An Open Label Safety and Tolerability Study of AIN457 in Patients With Moderate to Severe Crohn's Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open Label Safety and Tolerability Study of AIN457 in Patients With Moderate to Severe Crohn's Disease (NCT01009281), a na phase 2 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

The question is descriptive rather than comparative. With one group and no masking, the record can describe events among participants who received study drug, but it cannot estimate a treatment difference against a control group. The stated population also matters: participants entered the extension after completing a core trial, so the study concerns that selected group rather than all people with Crohn's disease.

The registry lists secondary outcomes involving anti-AIN457 antibodies, interleukin 17, fecal calprotectin and lactoferrin, C-reactive protein, and drug concentrations. Their outcome values are not reported in the registry record. The primary adverse-event outcome value is also not reported in the registry record, so the clinical question is specified but its posted primary result cannot be assessed from this record.

3. Trial Design

This is a phase 2, single-group, open-label extension study of AIN457 in participants with moderate to severe Crohn's disease. Its stated purpose was to assess safety and tolerability in people who had already participated in and completed the core trial CAIN457A2202. Enrollment was 7. The record lists no allocation scheme and no masking.

The study title describes a 52-week open-label extension. The primary endpoint timeframe is separately described as running from study start to study termination, up to 42 weeks. These descriptions are both present in the registry record; a reason for the different durations is not reported in the registry record. The study start date is 2009-10-30 and the primary completion date is 2010-08-19. Its status is terminated. The reason for termination is not reported in the registry record.

A single-group extension can collect follow-up safety observations in participants who entered the extension, but it does not provide a randomized or concurrent control for separating study-period events from events that might otherwise occur. Open-label status means masking was not used. The record does not report additional design details such as the dosing schedule, eligibility thresholds beyond the stated disease severity and prior core-trial participation, or the planned duration of individual follow-up beyond the endpoint timeframe.

The intervention is named AIN457, while the adverse-event group is labeled Secukinumab. The record does not explain this difference in naming. It should therefore be retained as a feature of the registry labels rather than used to infer additional design details. No sample-size justification or rationale for the enrollment target is 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: A total of 7 participants enrolled in the study. All seven participants were discontinued due to early termination of the core study (CAIN457A2202 \[NCT00584740\]) due to lack of efficacy.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set consisted of all participants who received at least one dose of study drug.

5. Baseline Characteristics

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

Population: Safety analysis set consisted of all participants who received at least one dose of study drug.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over From Start of the Study up to Study Termination (up to 42 Weeks).

The primary endpoint is the number of participants with adverse events. It is a participant count, not a measure of how many total events occurred. The stated timeframe runs from study start to study termination, up to 42 weeks. The safety analysis set includes participants who received at least one dose of study drug.

Safety outcomes are used to describe unwanted events observed during exposure and follow-up. A participant count can indicate how many people experienced an event, but by itself does not describe the event's severity, duration, recurrence, or relationship to study treatment. Those details require their own reported measures and definitions. A count also depends on the population included and the period during which events are captured.

The primary endpoint's numerical result is not reported in the registry record. The adverse-event summary contains counts for serious and other categories, but it does not supply a result for the stated primary endpoint as a whole. Consequently, the listed information does not establish how many participants experienced any adverse event under the primary endpoint definition. The record also does not provide the endpoint's operational definition for what qualified as an adverse event or explain how the relationship of an event to study drug was assessed.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

General statistical explanation: A single-group safety study primarily describes what was observed in the enrolled group. A participant count answers how many people met an outcome definition, but it is not equivalent to an event rate over person-time, a count of repeated events, or a comparison between treatments. Those different summaries require different data and definitions.

In this record, the primary outcome is a count of participants with adverse events. The analysis population is defined as all participants who received at least one dose. This is an exposure-based safety population: participants are included because they received study drug, rather than because they completed every planned visit. However, the registry does not report the numerical result for this primary outcome, and it does not report how many participants were included in the actual primary analysis.

General statistical explanation: A confidence interval expresses uncertainty around an estimate under the assumptions of the method used. For a participant count or proportion, an interval can convey that the observed count is only one realization from a broader range of plausible underlying experiences. A count of 0 does not imply that the underlying probability is exactly 0; the uncertainty depends on the amount and structure of the data. No confidence intervals for the adverse-event counts are reported in the registry record, so the precision of those counts cannot be quantified from the posted results.

