An Efficacy and Safety Study of Ontamalimab as Maintenance Therapy in Participants With Moderate to Severe Ulcerative Colitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Efficacy and Safety Study of Ontamalimab as Maintenance Therapy in Participants With Moderate to Severe Ulcerative Colitis (NCT03290781), a randomized phase 3 study. The primary outcome is Number of Participants With Remission Based on Composite Score at Week 52.

2. Clinical Question

The study record describes a maintenance question: among participants who responded during induction, did participants assigned to continue ontamalimab meet the composite remission definition at Week 52 more often than participants assigned to matched placebo? The posted results contain two dose-level comparisons. They report counts for the two maintenance ontamalimab groups and their corresponding placebo groups, while the sponsor’s analyses report differences in proportions for those comparisons.

The clinical question is bounded by the enrolled population and the endpoint definition. It does not ask whether ontamalimab induces an initial response, because the study is described as maintenance therapy after response in induction studies. Nor does the primary endpoint by itself describe every aspect of ulcerative colitis activity, quality of life, or longer-term outcomes. The registry record does not report results beyond the stated Week 52 timeframe for this endpoint.

3. Trial Design

This was a phase 3, randomized, double-blind, parallel-group, placebo-controlled study of ontamalimab as maintenance therapy for moderate to severe ulcerative colitis. The registry lists enrollment as 366 and the study status as completed. The recorded start date is 2018-04-04 and the primary completion date is 2021-07-01. Shire is listed as the sponsor.

The interventions listed are ontamalimab and placebo. The arm names distinguish treatment received in the induction study from maintenance assignment: for example, ONTA 25 mg/ONTA 25 mg denotes ontamalimab at 25 mg in both stages, while ONTA 25 mg/Placebo denotes prior 25 mg ontamalimab followed by placebo maintenance. Corresponding 75 mg arms are also listed. The primary results include 25 mg maintenance compared with ONTA 25 mg/Placebo and 75 mg maintenance compared with ONTA 75 mg/Placebo.

The arm descriptions state that participants had achieved a clinical response in one of the induction studies. They describe subcutaneous maintenance treatment and a schedule of every four weeks up to Week 52 for the 75 mg and placebo descriptions. The 25 mg description ends before its dosing schedule is complete, so that schedule is not reported in the registry record. The registry record does not report the randomization ratio or the allocation sequence details.

Double masking means that the study is recorded as double-blind, but the registry record does not specify which roles were masked or how masking was maintained. The parallel-group designation indicates separate groups followed under their assigned study arms; additional operational details are not reported in the registry record. The record identifies 13 outcome measures and 16 analyses. The original protocol’s sample-size justification and other original design assumptions 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: Participant with moderate to severe Ulcerative Colitis (UC) who achieved a clinical response and completed their treatment period in the induction studies (either SHP647-301 \[NCT03259334\] or SHP647-302 \[NCT03259308\]) were randomized into this study as ontamalimab and placebo responders to receive placebo or ONTA 25 milligrams (mg) or 75 mg.

Only the first 6 of 7 groups are shown.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The ontamalimab responder full analysis set (FAS) consisted of all participants in the randomized set who received at least 1 dose of IP in this study and who were previously treated with ontamalimab in the induction studies (SHP647-301 \[NCT03259334\] and SHP647-302 \[NCT03259308\]). As Pre-specified in protocol all efficacy analyses data were collected and analyzed based on ontamalimab responder (i.e ONTA 25mg/ Placebo, ONTA 25mg/ONTA 25mg, ONTA 75mg/Placebo and ONTA 75mg/ONTA 75mg arms only).

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 safety set consisted of all participants who had received at least 1 dose of Investigational Product (IP) in this study, regardless of treatment received during the induction studies (SHP647-301 \[NCT03259334\] and SHP647-302 \[NCT03259308\]).

Only the first 6 of 8 groups are shown.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Remission Based on Composite Score at Week 52, measured over At Week 52.

The primary endpoint is the number of participants with remission based on a composite score at Week 52. The definition combines participant-reported symptoms recorded in a daily e-diary with centrally read endoscopy. Remission requires a stool frequency sub-score of 0 or 1 with at least a 1-point change from induction-study baseline, a rectal bleeding sub-score of 0, and an endoscopic sub-score of 0 or 1. The endoscopic assessment is modified to exclude friability.

