Safety and Tolerability of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Safety and Tolerability of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis (NCT01109940), a na phase 2 study. The primary outcome is Number of Participants Reported Adverse Events (AE's).

2. Clinical Question

This is a safety-focused question, not a randomized test of treatment efficacy. The registry summary says the extension was intended to provide continuous treatment to patients from the core trial and obtain safety and tolerability information. Although the summary also mentions evaluating efficacy, the named primary outcome is the number of participants reported to have adverse events. The registry record does not report a primary efficacy outcome result or an analysis comparing AIN457 with a randomized control.

3. Trial Design

This was a Phase 2, open-label, non-randomized extension study of AIN457 in patients with moderate to severe ankylosing spondylitis. The registry lists an enrollment of 39 and identifies the sponsor as Novartis Pharmaceuticals. The study started in 2010-04, reached primary completion in 2012-12, and is marked completed.

The registry describes the intervention as AIN457A, a biological intervention, and refers to AIN457 in the study summary. Treatment was given by intravenous infusion at 3 mg/kg every 4 weeks. The summary describes Part 1 as an initial period of up to 6 months. It then states that a decision was made to continue dosing for another 6-month period, based on the risk/benefit balance of AIN457 in ankylosing spondylitis. The primary outcome timeframe is from study start up to 64 weeks.

As an extension, the study was designed around continued treatment for patients in the core trial, rather than enrollment into a randomized comparison described in the registry. The study is explicitly identified as non-randomized and open label, with no masking. These design features mean that the named groups should not be treated as if they were assigned comparable treatment arms in a randomized trial. The registry includes a Placebo/Secukinumab group label, but does not establish that group as a randomized control for the other groups.

The registry record does not report the rationale for the enrollment target, detailed eligibility criteria, or further allocation procedures. It also does not report an analysis plan that would clarify how comparisons between groups were intended to be handled. The reported design supports descriptive reading of the safety counts, with caution about comparisons and causal conclusions.

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 39 participants enrolled in the study of which 28 completed the study and 11 discontinued the study. Few participants were enrolled into the extension study (CAIN457A2209E1 \[NCT01109940\]) prior to completion of the core study (CAIN457A2209 \[NCT00809159\]).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety analysis set.

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 Reported Adverse Events (AE's), measured over From start of the study up to 64 weeks.

The primary endpoint is the number of participants reported to have adverse events, measured in participants in the safety analysis set. Its timeframe runs from the start of the study up to 64 weeks. The registry definition includes any unfavorable and unintended diagnosis, symptom, sign, syndrome or disease that occurs during the study after being absent at baseline, or that worsens if already present at baseline.

A participant count is a straightforward way to describe how many people experienced at least one event meeting the endpoint definition. It can provide a broad account of the frequency of reported safety events in the studied group. However, a count does not by itself convey the event’s severity, duration, timing, relatedness to treatment, or whether a participant experienced more than one event. Those details require separate outcome definitions or analyses.

The record names the endpoint but does not report an overall result for it or a statistical analysis of the primary endpoint. The serious and other adverse-event figures reported by group offer related safety information, but they should not be mistaken for a complete result for the named primary endpoint. In particular, the registry does not report a single overall count for all participants with any adverse event under the primary definition.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies the study as Phase 2, open label, non-randomized, and single group, while also listing several safety groups. It names the primary outcome as a participant count and specifies the safety analysis set as its population. It does not report a statistical analysis plan or a primary-outcome analysis. The distinction matters: design labels and descriptive counts do not establish which statistical procedures were planned or used.

What a participant count conveys

In general, a participant count records how many people meet an event definition during a stated observation period. It is useful for describing the observed safety experience, especially when the endpoint is explicitly defined. For this study, the adverse-event definition encompasses new unfavorable diagnoses, symptoms, signs, syndromes or diseases, as well as worsening of conditions present at baseline. A count does not describe how many separate events occurred if a participant had repeated events, and it does not encode event severity or duration unless those are reported separately.

The registry’s group-level safety figures distinguish participants at risk from participants affected for serious and other adverse events. That presentation permits a reader to identify the reported counts within each group. It does not, by itself, provide a statistical comparison between groups. A comparison would need to account for the design and the basis on which participants entered each group. The registry explicitly warns that the arms are not a like-for-like control comparison.

Why randomization matters for comparisons

In general, random assignment helps make treatment groups comparable at the start of a trial, on average, by limiting systematic differences in how participants are allocated. Without randomization, differences in observed outcomes may reflect group composition, prior treatment, follow-up, or other factors as well as treatment. This study is described as a non-randomized extension for patients in a core trial, so group-level differences should be read descriptively. The registry record does not report an adjustment strategy that would address potential differences between groups.

