Study of Safety, Tolerability, and Efficacy of Ustekinumab for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Safety, Tolerability, and Efficacy of Ustekinumab for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency (NCT02199496), a non-randomized phase 1, phase 2 study. The primary outcome is Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Single Dose Administration of Ustekinumab.

2. Clinical Question

This is a safety-focused question in a rare and clinically specific population. The study also had an efficacy objective, but the primary endpoint described in the registry is a count of participants with an increase in infection or serious adverse events. The registry lists 3 outcome measures and no analysis records. Consequently, the posted information does not provide a complete statistical answer to either the primary safety question or the broader efficacy objective.

3. Trial Design

This was an open-label Phase I/II pilot study sponsored by the National Institute of Allergy and Infectious Diseases (NIAID). The registry lists a non-randomized allocation, no masking, a parallel model, and enrollment of 5. The study status is completed. Its listed start date is 2015-10-19, and its primary completion date is 2019-08-16.

The registry describes three cohort labels: Cohort 1 single-dose Phase 1, Cohort 1 multi-dose Phase 2, and Cohort 2 multi-dose Phase 2. The single-dose Phase 1 description says participants received an induction dose of 270 mg ustekinumab subcutaneously. It also says participants were re-enrolled into a multi-dose phase. The Cohort 2 multi-dose description says participants received a 270 mg subcutaneous induction dose, followed by 90 mg subcutaneous maintenance doses every 8 weeks at week 8, week 16, week 24, week 32, and week 40. The description for Cohort 1’s multi-dose regimen is cut off in the registry record, so its full schedule is not reported in the registry record.

Without random assignment or masking, treatment groups should not be treated as balanced comparison arms. Cohort membership may be related to study phase and treatment exposure, and the registry does not describe a randomized procedure for making those groups comparable. In addition, the single-dose cohort description includes re-enrollment, so the group labels do not necessarily represent independent sets of people. The registry does not provide enough information to reconstruct individual participant movement across cohorts.

The enrollment figure and the adverse-event groups’ at-risk counts do not align as a simple set of distinct participants. The registry record does not report a reconciliation of those figures. This makes it important to read each adverse-event count within its listed cohort and not combine cohorts or assume that every cohort count represents a different participant.

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.

Ustekinumab-Single Dose

Ustekinumab-Multi-dose

Analysis population for the primary outcome, as defined in the registry: Participants who received ustekinumab

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 Number of Participants With Increase in Infection or Serious Adverse Events (SAEs) Related to Single Dose Administration of Ustekinumab, measured over 6 months.

The primary endpoint is the number of participants with an increase in infection or serious adverse events related to single-dose ustekinumab. It is expressed as a count of participants, and the stated timeframe is 6 months. Its description frames the endpoint as a safety and tolerability assessment in participants with CVID enteropathy, with attention to infection and serious adverse events.

A participant count is a straightforward way to report how many people in a defined group experienced the specified outcome. It can make an important safety signal visible without implying that all events have the same clinical meaning. The outcome definition matters: this endpoint concerns an increase in infection or serious adverse events related to single-dose administration, not every adverse event and not efficacy. The registry’s general adverse-event summaries list serious and other adverse events by cohort, but the registry record does not report a numerical result for the primary endpoint as defined.

That distinction limits interpretation. The serious-event counts are not automatically equivalent to the primary endpoint because the primary endpoint specifies an increase, a relation to single-dose administration, and a 6 months timeframe. The registry record does not provide the endpoint’s participant-level definition, a baseline comparison for determining an increase, or an endpoint result count. These details are not reported in the registry record.

For a count endpoint, the number of participants at risk and the rules used to identify and attribute events are central to interpretation. The posted cohort-specific at-risk counts are small, and no comparative control group is identified. The endpoint may describe observed safety experience, but the registry information does not establish a comparative treatment effect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The record describes a Phase I/II pilot study with non-randomized allocation, no masking, and a parallel model. The posted outcome summaries are counts of participants with events. No outcome analyses are listed. This means the available statistical interpretation rests on descriptive counts rather than a reported model-based or randomized comparison.

