent or that a particular effect is absent.

The ratio-scale intervals communicate a similar uncertainty in a different form. For the 440 mg comparison, the risk ratio interval is 0.750 to 2.372 and the odds ratio interval is 0.678 to 3.222. For 880 mg, the risk ratio interval is 0.793 to 2.471 and the odds ratio interval is 0.731 to 3.442. Each ratio interval includes 1, the value corresponding to no relative contrast.

General: an interval's precision depends on the data and the method used to calculate it. A point estimate alone hides this uncertainty, and an interval should be read as a range rather than as a guarantee that the true value lies inside it. The registry does not report the confidence level or interval method, so neither should be inferred from the posted limits.

The group sizes are 66 per arm, and the remission counts are 20, 21, and 15 for the 440 mg, 880 mg, and placebo arms, respectively. Those observed counts give context to the estimates, but do not remove uncertainty. The p-values are unadjusted, and the registry does not report a multiplicity adjustment. The precision statements apply to the posted unadjusted comparisons, not to an unreported adjusted analysis.

11. 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 displayed planning values are participants per arm, not total events. They are planning illustrations based on the observed effect, rather than a description of the trial's original design. The listed assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. Each planning scenario uses the stated fraction of the observed effect as the effect to detect.

For the 440 mg comparison, planning for 100% of the observed effect gives 532 participants per arm for 80% power and 712 participants per arm for 90% power. Planning for 75% of the observed effect gives 925 participants per arm for 80% power and 1,237 participants per arm for 90% power. Planning for 50% of the observed effect gives 2,030 participants per arm for 80% power and 2,717 participants per arm for 90% power.

For the 880 mg comparison, planning for 100% of the observed effect gives 376 participants per arm for 80% power and 503 participants per arm for 90% power. Planning for 75% of the observed effect gives 651 participants per arm for 80% power and 871 participants per arm for 90% power. Planning for 50% of the observed effect gives 1,424 participants per arm for 80% power and 1,906 participants per arm for 90% power.

General: power is the chance that a planned statistical test will detect an effect of the specified size under its assumptions. The 80% and 90% columns describe different planning targets, not results observed in the completed trial. For a fixed power target, planning to detect a smaller effect requires more participants, as the displayed scenarios illustrate. A curve should be read as the same relationship across the planning choices: smaller target effects correspond to larger participant requirements under these assumptions.

These figures are not observed power. The trial's own original sample-size justification and design assumptions are not reported in the registry record, and these illustrations should not be substituted for them.

12. 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 = 0.227; treatment proportion p₁ = 0.303; average p̄ = 0.265.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6243 = 1.2235.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.6220 = 0.5234.
4. n = (1.2235 + 0.5234)² / (0.0758)² = 531.8, rounded up to 532 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 <- 0.227272727272727                          # control proportion
p1 <- 0.303030303030303                          # 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(3861143)
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 = 532 (80% power), 712 (90% power)
 75% of observed effect: n per arm = 925 (80% power), 1,237 (90% power)
 50% of observed effect: n per arm = 2,030 (80% power), 2,717 (90% power)
power.prop.test: 531.8 
Simulated power at n = 532 per arm: 0.803 (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.

13. Multiplicity, Missing Data and Analysis Populations

The registry posts one primary outcome measure: Week 12 clinical remission. It reports comparisons of each BT-11 dose with placebo. The registry does not report secondary outcome results, and it lists zero posted analysis records. It also does not report a prespecified multiplicity strategy, such as a method for controlling error across the dose comparisons or across outcome tests.

General: multiplicity arises when several statistical hypotheses are assessed. Without an appropriate plan, interpreting multiple unadjusted p-values as though they were the only test can make evidence appear more conclusive than it is. The two posted comparisons have unadjusted p-values of 0.324 and 0.241. Because no adjustment method is reported, these should be read as unadjusted comparisons rather than as multiplicity-controlled results. The registry record does not establish whether any adjustment was used in a separate sponsor analysis.