Comparative analyses require a meaningful comparison. Here, the design is listed as single-group, allocation is not applicable, and masking is none. There is no concurrent control arm in the design information. Consequently, a treatment contrast, a between-arm standard error, and a comparative p-value cannot be derived from the listed design. The counts should not be interpreted as evidence of superiority, equivalence, or non-inferiority.

General statistical explanation: In a randomized trial, allocation can make treatment groups comparable on average at the start of follow-up, while masking can reduce some forms of assessment or reporting influence. Neither feature is present as a comparison framework in this single-group open-label extension. That does not invalidate a descriptive safety count, but it limits what can be concluded from the count about effects attributable to treatment.

The registry describes a range of secondary outcome types. Antibody status is a participant-level outcome; biomarker and drug-concentration outcomes may be expressed as changes or concentrations. Each kind of outcome can require different summaries and assumptions. The names of these measures alone do not establish what statistical model was planned, how measurements over time were handled, or how missing observations were treated. Those details are not reported in the registry record, and numerical results for the secondary outcomes are not reported in the registry record.

General statistical explanation: Over-dispersion matters when count data vary more than a model's assumed distribution allows. In such settings, a model that assumes too little variability may produce confidence intervals that are too narrow or tests that are too optimistic. That consideration is relevant to analyses of event counts, especially when repeated events per participant are modeled, but the primary endpoint is a count of participants, and no model for repeated event counts is described. The registry does not report a statistical model or an over-dispersion assessment.

Planning calculations and observed results answer different questions. A sample-size calculation uses assumptions about the effect to detect, the significance level, allocation, and a statistical method; it describes a planning scenario, not the result observed in a trial. The record does not report a sample-size justification or the assumptions used by the study team. It also does not report a protocol-based power calculation. The observed enrollment of 7 should therefore be treated as the enrollment count, not as evidence that the study had a particular probability of detecting an effect.

The registry record lists no analysis entries. It does not describe a prespecified analysis plan, a model for the primary endpoint, a method for estimating uncertainty, or rules for handling multiple outcomes. No inferential result should be reconstructed from the event counts alone. In particular, a p-value would not supply a missing treatment comparison in a design with no control group, and a post hoc calculation would not replace the sponsor's own analysis if one were reported.

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("Secukinumab")
n      <- c(7)
events <- c(3)
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  Secukinumab  7  3  42.9  9.9  81.6  15.8  75.0  15.7  75.5

11. Multiplicity, Missing Data and Analysis Populations

The record names a primary outcome and several secondary outcomes. It does not report how the study team planned to control multiplicity across those outcomes, whether any outcome hierarchy was used, or whether formal hypothesis tests were planned. No analysis entries are listed. It is therefore not possible to determine from the registry record whether multiplicity adjustment was planned or applied. The secondary measures should be read as listed outcomes, not as a collection of confirmed statistical findings.

Missing-data handling is not reported in the registry record. The record does not explain whether participants with incomplete follow-up contributed to the primary safety summary, how missed visits were treated, or how missing biomarker or concentration measurements were handled. For a safety outcome, the exposure-based analysis-set definition identifies who may be eligible for inclusion, but it does not itself explain how incomplete observation time or missing event information was addressed.

The safety analysis set is defined as participants who received at least one dose of study drug. The registry does not report the number analyzed for each outcome or clarify whether all enrolled participants received a dose. It also does not describe exclusions, protocol deviations, or any alternative analysis population. These omissions limit assessment of whether the analysis population matches the enrolled group and whether follow-up was complete.

Because the endpoint values and analysis details are incomplete, no adjustment for multiplicity or missingness can be independently assessed. The reported event counts can be stated descriptively, but they should not be extended into claims about unreported outcomes or analyses.

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 5% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summary lists 0 serious adverse events among 7 participants at risk in the group labeled Secukinumab. The other adverse-event category lists 3 participants affected among 7 at risk. The summary also lists 0 deaths, and no top serious-event terms are listed. These are the safety counts reported in the registry record; the primary endpoint result itself is not reported in the registry record.

Counts of participants should not be confused with counts of individual events. One participant could experience more than one event, but the summary does not provide event totals or details needed to determine recurrence. The record also does not give event descriptions for the other category, so its clinical character cannot be inferred from the count alone.

A count of 0 serious events in this group does not establish that serious events cannot occur. The small number of participants limits how precisely the observation characterizes experience beyond those enrolled. No confidence interval is reported. The design has no comparison group, so these counts cannot show whether serious or other events were more or less frequent than under another condition. The registry also does not explain the difference between the AIN457 intervention name and the Secukinumab adverse-event group label.