What does a participant count tell the reader?

A count identifies how many participants in a specified group met an event definition. It is most informative when the group size, event definition, follow-up period, and ascertainment method are also clear. The registry provides cohort-specific at-risk counts and counts affected for serious and other adverse events. The primary endpoint, however, has no numerical result reported in the registry record. Its count therefore cannot be interpreted from the event summaries alone.

Counts are not the same as event totals. One participant may experience more than one event, while a participant-level count records whether that participant met the outcome definition. A count also does not reveal the timing, duration, recurrence, or clinical course of events. Those details are not reported in the registry record in the registry record for this analysis.

Why does the non-randomized design matter?

General statistical explanation: randomization helps make groups comparable, on average, with respect to both measured and unmeasured characteristics. In a non-randomized study, group differences can reflect who entered each group, changes in study phase, differences in exposure, or other factors, in addition to any treatment effect. Because this study was not randomized and had no masking, cohort-specific adverse-event counts should be interpreted descriptively, not as a controlled estimate of comparative risk.

The cohort structure also complicates simple comparisons. The Cohort 1 single-dose description says participants were re-enrolled into the multi-dose phase. As a result, a participant may be represented in more than one cohort description. The record does not report participant-level linkage or a flow accounting that would establish whether group counts overlap. The listed enrollment of 5 and at-risk counts across cohort summaries should not be added together as though they necessarily represent unique people.

What do the sample-size illustrations mean?

The planning illustration is described as using the observed effect, a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It considers the effect to detect as a stated fraction of the observed effect. These are planning assumptions, not a description of the trial’s actual design. The record does not report the trial’s own sample-size justification, and the study itself was non-randomized rather than an equal-allocation, two-arm randomized comparison.

General statistical explanation: a sample-size calculation estimates how many participants a proposed study might require under chosen assumptions about the effect, variability, significance threshold, and analysis. Such a calculation is conditional on those assumptions. It is not a measure of the probability that this completed study found a true effect. A planning illustration based on an observed effect should not be read as observed power, and the record does not report a trial-specific sample-size rationale.

The registry entries do not include numerical sample-size illustration results, so no required participant count can be stated. The planning framework also does not address whether the observed effect is a suitable target for a future study. That decision would require a defensible effect assumption and a design suited to the research question; those are not reported in the registry record.

How should uncertainty be understood?

General statistical explanation: a confidence interval gives a range of values that are reasonably compatible with observed data under a specified statistical method and its assumptions. Narrower intervals generally indicate greater precision, while wider intervals indicate more uncertainty. Small groups with uncommon events often produce imprecise estimates, and a zero observed count does not establish that the underlying event risk is zero.

No confidence intervals, hypothesis tests, adjusted estimates, or analysis methods for the listed safety outcomes are reported in the registry record. The record lists 0 analyses. Thus, there is no reported inferential result with which to quantify uncertainty around the observed counts. Descriptive counts remain useful for documenting what was recorded, but they cannot substitute for an estimate with uncertainty or a valid causal comparison.

What can be inferred from event categories?

Serious adverse events and other adverse events are separate summaries. The serious-event terms include percentages, but the available record does not state enough about denominators or overlap to convert them into participant counts or compare them reliably across groups. A percentage for an event term is not itself a comparative effect measure. The registry also does not report a treatment-relatedness breakdown for the listed terms, except that the primary endpoint description refers to events related to single-dose administration.

General statistical explanation: when multiple outcomes or event categories are examined, the chance of finding an apparently unusual result can rise if many tests are conducted. Methods for addressing multiplicity depend on the analysis plan and the intended claims. No multiplicity procedure or statistical analysis plan is reported in the registry record. Since the record lists 3 outcome measures but no analyses, it is not possible to determine whether multiplicity was considered or how any outcome hierarchy was applied.