The primary population is labeled ITT, but the registry does not report the operational definition of that population, whether all randomized participants were included in the outcome denominator, or how deviations from assigned treatment were handled. The outcome results list 66 participants for each arm. The missing-data method for participants without an observed Week 12 assessment is not reported in the registry record. No imputation method, missingness assumption, or sensitivity analysis is described.

The registry record also does not report whether interim analyses were planned or conducted, whether there were stopping rules, or how protocol deviations and withdrawals were handled. These are unknown from the posted registry information; no particular approach should be inferred.

These omissions matter because analysis choices can affect estimates, uncertainty, and interpretation. The available results support description of the reported arm percentages and unadjusted contrasts, but do not provide a complete account of the trial's inferential safeguards or missing-data handling. No conclusion about those unreported methods can be drawn from the arm summaries alone.

14. 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 (1.5%), proctitis (1.5%), amoebiasis (1.5%), pneumonia (1.5%), pneumonia viral (1.5%).

The registry reports serious adverse events for 2 of 66 participants in the BT-11 440 mg group, 3 of 66 in the 880 mg group, and 3 of 66 in the placebo group. It reports zero deaths in each of the three arms. These are participant counts, not a complete description of the nature, timing, severity, or duration of all adverse events.

The listed serious-event terms include Colitis Ulcerative, Proctitis, Amoebiasis, Pneumonia, Pneumonia Viral, and Foot Fracture, each reported as 1.5%. The registry does not identify those terms by treatment arm in the listed summary, so they should not be assigned to a particular group from this information. A term's appearance in the list does not show whether it was considered related to study treatment.

Other adverse events are reported for 23 of 66 participants in the 440 mg group, 29 of 66 in the 880 mg group, and 27 of 66 in placebo. The registry's summary does not provide further event-level detail for those counts. Comparisons across these counts are descriptive; the record does not report a statistical safety analysis, exposure-adjusted rates, or an assessment of causality. These figures describe the posted safety counts and are not, on their own, a complete safety evaluation.

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

The posted data show that the Week 12 clinical remission percentage was 30.3% in the BT-11 440 mg arm, 31.8% in the 880 mg arm, and 22.7% in the placebo arm. The corresponding recalculated unadjusted risk differences versus placebo are 0.076 and 0.091. These are the observed results for the registry-defined primary endpoint in the listed ITT population.

The uncertainty intervals for both risk differences include zero, and the relative-measure intervals include 1. The unadjusted p-values are 0.324 and 0.241. Together, these statistics show that the observed group contrasts are uncertain and not estimated precisely enough to treat the point estimates as definitive. They do not establish equivalence, and they do not determine whether any difference would be clinically important.

General: a clinical trial estimate is not a promise of what will happen to an individual, and a group-level contrast does not describe every participant's experience. Statistical uncertainty concerns the range of effects compatible with the data and method; clinical importance requires interpretation beyond the point estimate alone. The registry does not provide a threshold for a clinically important difference.

The outcome is limited to the Week 12 remission definition. It does not show separate results for rectal bleeding, stool frequency, or endoscopic subscores, and no secondary outcome results are posted. Nor does it establish results during maintenance or the optional open-label extension. The record does not report extension participation or later outcomes.

The safety record lists serious adverse events in each arm and zero deaths in all arms, along with counts for other adverse events. These summaries should not be interpreted as complete causal comparisons: event detail, treatment attribution, and formal safety analyses are not reported. Overall, the registry supports a careful description of the observed outcome counts and their uncertainty, but not a broad claim about benefit, lack of benefit, or safety.

16. Why This Trial Matters Statistically

This trial illustrates why an observed difference in group percentages needs to be considered alongside its uncertainty. The Week 12 remission percentages are higher in each BT-11 arm than in placebo, but the recalculated risk-difference intervals extend across zero. The corresponding ratio intervals include 1. The point estimates therefore do not tell the full statistical story, and the intervals leave substantial uncertainty about the underlying contrasts.