The composite uses the Mayo score without the Physician global assessment sub-score. The composite ranges from 0-9 points; the Mayo score ranges from 0-12 points and comprises four sub-scores graded from 0-3, with higher scores indicating more severe disease. The registry describes stool frequency, rectal bleeding, the Physician global assessment, and endoscopy as the component domains. For the primary remission definition, the relevant symptom and endoscopic thresholds are stated separately, so the endpoint is a threshold-based combination rather than simply a low total score.

Using both reported symptoms and centrally read endoscopy gives the endpoint more than one source of information about disease activity. In general, a composite can capture several clinically relevant dimensions, but its interpretation depends on its precise components and thresholds. A participant counted as meeting this endpoint must meet each stated condition. The registry record does not report further details about endpoint adjudication or how missing diary or endoscopy assessments were handled.

7. Results Posted in the Registry

• ONTA 25 mg/ONTA 25 mg: 53.5% (38/71) versus 8.2% (6/73) on control; risk difference 45.3 percentage points (95% CI 32.1 to 58.5), risk ratio 6.51 (2.94–14.44); unadjusted two-proportion z-test p = <0.001.
• ONTA 75 mg/Placebo: 12.8% (11/86) versus 8.2% (6/73) on control; risk difference 4.6 percentage points (95% CI -4.9 to 14.0), risk ratio 1.56 (0.61–4.00); unadjusted two-proportion z-test p = 0.353.
• ONTA 75 mg/ONTA 75 mg: 40.2% (33/82) versus 8.2% (6/73) on control; risk difference 32.0 percentage points (95% CI 19.7 to 44.4), risk ratio 4.90 (2.18–11.01); unadjusted two-proportion z-test p = <0.001.

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 Participants With Endoscopic Remission at Week 52

• 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:
  • ONTA 25mg/ONTA 25mg: 56.3% (40/71) versus 9.6% (7/73) on control; risk difference 46.7 percentage points (95% CI 33.4 to 60.1), risk ratio 5.88 (2.82–12.23); unadjusted two-proportion z-test p = <0.001.
  • ONTA 75mg/Placebo: 15.1% (13/86) versus 9.6% (7/73) on control; risk difference 5.5 percentage points (95% CI -4.6 to 15.7), risk ratio 1.58 (0.66–3.74); unadjusted two-proportion z-test p = 0.295.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for ONTA 25mg/ONTA 25mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ONTA 75mg/Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Clinical Remission at Week 52

• 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:
  • ONTA 25mg/ONTA 25mg: 67.6% (48/71) versus 17.8% (13/73) on control; risk difference 49.8 percentage points (95% CI 35.8 to 63.8), risk ratio 3.80 (2.26–6.38); unadjusted two-proportion z-test p = <0.001.
  • ONTA 75mg/Placebo: 22.1% (19/86) versus 17.8% (13/73) on control; risk difference 4.3 percentage points (95% CI -8.1 to 16.7), risk ratio 1.24 (0.66–2.34); unadjusted two-proportion z-test p = 0.502.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for ONTA 25mg/ONTA 25mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ONTA 75mg/Placebo and the control. The interval gives the range of effects that remain compatible with the data.

Number of Participants With Sustained Remission at Week 52

• 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:
  • ONTA 25mg/ONTA 25mg: 32.4% (23/71) versus 5.5% (4/73) on control; risk difference 26.9 percentage points (95% CI 14.8 to 39.0), risk ratio 5.91 (2.15–16.24); unadjusted two-proportion z-test p = <0.001.
  • ONTA 75mg/Placebo: 8.1% (7/86) versus 5.5% (4/73) on control; risk difference 2.7 percentage points (95% CI -5.1 to 10.4), risk ratio 1.49 (0.45–4.87); unadjusted two-proportion z-test p = 0.510.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the proportion with the event is statistically higher for ONTA 25mg/ONTA 25mg than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between ONTA 75mg/Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes include endoscopic remission, clinical remission, sustained remission, clinical response, mucosal healing, glucocorticoid-free outcomes, and remission based on the total Mayo score. The registry lists 12 posted secondary outcomes, but detailed arm counts and sponsor analyses are available in the analysis record for endoscopic remission, clinical remission, and sustained remission. Those outcomes generally address related aspects of disease activity or durability of remission, rather than repeating the exact primary composite.

For the outcomes with detailed results, the sponsor-reported differences in proportion favor the ontamalimab maintenance groups in both dose-level comparisons, and the reported p-values are below 0.001. These secondary findings are directionally consistent with the primary result. They are supportive context, not independent proof that every outcome or component has the same result. The endpoints differ in definition, and a participant can meet one remission definition without necessarily meeting another.