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("Cohort 1: Ustekinumab-Single Dose Phase 1")
n      <- c(3)
events <- c(0)
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  Cohort 1: Ustekinumab-Single Dose Phase 1  3  0  0.0  0.0  70.8  0.0  56.1  0.6  60.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 3 outcome measures and no analyses. It does not report an analysis plan, a hierarchy among outcomes, or a procedure for handling multiple comparisons. The primary endpoint is described as a participant count concerning an increase in infection or serious adverse events related to single-dose administration over 6 months, but a numerical result for that endpoint is not reported in the registry record. The record also does not report inferential results for the other outcome measures in the registry record for this analysis.

General statistical explanation: multiplicity arises when several outcomes, groups, time points, or statistical tests are examined. Without a prespecified plan, it can be difficult to distinguish a primary confirmatory question from exploratory observations. Adjustments can be used to control error rates across a set of tests, but whether they are appropriate depends on the planned claims and analysis. No adjustment method is reported in the registry record, so none can be attributed to this study.

Missing-data handling is not reported in the registry record. The available information does not describe the number of participants with missing endpoint data, how incomplete follow-up was handled, or whether an imputation method was used. Analysis populations are also not defined beyond the primary endpoint’s description of participants who received ustekinumab. The registry does not report whether the outcome summaries use all enrolled participants, participants who received treatment, or another analysis set.

These omissions matter because safety counts depend on who was observed and for how long. If follow-up or event reporting differs across participants or cohorts, counts may not represent comparable observation. The registry record does not provide enough detail to evaluate those possibilities or to reconstruct the analysis population.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: gastritis (50.0%), respiratory syncytial virus infection (50.0%), neuropathy peripheral (33.3%).

The serious adverse-event summaries are cohort-specific: 0 of 3 participants in Cohort 1 single-dose Phase 1, 1 of 3 in Cohort 1 multi-dose Phase 2, and 2 of 2 in Cohort 2 multi-dose Phase 2 were listed as affected. The registry lists 0 deaths in each cohort. These are descriptive counts from the posted results, not estimates from a randomized comparison.

The record also lists other adverse events affecting 3 of 3 participants in each of the first two cohorts and 2 of 2 in the third. These counts should not be confused with the serious-event counts. The listed serious-event terms are Gastritis at 50.0%, Respiratory syncytial virus infection at 50.0%, and Neuropathy peripheral at 33.3%. The available record does not specify the denominators and overlap needed to interpret those percentages as distinct participant counts.

The primary endpoint concerns an increase in infection or serious adverse events related to single-dose administration during 6 months. The adverse-event summaries do not provide the endpoint’s numerical result or enough information to establish an increase from a baseline. They also do not show whether each event was judged related to treatment. Small at-risk groups, possible cohort overlap through re-enrollment, and the absence of randomization all limit comparisons. The counts document recorded events; on their own, they do not establish cause, comparative risk, or the frequency expected in a broader population.

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

The posted information describes a completed, open-label Phase I/II pilot study of ustekinumab in people with CVID-associated gastrointestinal inflammation. Its design and size make the reported adverse-event counts descriptive. The record gives cohort-specific counts of participants affected by serious and other adverse events, along with a count of deaths. It does not provide a numerical result for the primary endpoint as defined, or a statistical analysis of that endpoint.

The counts show that serious adverse events were recorded in the multi-dose cohorts and none were listed for the single-dose Phase 1 cohort. This is a description of the registry’s cohort summaries, not evidence that dose schedule caused a difference. The cohorts were not randomized, the study was unmasked, and Cohort 1’s description includes re-enrollment into a multi-dose phase. The record does not establish that the cohorts were independent or comparable.

The result does not provide a precise estimate of risk in the wider CVID population. The at-risk groups are small, the registry does not report uncertainty intervals for the event summaries, and the record does not give a full account of follow-up or missing data. The listed event-term percentages also cannot be interpreted as population rates without clear denominators and overlap information.

The registry’s primary question is narrower than a general inventory of adverse events: it concerns an increase in infection or serious adverse events related to single-dose administration during 6 months. That endpoint result is not reported in the registry record. The available counts therefore cannot settle the stated primary safety question. The broader efficacy objective is also not answered by the safety summaries, and a numerical efficacy result is not reported in the available information.

