This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for 38 Week Extension Study to CAIN457C2303 (NCT01093846), a randomized phase 3 study. The primary outcome is The Effect of Continuous Treatment With Subcutaneous AIN457 Compared to Placebo in Reducing the Rate of Recurrent Ocular Exacerbations in Behçet's Patients With Intermediate Uveitis, Posterior Uveitis or Panuveitis in Group 1..
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01093846 |
| Phase | Phase 3 |
| Condition | Uveitis |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 59 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Patients with Behçet's disease and intermediate uveitis, posterior uveitis or panuveitis who completed the core study and continued treatment in the extension study, identified as Group 1. The broader study description focuses on posterior or panuveitis. The registry record does not report further eligibility details or characteristics of the participants included in this group.
Intervention
Continuous subcutaneous AIN457, with listed treatment groups receiving 300 mg every 2 weeks or 300 mg monthly. Treatment was adjunctive to standard-of-care immunosuppressive therapy. Further details about treatment delivery or adherence are not reported in the registry record.
Comparator
Placebo, also described as placebo AIN457, alongside standard-of-care immunosuppressive therapy. The record lists a placebo arm but does not give further details about the placebo regimen or concomitant therapy.
Primary question
Among Group 1 participants, did continuous subcutaneous AIN457 compared with placebo reduce the rate of recurrent ocular exacerbations during the stated 62-week timeframe? The extension’s planned comparison was not completed: the registry record says the study ended early and no efficacy analyses were completed. Therefore, the posted results do not answer the primary question.
3. Trial Design
This was a phase 3, randomized, double-masked, parallel-group study listed as a 38-week extension to CAIN457C2303. The parent study is described as a 24 week multicenter, randomized, double-masked, placebo-controlled study. The extension concerned patients with Behçet's disease and uveitis, and compared AIN457 with placebo as adjuncts to standard-of-care immunosuppressive therapy.
The record lists AIN457 300 mg every 2 weeks, AIN457 300 mg monthly, and placebo as the treatment groups. It identifies random allocation and double masking, but does not report the allocation ratio, the randomization procedure, or who was masked. It also does not report the sites or the details of how standard-of-care treatment was managed across groups.
Enrollment is listed as 59. The study began in 2010-03, has a primary completion date of 2011-01, and is marked terminated. The primary outcome timeframe is 62 weeks. The registry record does not explain the relationship between that timeframe and the 38-week extension description, nor does it report when or why termination occurred beyond stating that early termination changed the planned extension analysis.
The trial’s extension objective was to assess recurrent ocular exacerbations among Group 1 participants who completed the core study and continued treatment. Because no efficacy analyses were completed, the randomized design alone does not provide an estimated treatment contrast in the posted results. Safety information is listed separately.
4. Participant Flow and Accounting
The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.
Overall Study
| Stage | AIN457 300 mg Every 2 Weeks | AIN457 300 mg Monthly | AIN457 Placebo |
|---|---|---|---|
| STARTED | 19 | 18 | 22 |
| COMPLETED | 0 | 0 | 1 |
| NOT COMPLETED | 19 | 18 | 21 |
Reasons for not completing this period:
| Reason | AIN457 300 mg Every 2 Weeks | AIN457 300 mg Monthly | AIN457 Placebo |
|---|---|---|---|
| Adverse Event | 0 | 0 | 1 |
| Lack of Efficacy | 0 | 0 | 4 |
| Condition no longer required study drug | 1 | 1 | 1 |
| Administrative Problems | 18 | 17 | 15 |
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.
| Characteristic | Unit | AIN457 300 mg Every 2 Weeks | AIN457 300 mg Monthly | AIN457 Placebo | Total |
|---|---|---|---|---|---|
| Participants analysed | 19 | 18 | 22 | 59 | |
| Age, Continuous | years | 36.5 (SD 10.01) | 36.8 (SD 13.07) | 34.9 (SD 11.20) | 36.0 (SD 11.29) |
| Sex: Female, Male: Female | Participants | 6 | 5 | 11 | 22 |
| Sex: Female, Male: Male | Participants | 13 | 13 | 11 | 37 |
6. Primary Endpoint
The registry lists the primary outcome as The Effect of Continuous Treatment With Subcutaneous AIN457 Compared to Placebo in Reducing the Rate of Recurrent Ocular Exacerbations in Behçet's Patients With Intermediate Uveitis, Posterior Uveitis or Panuveitis in Group 1., measured over 62 weeks.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The stated primary endpoint concerns the rate of recurrent ocular exacerbations in Behçet's patients with intermediate uveitis, posterior uveitis or panuveitis in Group 1. It asks whether continuous subcutaneous AIN457, compared with placebo, reduces the rate over the 62-week timeframe. The target population is specifically described as people who completed the core study and continued into the extension.