Unadjusted secondary results carry less weight when many outcomes are examined because repeated testing increases the chance of finding apparently notable results even when no true difference exists. The registry record identifies multiple outcome measures and analyses, but it does not report a multiplicity-control procedure for the secondary outcomes. Consequently, isolated secondary p-values should be interpreted cautiously and alongside endpoint definitions, effect estimates, and intervals, rather than treated as confirmatory findings.

Numerical results for the other named secondary outcomes are not reported in the registry record excerpt represented by the detailed analysis data. No conclusion about their direction or size can be drawn from their inclusion in the outcome list alone. The broad pattern in the detailed results can be described as consistent across the three secondary outcomes with numerical arm results, but it should not be generalized to all secondary endpoints without their estimates and analysis details.

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

• Number of Participants With Endoscopic Remission at Week 52
• Number of Participants With Clinical Remission at Week 52
• Number of Participants With Sustained Remission at Week 52
• Number of Participants With Clinical Response Based on Composite Score at Week 52
• Number of Participants With Mucosal Healing Based on Endoscopic and Histologic Assessment at Week 52
• Number of Participants With Glucocorticoid-free Clinical Remission at Week 52
• Number of Participants With Glucocorticoid-free Remission at Week 52
• Number of Participants With Remission Based on Total Mayo Score at Week 52

9. Statistical Interpretation

10. Statistical Methods Explained

The primary outcome is binary: each participant either met the remission definition at Week 52 or did not. The registry posts counts of participants meeting the endpoint and the group sizes used for those counts. For binary outcomes, a risk difference expresses the difference between the proportions meeting the endpoint in two groups. A positive risk difference in the stated direction means the endpoint occurred in a larger proportion of the ontamalimab maintenance group than in its placebo comparison group. The recalculated estimates are unadjusted comparisons based on the posted summaries.

What does the sponsor analysis estimate?

The registry reports sponsor analyses using the Cochran-Mantel-Haenszel method and labels the parameter as a difference in proportion. In general, this method can estimate a group difference while accounting for categorical strata. The registry record does not identify the strata or explain how the reported analysis was constructed, so those details should not be inferred. The sponsor reports a difference of 0.451 for the 25 mg comparison and 0.278 for the 75 mg comparison, each with a 95% confidence interval and p < 0.001.

The recalculated risk differences use the displayed counts and group sizes directly, without adjustment. A sponsor analysis and an unadjusted calculation can differ if their analysis populations, methods, or other inputs differ. The registry record does not explain the source of the discrepancy. Since the discrepancy flag is true, the sponsor’s own analysis takes precedence when describing the reported treatment comparisons. The recalculated estimates remain useful as a transparent check of the posted counts, but they should not be substituted for the sponsor’s stated analysis.

How should the p-values be read?

In general, a p-value describes how surprising data at least as incompatible with a null hypothesis would be if that null model and the analysis assumptions were true. It is not a measure of the size of an effect or of its practical importance, and it is not the probability that the result occurred by chance. Here, the sponsor reports p < 0.001 for each primary comparison. These values provide evidence against a null difference under the reported analysis, but the registry record does not report whether or how the primary p-values were adjusted for multiple comparisons.

The recalculated p-values are identified as unadjusted. They are based on a simple comparison of posted summary data and are not the sponsor’s adjusted or stratified analysis. No adjustment for covariates or strata is included in that recalculation. General statistical interpretation should therefore keep the source of each estimate clear rather than combining sponsor and recalculated statistics as if they were a single analysis.

What do the interval estimates add?

A confidence interval describes a range of estimates compatible with the data under a particular method and its assumptions. It shows precision as well as direction: a narrower interval generally indicates greater precision, while a wider interval leaves more uncertainty about the magnitude. The sponsor reports 95% confidence intervals. For the unadjusted recalculations, the posted estimates include lower and upper interval limits, but the registry record does not specify the confidence level or interval method for those recalculations.

General statistical caution is needed when comparing interval widths across analyses because different methods or populations can yield different intervals. An interval that excludes zero is consistent with a positive difference at its stated confidence level, but it does not establish that the difference is clinically important. The endpoint’s clinical-importance threshold is not reported in the registry record.

What does the sample-size illustration represent?

The planning illustration is based on observed effects, not the original design. It uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustrated effect to detect is a stated fraction of the observed effect. Figures for these binary outcomes are participants per arm. In general, a smaller effect requires more participants to achieve the same target power under otherwise unchanged assumptions. The original study’s sample-size calculation and its assumptions are not reported in the registry record.