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

The posted information establishes the basic design and a small set of descriptive safety observations. It identifies a phase 2 open-label extension, a single-group design, enrollment of 7, an endpoint focused on participants with adverse events, and the observed serious-event, other-event, and death counts. It also identifies the safety population as participants who received at least one dose.

Those details do not establish a causal effect. Without a concurrent comparator, events cannot be contrasted with what would have occurred under another treatment or without study treatment. The open-label design and the prior participation requirement also define the context in which the observations were collected; the findings concern the extension's participants and should not automatically be generalized to a broader population.

The reported 0 serious adverse events and 0 deaths describe observations in the recorded group. They do not demonstrate that the risk of such events is absent. Similarly, the 3 participants in the other adverse-event category do not establish severity, attribution, or a treatment-related mechanism. The registry does not report enough event detail to answer those questions.

The primary outcome is specified but its numerical result is not reported in the registry record. Numerical results for the listed secondary outcomes are also not reported in the registry record. Thus, the record does not permit a complete evaluation of its stated safety objective, nor does it support interpretation of biomarker, immunogenicity, or pharmacokinetic findings.

The appropriate reading is consequently narrow: retain the listed counts as descriptive observations, recognize the small single-group context, and distinguish reported data from unanswered questions. The record does not support a conclusion about comparative safety, efficacy, or the overall benefit-risk profile.

14. Why This Trial Matters Statistically

This trial illustrates how an outcome can be clearly named while the result needed to answer the stated question is absent. The primary endpoint is the number of participants with adverse events, but that result is not reported in the registry record. A statistical interpretation therefore begins by separating the endpoint definition from the outcome data actually available.

Its single-group structure also demonstrates why descriptive safety data and comparative evidence are different. A count can document observed events in a group, but without a comparator it cannot quantify a treatment difference. The open-label design and enrollment from a previously completed core trial further define a specific follow-up setting rather than a general population sample.

The record emphasizes the importance of population and follow-up definitions. The primary endpoint is limited to a stated timeframe of up to 42 weeks, while the official title describes a 52-week extension. The record does not reconcile those descriptions. The safety analysis population is exposure-based, but the number actually analyzed is not separately stated.

Finally, the record shows why reporting uncertainty, missing-data procedures, and analysis plans matters. Counts alone do not show their precision, and outcome names do not reveal how results were analyzed. Without the primary result, analysis entries, or details of missingness and multiplicity, readers must keep interpretation descriptive and avoid filling gaps with assumptions.

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 are specific to the record and design. Enrollment was 7, and the study used a single-group, open-label structure without a concurrent comparator. This permits description of observed events but not a controlled estimate of a treatment difference. The listed serious-event and death counts are small-group observations, and no uncertainty intervals are reported in the registry record.

The study status is terminated, but the reason for termination is not reported in the registry record. The official title describes a 52-week extension, whereas the primary endpoint timeframe says up to 42 weeks. The record does not explain the relationship between these durations or whether termination altered planned follow-up.

The primary endpoint result is not reported in the registry record, and results for the listed secondary outcomes are not reported in the registry record. The record lists no analysis entries. It does not describe the planned statistical methods, missing-data procedures, multiplicity approach, sample-size justification, or event-assessment procedures. Consequently, important aspects of the design and analysis cannot be evaluated.

The participants had completed a core trial before entering the extension. This makes the enrolled group a selected follow-up population, and the record does not provide information that would support generalizing its observations to all people with moderate to severe Crohn's disease. The adverse-event group label is Secukinumab while the intervention is named AIN457; the registry does not explain the naming difference. These limitations counsel against interpreting the listed counts beyond their descriptive scope.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open Label Safety and Tolerability Study of AIN457 in Patients With Moderate to Severe Crohn's Disease — NCT01009281.
• Registry record last updated 2021-07-12; status last verified 2021-06.
• Results first posted 2021-07-12.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT01009281 is a phase 2, open-label, single-group extension study of AIN457 in participants with moderate to severe Crohn's disease who had completed core trial CAIN457A2202. Enrollment was 7, allocation was not applicable, and masking was none. The study is marked terminated; the reason is not reported in the registry record.

The primary outcome is the number of participants with adverse events, in a safety analysis set defined by receipt of at least one dose. Its stated timeframe is up to 42 weeks. The registry reports 0 serious adverse events among 7 at risk, 3 participants affected in the other adverse-event category among 7 at risk, and 0 deaths. The primary endpoint result and secondary outcome results are not reported in the registry record. With no concurrent comparator and no listed analysis entries, the reported counts are descriptive and do not establish comparative effects.