A recurrent-event rate is intended to capture repeated episodes rather than only whether a participant experiences any episode. As a general statistical concept, this can be useful when episodes may occur more than once and the number of episodes is clinically relevant. Interpreting such a rate requires clear definitions of an exacerbation, the time participants contribute to observation, and how incomplete follow-up is handled. Those operational definitions and analysis details are not reported in the registry record.
The outcome entry gives no unit, parameter or dispersion measure. More importantly, the registry record states that early termination changed the extension-period analysis and that no efficacy analyses were completed. It therefore contains no posted estimate of the primary endpoint, no comparison between treatment groups, and no measure of uncertainty for the proposed treatment effect.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a randomized comparison of two AIN457 dosing schedules with placebo, but it does not provide an efficacy result for the primary question. Its outcome description explicitly says that early termination changed the planned extension analysis and that no efficacy analyses were completed. There is consequently no posted estimate of the recurrent ocular exacerbation rate, no treatment contrast, and no confidence interval or p-value for efficacy.
This absence is not evidence that the groups had the same outcome, nor does it establish that AIN457 reduced or increased exacerbations. The direction and size of any efficacy difference cannot be determined from the record. The randomized design is relevant to how a completed comparison might be interpreted, but randomization does not substitute for an outcome analysis.
The posted safety summary lists 39 participants at risk in each of the AIN457 300mg Every 2 Weeks, AIN457 300mg Monthly, and Placebo groups. Serious adverse events affected 7, 8, and 5 participants, respectively. These are counts within the listed safety groups; the record does not provide an efficacy comparison or a statistical analysis of these safety counts. It also lists other adverse events affecting 28, 27, and 25 participants, respectively, but those counts should not be confused with the serious-event counts.
Among the listed serious adverse event terms, folliculitis is shown as 5.1%. Supraventricular tachycardia, vertigo, cataract cortical (Fellow eye), cataract nuclear (Fellow eye), and cataract subcapsular (Fellow eye) are each shown as 2.6%. The record does not identify the treatment group for each term in this list or give additional comparisons for these events. Death counts are not reported in the registry record.
Enrollment is listed as 59, while the safety group entries each list 39 at risk. The registry record does not explain how these figures relate to one another or describe the analysis populations in enough detail to reconcile them. The figures should therefore be read as separate entries with their stated contexts, not combined into an inferred participant flow. Overall, the posted record supports a description of the study design and selected safety counts, but not an estimate of efficacy or a conclusive comparative safety assessment.
9. Statistical Methods Explained
The methods information in the registry record is limited. It identifies a randomized, double-masked, parallel-group phase 3 study and describes the intended primary outcome, but it does not report a completed efficacy analysis. Statistical concepts can help explain what the planned comparison would have addressed, while keeping the distinction clear between general methods and methods actually documented for this study.
What does randomization contribute?
As a general principle, random allocation is intended to make treatment groups comparable, on average, with respect to both measured and unmeasured baseline characteristics. This supports a fair comparison when outcomes are analyzed according to the assigned groups and follow-up is handled appropriately. The record confirms randomization, but does not describe the allocation sequence, concealment procedures, allocation ratio or analysis population. It is therefore not possible to assess those implementation details from the registry entry.
What does double masking mean?
In general, masking is intended to reduce the influence of knowledge about treatment assignment on participant experience, clinical management, outcome assessment or reporting. The record labels the study double-masked but does not specify which roles were masked, how masking was maintained, or whether masking was assessed. Those details should not be inferred from the label alone.
How should a recurrent-event rate be understood?
In general, a recurrent-event outcome counts repeated episodes over a period of observation. A rate relates the event count to the time participants were observed, which can differ across people if follow-up is incomplete or varies in duration. The endpoint in this study is described as the rate of recurrent ocular exacerbations, but the registry entry does not state the exact event definition, the rate denominator, how time at risk was determined, or how events were verified.