Power in this planning context is the chance, under the assumed effect and model, of detecting a difference at the specified significance level. The 80% and 90% columns represent two different target probabilities in the planning calculation, not observed properties of the completed study. These figures are design illustrations and are not observed power.

General statistical concepts help explain the methods but do not fill gaps in the registry reporting. The record does not report the full statistical analysis plan, analysis-population rules for every endpoint, missing-data methods, or details of multiplicity control. Without those details, the posted estimates can be described, but the exact analysis decisions behind them cannot be reconstructed from the registry record alone.

11. Confidence Intervals and Precision

The sponsor-reported primary estimate for the 25 mg comparison is a difference in proportion of 0.451, with a 95% confidence interval from 0.296 to 0.572. For the 75 mg comparison, the sponsor-reported difference is 0.278, with a 95% confidence interval from 0.142 to 0.401. Both intervals lie above zero. The interval endpoints show that the sponsor’s analyses are compatible with a range of positive differences, not just the single point estimate.

In general, a confidence interval conveys the precision of an estimate: a wider interval indicates greater uncertainty about the magnitude. It does not give the probability that the true value lies in this specific interval, and it does not indicate whether an effect is clinically important. No threshold for a clinically meaningful difference is reported in the registry record.

The simple recalculations have their own interval limits. For the 25 mg comparison, the recalculated risk difference is 0.453, with limits of 0.321 and 0.585. For the 75 mg comparison, the recalculated estimate is 0.320, with limits of 0.197 and 0.444. The registry record does not state the confidence level or method for these recalculated intervals. They should not be confused with the sponsor’s 95% intervals, which come from the reported Cochran-Mantel-Haenszel analyses.

The discrepancy flag matters for precision as well as for the point estimates: the sponsor and recalculation do not produce identical estimates or interval limits. The sponsor’s own analysis takes precedence. Neither set of intervals captures every possible source of uncertainty, such as unreported missing-data choices or multiplicity procedures. The registry record does not report those details, so the displayed precision should be interpreted as conditional on the analysis used.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not the trial’s original design assumptions. For these binary outcomes, the figures are participants per arm, rather than total events. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect used for each planning row is the stated fraction of the observed effect. The trial’s own original sample-size justification and design assumptions are not reported in the registry record.

The 80% power column gives the planned number of participants per arm for a calculation with an 80% chance of detecting the assumed effect under those assumptions. The 90% column gives the corresponding number for a 90% chance. These are target probabilities used in planning, not probabilities that the completed study’s result is correct. This is not observed power.

Rows planning for 100%, 75%, and 50% of the observed effect illustrate how the required sample size changes when the effect assumption changes. Smaller effects need more participants to reach the same target power, because they are harder to distinguish from random variation. The estimates are conditional on the stated planning assumptions and the observed effect used as their starting point; they are not evidence that those effect sizes will recur in another study.

The figures should therefore be read as illustrations of design sensitivity, not as a retrospective verdict on whether the trial was adequately designed. The registry record does not report the original assumptions, any allowance for attrition, or the design calculation used to choose the enrollment target. No additional design assumptions should be inferred from the planning illustration.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, p₀ and p₁ are the control and treatment proportions, and p̄ is their average.

Worked calculation for this trial

1. Control proportion p₀ = 0.082; treatment proportion p₁ = 0.535; average p̄ = 0.309.
2. First term: z_1−α/2 × √[2p̄(1−p̄)] = 1.96 × 0.6533 = 1.2805.
3. Second term: z_1−β × √[p₀(1−p₀) + p₁(1−p₁)] = 0.842 × 0.5694 = 0.4792.
4. n = (1.2805 + 0.4792)² / (0.4530)² = 15.1, rounded up to 16 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 <- 0.0821917808219178                          # control proportion
p1 <- 0.535211267605634                          # 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(3290781)
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 = 16 (80% power), 20 (90% power)
 75% of observed effect: n per arm = 25 (80% power), 33 (90% power)
 50% of observed effect: n per arm = 47 (80% power), 63 (90% power)
power.prop.test: 15.1 
Simulated power at n = 16 per arm: 0.866 (20000 replicates)

The simulation draws many pairs of event counts at the planned sample size and counts how often the two-proportion z-test rejects the null. It should land close to the target power; at very small required sample sizes it can fall below it, because the normal approximation is rough there.