None of these limitations means that the observations have no value. Pilot safety data can describe what was recorded and identify questions that may warrant clearer evaluation in a larger, appropriately designed study. However, these posted results do not establish that ustekinumab works or does not work, nor do they establish that the recorded events were caused by treatment. They are best read as limited, cohort-level safety observations with substantial uncertainty.

14. Why This Trial Matters Statistically

This trial is statistically notable because it studies a specific population with CVID-associated gastrointestinal inflammation in a Phase I/II pilot setting. For a small, uncommon population, a pilot can document treatment exposure and observed safety events. The registry’s cohort descriptions and adverse-event counts provide that kind of descriptive information, while also showing why the design must guide interpretation.

The central statistical issue is the gap between the primary endpoint and the results reported in the record. The endpoint is defined around an increase in infection or serious adverse events related to single-dose administration over 6 months, yet no numerical result for that endpoint is reported. The general adverse-event counts cannot be assumed to answer it. Clear endpoint reporting is necessary to connect the study objective with the observed data.

A second issue is the cohort structure. The study was non-randomized and open-label, and the single-dose cohort description includes re-enrollment into a multi-dose phase. These features make simple arm-to-arm comparisons unsuitable and raise questions about overlap among cohort summaries. The registry does not report a participant-flow account that resolves these questions. This is a useful reminder that counts need to be interpreted in the context of who was counted, under what exposure, and during what follow-up.

Finally, the record illustrates the difference between descriptive evidence and statistical inference. Counts and event terms can communicate what was recorded, but without a reported analysis plan, uncertainty estimates, or complete outcome results, they do not quantify precision or support a causal conclusion. Statistical reporting is especially important when groups are small, since each participant’s outcome can have a large influence on the observed summary. The study’s information is therefore relevant as pilot safety documentation, while its limits leave the primary question unresolved in the registry record.

15. 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 arise from the specific registry information. Enrollment is listed as 5, while the cohort summaries list at-risk counts of 3, 3, and 2. Those figures are not reconciled in the registry record. Because the Cohort 1 single-dose description says participants were re-enrolled into a multi-dose phase, cohort counts may not represent independent groups. The record does not provide a participant flow or linkage that would clarify this.

The study was non-randomized, open-label, and had no masking. It therefore lacks a randomized, masked control comparison for interpreting differences in adverse events. The cohort labels also reflect different phases and treatment schedules, making direct comparisons difficult. The description of the Cohort 1 multi-dose schedule is incomplete in the registry record.

The primary endpoint result is not reported in the registry record, despite the endpoint being identified as a participant count over 6 months. The available safety summaries do not state whether each event was treatment-related, how an increase was defined, or how the endpoint was assessed against baseline. The record does not report confidence intervals, hypothesis tests, or analysis methods for these outcomes.

Additional details needed to assess completeness are not reported in the registry record, including missing-data handling, analysis populations, outcome ascertainment procedures, and a statistical analysis plan. The serious-event term percentages are listed without enough information in the available record to establish their denominators or overlap. These limitations constrain both the precision of safety interpretation and any attempt to generalize beyond the listed participants.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Safety, Tolerability, and Efficacy of Ustekinumab for Symptomatic Gastrointestinal Inflammation Associated With Common Variable Immunodeficiency — NCT02199496.
• Registry record last updated 2020-08-24; status last verified 2020-07.
• Results first posted 2020-08-24.
• 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.

19. Record Summary

This completed study evaluated ustekinumab for symptomatic gastrointestinal inflammation associated with common variable immunodeficiency. It was an open-label Phase I/II pilot with non-randomized allocation, no masking, a parallel model, and enrollment of 5. The registry lists 3 outcome measures and no analyses.

The primary endpoint concerned the number of participants with an increase in infection or serious adverse events related to single-dose administration over 6 months. Its numerical result is not reported in the registry record. Cohort-specific summaries list serious adverse events in 0 of 3, 1 of 3, and 2 of 2 participants, with 0 deaths in each cohort. Other adverse events were listed for all participants at risk in each cohort. The results are descriptive and cannot support a randomized comparison or a precise estimate of risk. The registry does not report enough information to reconcile cohort counts, establish participant overlap, or evaluate missing data and outcome analyses.