Open-label status means the study is not masked. In general, knowledge of treatment assignment can influence reporting, assessment, or decisions about whether a symptom is recorded as an event. This does not show that such influence occurred in this study; the record does not report an assessment of that possibility. It is a design consideration when interpreting reported adverse events.

Uncertainty and precision

In general, a confidence interval gives a range of values compatible with an estimate under a specified statistical method and assumptions. It can communicate precision more fully than a point estimate alone. No confidence intervals for the safety counts or group comparisons are reported in the registry record. Nor does the record report hypothesis tests or p-values for those comparisons. Without such estimates, the posted counts do not quantify statistical uncertainty beyond showing how many participants were recorded in each category.

Small group counts can make estimates imprecise, and a count of zero events does not establish that the underlying chance of an event is zero. That general point is relevant to reading groups with no serious adverse events reported, but it does not justify calculating an unreported risk estimate. The registry record does not report inferential estimates for these groups.

Planning calculations versus trial results

In general, sample-size planning calculations use assumptions about an effect, variability, significance level, allocation, and target power to illustrate how much information a future study might need. They are not observed outcomes and do not demonstrate that a completed study had a particular power. Planning illustrations based on an observed effect are especially dependent on the chosen effect fraction and assumptions. The record does not report the trial’s own sample-size justification, and any planning illustration should not be interpreted as an analysis result or as observed power.

The registry record does not report the statistical methods used to analyze the primary endpoint, any model for repeated events, an approach to account for varying observation time, or a method for handling possible over-dispersion. In general, over-dispersion occurs when count data vary more than a chosen model expects; ignoring it can make uncertainty estimates too small. That is a general modeling issue, not evidence that a particular model or problem applied to this study.

Finally, the record lists secondary outcomes related to antibodies and blood or serum concentrations, but does not report analyses for them. No estimate should be inferred from the outcome names alone. The available information supports a cautious descriptive reading of the reported safety counts rather than a claim about inferential or comparative findings.

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("Dose Group 1", "Dose Group 2", "Dose Group 3", "Secukinumab/Placebo")
n      <- c(21, 8, 7, 3)
events <- c(21, 6, 6, 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  Dose Group 1  21  21  100.0  83.9  100.0  84.5  100.0  84.6  99.9
ARM  Dose Group 2  8  6  75.0  34.9  96.8  40.9  92.9  40.0  92.5
ARM  Dose Group 3  7  6  85.7  42.1  99.6  48.7  97.4  47.3  96.8
ARM  Secukinumab/Placebo  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary adverse-event outcome and four named secondary outcomes concerning antibodies for secukinumab, total interleukin-17A concentration in blood, and peak and trough serum observations at steady state. The record does not report a multiplicity plan describing whether or how statistical testing across outcomes was controlled. It also does not report a hierarchy of tests or a prespecified approach to interpreting multiple comparisons. Because no outcome analyses are reported, the record does not show how multiplicity may have affected any conclusions.

Missing-data methods are not reported in the registry record. It does not describe how incomplete outcome observations, withdrawals, or missing assessments were handled, nor does it report follow-up completeness by group. The listed number at risk is relevant context for each safety group, but does not alone explain whether all participants had the same observation time or whether any outcome information was missing.

The primary outcome population is identified as the safety analysis set. The record does not further define that set or report other analysis populations, such as an intention-to-treat or per-protocol population. It also does not say how participants were assigned to the listed safety groups or explain the relationship between those groups and treatment exposure in enough detail for a comparative analysis. These omissions limit interpretation of both the group counts and the scope of the reported safety experience.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: folliculitis (12.5%), staphylococcal abscess (12.5%), crohn's disease (4.8%), sinusitis (4.8%), arthritis (4.8%).

The serious adverse-event figures are participant counts reported within each group, with the number at risk stated alongside the number affected. Dose Group-1 reports 4 of 21 participants at risk with serious adverse events; Dose Group-2 reports 1 of 8; Dose Group-3 reports 0 of 7; and Placebo/Secukinumab reports 0 of 3. The record reports 0 deaths in each group.

The term list includes Folliculitis and Staphylococcal abscess at 12.5% each, and Crohn's disease, Sinusitis, Arthritis and Depression at 4.8% each. These are registry-reported percentages. The record does not state their denominator or provide additional context such as timing, severity grading, or whether the events were judged related to treatment. They should not be interpreted as comparative rates across groups.

In general, serious adverse events are distinct from the broader category of other adverse events, but a participant count does not summarize the full clinical detail of each event. The groups were not randomized like-for-like controls, so their counts are descriptive and do not establish that a treatment caused or prevented an event.