14. Analyses Reported by the Sponsor

The registry reports sponsor analyses for both primary dose comparisons using the Cochran-Mantel-Haenszel method. For the 25 mg comparison, the sponsor reports a difference in proportion of 0.451, with a 95% confidence interval from 0.296 to 0.572 and p < 0.001. For the 75 mg comparison, the sponsor reports 0.278, with a 95% confidence interval from 0.142 to 0.401 and p < 0.001.

The recalculated unadjusted differences from the posted counts are 0.453 and 0.320, respectively. The first recalculation is close to the sponsor estimate; the second differs more. The record flags a discrepancy between the posted summary-statistic recalculations and the sponsor’s own analysis. Its source is not reported in the registry record, so an explanation should not be assumed.

Because a discrepancy is flagged, the sponsor’s own analysis takes precedence as the reported study analysis. The unadjusted recalculation is a separate check using the posted counts, not a replacement for the sponsor analysis. Differences between the two may reflect distinctions in analytic methods or analysis inputs, but the record does not specify which, if any, account for the discrepancy. Interpret the point estimates and intervals with their analysis source kept explicit.

15. Multiplicity, Missing Data and Analysis Populations

The registry record identifies 13 outcome measures and 16 analyses, indicating that the study considered multiple results. Multiple testing matters because, as the number of statistical tests increases, the chance of at least one apparently positive result can increase even when the underlying null hypotheses are true. In general, prespecified testing hierarchies or other multiplicity procedures can address this issue, but the registry record does not report whether such a procedure was planned or used for the primary or secondary endpoints.

The two sponsor-reported primary comparisons each have p < 0.001, but the record does not state whether those p-values were adjusted for testing both dose comparisons or for any other analyses. The secondary outcomes also cover several related constructs. Without the prespecified analysis hierarchy and multiplicity method, it is not possible to determine from the registry record how strongly the secondary p-values should be treated as confirmatory.

The registry record describes the primary analysis population as the ontamalimab responder full analysis set: randomized participants who received at least one dose of study intervention and had previously been treated with ontamalimab in the induction studies. The population description is truncated in the registry record. More complete eligibility, exclusion, and analysis-population details are not reported in the registry record.

Missing-data handling is another important part of interpreting a remission endpoint that requires diary symptoms and endoscopy. The registry record does not report the imputation method, rules for incomplete assessments, sensitivity analyses, or how participants without an assessable Week 52 endpoint were treated. Those details could affect the estimated proportions and uncertainty, but their impact cannot be assessed from the reported information. The original statistical analysis plan and detailed interim-analysis information are not reported in the registry record.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: myocardial infarction (9.1%), large intestine perforation (9.1%), peritonitis (9.1%), sepsis (9.1%), joint injury (4.8%).

The registry lists serious adverse events by study arm, with the number at risk and the number affected. In ONTA 25mg/Placebo, 6 of 73 participants were affected; in ONTA 25mg/ONTA 25mg, 9 of 71; in ONTA 75mg/Placebo, 9 of 86; and in ONTA 75mg/ONTA 75mg, 2 of 82. Additional listed groups are Placebo/Placebo, with 1 of 11 affected; Placebo/ONTA 25mg, with 0 of 22; and Placebo/ONTA 75mg, with 2 of 21.

The registry reports 1 death in ONTA 75mg/Placebo and 1 in Placebo/Placebo; the other listed groups report 0 deaths. These are descriptive counts, not estimates of comparative risk adjusted for follow-up or other factors. The record’s top serious-event terms include myocardial infarction, large intestine perforation, peritonitis, and sepsis at 9.1% each, and joint injury and uterine polyp at 4.8% each. The denominator and calculation basis for those term percentages are not reported in the registry record, so they should not be interpreted as arm-specific rates.

Serious adverse event counts do not capture all safety information, and arm sizes differ. No causal attribution or comparative safety conclusion should be inferred from these counts alone. The registry record does not report further detail about event timing, duration, or adjudication in the safety information.

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

The posted results describe the proportion of analyzed participants meeting a specific remission definition at Week 52. The sponsor-reported primary analyses show positive differences in proportion for both ontamalimab maintenance comparisons with their placebo groups, with 95% confidence intervals above zero and p < 0.001. This is evidence of a difference on the defined composite endpoint under the sponsor’s reported analyses.

That statistical result does not, by itself, establish the size of benefit that matters to participants or clinicians. The registry record does not report a threshold for clinical importance. A confidence interval describes uncertainty in the estimate under the analysis assumptions; it does not resolve questions about unreported missing-data methods, multiplicity, or how broadly the findings apply. The difference between the sponsor-reported values and the simple recalculations is also relevant: the discrepancy is flagged, and the sponsor’s analysis takes precedence.