The study has three groups with 66 participants in each listed outcome arm. The remission counts are 20, 21, and 15. These concrete denominators help readers understand how the percentages arise, while also reminding them that group summaries can be imprecise. A small-looking difference in percentages should not be interpreted as conclusive without considering the interval and analysis context.

Comparing two dose groups with the same placebo group also raises a multiplicity question. The registry presents unadjusted p-values but does not report a correction strategy or the original analysis plan. This makes it important to distinguish the straightforward recalculated contrasts from any claim about prespecified statistical testing. The registry does not report sponsor analysis records that could resolve this uncertainty.

The planning illustrations also highlight the connection between target effect size and participant requirements. Under the stated planning assumptions, targeting a smaller fraction of the observed effect requires more participants per arm. These illustrations are not evidence of the trial's original design rationale and are not observed power; the original sample-size assumptions are not reported.

More broadly, the record demonstrates the limits of registry summaries. It reports a defined primary endpoint, arm counts, comparisons, and safety totals, but does not report missing-data methods, analysis details, or secondary outcome results. Statistical interpretation is strongest when it stays close to what the record actually describes and acknowledges the uncertainty around both the estimates and the unreported methods.

17. 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.

The registry results focus on clinical remission at Week 12. They do not provide component-level results for rectal bleeding, stool frequency, or endoscopy, nor do they report secondary outcome results. The trial summary includes induction, maintenance, and an optional open-label extension, but outcome details beyond the primary Week 12 assessment are not reported in the registry record.

The results list 66 participants per arm and give remission counts for each group. The registry does not report how participants with missing Week 12 outcome data were handled, whether the listed denominators include all randomized participants, or what sensitivity analyses were performed. Although the primary population is labeled ITT, the operational definition and implementation are not described.

The comparisons are recalculated unadjusted contrasts from the posted summary statistics. The registry does not report the original analysis plan, an adjusted model, a multiplicity procedure, or the interval method and confidence level. It also does not report the trial's original sample-size justification or interim analysis details. These absences prevent a complete assessment of the prespecified inferential approach.

The registry classifies masking as triple while its brief summary calls the study double-blind; it does not explain the difference or identify who was masked. The record gives no further details on randomization implementation, allocation concealment, site count, eligibility criteria, or endpoint assessment procedures.

Safety information is presented as counts and selected serious-event terms. The record does not provide event-level timing, duration, treatment attribution, or a formal comparative safety analysis. These limitations do not invalidate the reported summaries, but they constrain how broadly the efficacy and safety findings can be interpreted.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Efficacy and Safety of Oral BT-11 in Ulcerative Colitis — NCT03861143.
• Registry record last updated 2023-06-29; status last verified 2023-06.
• Results first posted 2022-11-03.
• 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.

21. Record Summary

NCT03861143 is a completed phase 2 randomized, parallel-group study of oral BT-11 in ulcerative colitis, sponsored by NImmune Biopharma. The registry describes placebo control and multicenter conduct; its masking field says triple, while the brief summary calls the study double-blind. The recorded start date is 2019-08-14, and the primary completion date is 2020-12-10.

The posted primary outcome is clinical remission at Week 12, defined using rectal bleeding, stool frequency, and endoscopic subscores from the 3-component modified Mayo Score. The listed ITT results are 30.3% for BT-11 440 mg, 31.8% for BT-11 880 mg, and 22.7% for placebo, with 66 participants per arm.

The recalculated unadjusted risk-difference intervals include zero for both dose comparisons. The registry also posts serious adverse-event counts of 2, 3, and 3 participants across the 440 mg, 880 mg, and placebo groups, respectively, and zero deaths in each group. The original analysis plan, missing-data methods, multiplicity strategy, and sample-size justification are not reported in the registry record.