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

The posted safety figures describe the number of participants reported with serious and other adverse events within each listed group. They also show 0 deaths reported in each group. Alongside those counts, the registry provides selected serious adverse-event terms and percentages. The record does not report an overall result for the named primary endpoint or a statistical comparison of groups.

These data do not establish that AIN457 caused an adverse event, prevented one, or changed the chance of an event compared with a control. The study was open label and non-randomized, and the registry cautions that the groups are not a like-for-like control comparison. Differences in counts therefore cannot be interpreted as treatment effects. The data also do not establish that no serious events occurred beyond the recorded observation or that an event absent from the listed terms never occurred.

The record describes the study as an extension for patients in the core trial and gives a primary outcome timeframe from study start up to 64 weeks. It does not report the completeness of follow-up, an overall count for all participants with any adverse event under the primary definition, or event-level details sufficient to assess severity, timing, or relatedness. The outcome names for antibodies and drug concentration measurements likewise do not establish any result for those measures.

In general, safety counts are most informative when read together with their event definitions, observation period, analysis population, and uncertainty estimates. Here, the population is named as the safety analysis set and the timeframe is stated, but methods for missing data and statistical uncertainty are not reported in the registry record. The findings should therefore be understood as descriptive registry entries from this extension study, not as a randomized estimate of benefit or harm and not as medical advice.

14. Why This Trial Matters Statistically

This study illustrates why the design behind a safety count is essential to its interpretation. The registry reports counts for several groups, but identifies the study as a non-randomized extension and cautions that the groups are not comparable like randomized arms. A numerical difference between groups can be described, but without a suitable design and analysis it should not be assigned a causal explanation.

The record also highlights the importance of matching an endpoint label to the results actually reported. The named primary endpoint is the number of participants with adverse events, yet the record does not report an overall result or analysis for that endpoint. Group-level serious and other adverse-event counts are useful descriptive information, but they do not replace a full report of the primary outcome or its analysis.

Safety outcomes require clear definitions and context. The registry defines adverse events broadly and states the observation timeframe, while also listing selected serious event terms. However, it does not report all details needed to interpret those terms, such as event-level timing, severity grading, or relatedness. A participant count, a term-specific percentage, and a formal comparative estimate answer different statistical questions.

Finally, the record shows why reporting analysis populations, missing-data methods, uncertainty estimates, and multiplicity plans matters. Without those details, readers can describe what was recorded but cannot assess the precision or robustness of an inferential conclusion. This is particularly important for an extension study in which treatment continuation and group membership are not described as randomized comparisons.

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.

The main limitation for interpretation is the non-randomized, open-label design. The registry explicitly warns that the listed groups are not a like-for-like control comparison. Group-level safety differences therefore cannot establish treatment effects, and open-label status may be relevant to how events were reported or assessed. The record does not report methods to address those design limitations.

The study is described as an extension for patients in the core trial, so its population is not presented as an independently randomized sample. The registry does not provide detailed eligibility criteria or describe how participants entered each listed group. Enrollment was 39, and the group counts at risk range across the listed groups; small counts make descriptive patterns especially sensitive to individual observations.

Outcome reporting is incomplete for statistical interpretation. The record names the primary adverse-event endpoint but does not report its overall result or an analysis. It does not provide confidence intervals, hypothesis tests, adjusted estimates, or a method for handling missing data. Follow-up completeness and event-level details are also not reported. For the serious adverse-event term percentages, the denominator is not stated in the registry record.

The registry names secondary measures but does not report their results. It also does not report the trial’s sample-size justification, a multiplicity strategy, or a statistical analysis plan. These gaps prevent assessment of how outcomes were selected, how uncertainty was quantified, or whether the reported safety summaries represent complete follow-up. The available information is therefore best treated as descriptive registry reporting rather than a basis for comparative or causal conclusions.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Safety and Tolerability of AIN457 in Adults (18-65 Years) With Moderate to Severe Ankylosing Spondylitis — NCT01109940.
• Registry record last updated 2021-06-24; status last verified 2021-06.
• Results first posted 2021-06-24.
• 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 Phase 2 study was an open-label, non-randomized extension of AIN457 treatment in adults with moderate to severe ankylosing spondylitis. The registry lists enrollment of 39, a study start in 2010-04, and primary completion in 2012-12. Treatment was described as intravenous AIN457 at 3 mg/kg every 4 weeks, with an initial period of up to 6 months and a further 6-month period after a decision to continue dosing.

The primary outcome was the number of participants reported with adverse events in the safety analysis set, from study start up to 64 weeks. The record provides group-level serious and other adverse-event counts, selected serious adverse-event terms, and death counts, but no overall primary-outcome analysis. It cautions that groups are not like-for-like controls. Statistical analysis methods, missing-data methods, and a sample-size justification are not reported in the registry record.