The result is specific to maintenance therapy among participants who responded in induction and to the endpoint’s symptom-and-endoscopy criteria. It should not be read as a result about initial induction treatment, all people with ulcerative colitis, or outcomes not measured at Week 52. The registry record does not report the complete primary-population description or detailed missing-data procedures, limiting assessment of the exact analysis set and robustness.

The secondary outcomes with detailed results show a direction consistent with the primary endpoint, but the record does not report a multiplicity procedure. That means the secondary findings should be interpreted as supportive rather than treated as independent confirmation for every listed outcome. Safety counts are descriptive and are not sufficient on their own for a comparative safety assessment. The trial results therefore answer a defined statistical question, while broader clinical judgments require information beyond these posted analyses.

18. Why This Trial Matters Statistically

This study illustrates several statistical issues common in multi-arm maintenance trials. The arm labels encode both induction-study treatment and maintenance assignment, so comparison groups must be identified precisely. The primary analysis compares each maintenance ontamalimab dose with a corresponding placebo group, while the posted arm data also include other treatment histories. Confusing those groups can change the interpretation of the counts.

The endpoint also illustrates how a binary composite turns several measurements into a single remission classification. Such an endpoint can be easier to interpret as a count of participants meeting defined criteria, but its meaning depends on the component rules. Here, symptoms and centrally read endoscopy are combined, and meeting every stated condition is necessary for the endpoint classification.

The comparison between sponsor analyses and unadjusted recalculations is another important lesson. The recalculated differences use posted counts directly, while the sponsor reports Cochran-Mantel-Haenszel analyses. The estimates are not identical, especially for the 75 mg comparison. Since the registry flags a discrepancy, the sponsor’s own analysis takes precedence. Reporting both without naming their methods would obscure that distinction.

Finally, multiple endpoints, missing-data methods, and analysis populations affect how strongly results can be interpreted. The record lists many outcomes but does not report the full multiplicity procedure or missing-data strategy. Those are not minor technical details: they shape uncertainty and the evidentiary role of secondary findings. The study is therefore useful for showing why effect estimates, intervals, analysis methods, and registry-reporting limits should be considered together.

19. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information reported for this trial. The primary population description is truncated, and the complete analysis-population criteria are not reported in the registry record. Although the study is described as randomized and double-blind, allocation details, masking procedures, and the randomization ratio are not reported in the registry record.

The primary endpoint combines diary-based symptoms and centrally read endoscopy, but the registry record does not report how incomplete diary records, missing endoscopies, or other missing Week 52 assessments were handled. It also does not report sensitivity analyses addressing missing data. These omissions prevent assessment of whether alternative assumptions about missing outcomes would materially change the estimates.

The record flags a discrepancy between recalculated unadjusted comparisons and sponsor-reported analyses, but does not explain its source. The sponsor analyses should take precedence, yet the absence of details about analysis populations, strata, or the full statistical method limits independent reconstruction. The original sample-size justification, multiplicity plan, interim-analysis information, and complete statistical analysis plan are not reported in the registry record.

The detailed numerical secondary results cover only a subset of the listed outcomes, and a multiplicity procedure is not reported. The safety information is presented as counts, while the denominator and calculation basis for the listed serious-event term percentages are not reported. These limits mean the posted results support a focused interpretation of the reported Week 52 endpoint, rather than a complete appraisal of all efficacy and safety questions.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: An Efficacy and Safety Study of Ontamalimab as Maintenance Therapy in Participants With Moderate to Severe Ulcerative Colitis — NCT03290781.
• Registry record last updated 2022-01-14; status last verified 2021-12.
• Results first posted 2022-01-14.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

23. Record Summary

NCT03290781 is a completed phase 3 randomized, double-blind, parallel-group, placebo-controlled study of ontamalimab maintenance therapy in participants with moderate to severe ulcerative colitis. The registry lists enrollment of 366 and Shire as sponsor. The primary outcome is remission at Week 52 based on a composite of participant-reported symptoms and centrally read endoscopy.

The sponsor reports positive differences in proportion for the 25 mg and 75 mg maintenance comparisons, with 95% confidence intervals above zero and p < 0.001 for both. The registry flags a discrepancy with unadjusted recalculations; the sponsor’s own analyses take precedence. Secondary results with detailed counts are directionally consistent, while multiplicity and missing-data methods are not reported in the registry record.