General models for recurrent counts may account for differences in observation time and for extra variability between participants. Over-dispersion is a general statistical concern: it occurs when outcome counts vary more than a simple count model expects, and failure to account for it can make uncertainty estimates too narrow. This does not establish that over-dispersion occurred in this trial or that any particular model was used. The statistical model, its assumptions and any adjustment factors are not reported in the registry record.
What would an estimate and confidence interval show?
In general, an effect estimate would describe the observed contrast between treatment groups on the prespecified scale. A confidence interval would express the statistical uncertainty around that estimate: a wider interval indicates less precision, while a narrower interval indicates greater precision under the analysis assumptions. A p-value, when reported, addresses compatibility between the data and a specified null hypothesis under a chosen statistical procedure; it does not measure the size or clinical importance of an effect. None of these efficacy statistics is posted for the primary endpoint, because no efficacy analyses were completed.
What can be said about sample size and power?
The registry record lists enrollment as 59, but does not report a sample-size justification or a planned power calculation. It also provides no observed primary efficacy effect from which an effect-based planning illustration could be anchored. Any hypothetical sample-size calculation would depend on assumptions about the target effect, event rates, variability, follow-up and analysis method. Those assumptions cannot be reconstructed from the posted efficacy results, and the enrollment figure should not be interpreted as evidence of achieved or observed power.
What does early termination change?
Early termination is important because the registry says the extension-period analysis was changed and no efficacy analyses were completed. The record does not describe the timing or reason for termination in further detail, any interim analysis, or the statistical plan before and after the change. Without that information, it is not possible to assess whether the planned analysis was modified in other ways or whether any available data could have supported an efficacy estimate. The appropriate statistical reading is limited: the efficacy question was stated, but an efficacy result is absent from the posted record.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a statistical analysis plan for multiplicity, missing data or analysis populations. The stated primary objective concerns recurrent ocular exacerbations in Group 1, and the record lists multiple treatment groups, but it does not say how comparisons between the two AIN457 schedules and placebo would have been prioritized or adjusted for multiple testing. It would be inappropriate to assume that a particular comparison was primary for inferential purposes beyond the wording of the objective, or that a multiplicity procedure was used.
Missing-data methods are also not reported. The record does not describe the extent or timing of missing outcome observations, participant withdrawals, incomplete follow-up, censoring, or any imputation or sensitivity analyses. These details matter in general because incomplete observation can affect recurrent-event counts and the time contributing to a rate. The registry entry does not provide enough information to evaluate the direction or size of any such effects.
The analysis populations are not described beyond the endpoint’s reference to Group 1 participants who completed the core study and continued treatment in the extension. The record does not say whether efficacy analyses were planned by randomized assignment, treatment received, or another population definition. It also does not explain how the safety groups relate to the enrollment entry of 59. Since no efficacy analyses were completed, there are no posted analysis-population results to compare.
In general, a prespecified multiplicity strategy, explicit missing-data methods and clear population definitions help readers understand how much confidence to place in results. Here, the central issue is more basic: there are no efficacy results to interpret, and the relevant analysis details are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| AIN457 300mg Every 2 Weeks | 7 | 39 | 17.9% |
| AIN457 300mg Monthly | 8 | 39 | 20.5% |
| Placebo | 5 | 39 | 12.8% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| AIN457 300mg Every 2 Weeks | 28 of 39 |
| AIN457 300mg Monthly | 27 of 39 |
| Placebo | 25 of 39 |
Most frequent serious adverse event terms
| Event term | Organ system | AIN457 300mg Every 2 Weeks | AIN457 300mg Monthly | Placebo |
|---|---|---|---|---|
| Uveitis (Fellow eye) | Eye disorders | 1 of 39 | 1 of 39 | 0 of 39 |
| Uveitis (Study eye) | Eye disorders | 0 of 39 | 1 of 39 | 1 of 39 |
| Folliculitis | Infections and infestations | 2 of 39 | 0 of 39 | 0 of 39 |
| Supraventricular tachycardia | Cardiac disorders | 1 of 39 | 0 of 39 | 0 of 39 |
| Vertigo | Ear and labyrinth disorders | 0 of 39 | 1 of 39 | 0 of 39 |
| Cataract cortical (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
| Cataract nuclear (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
| Cataract subcapsular (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
| Choroiditis (Fellow eye) | Eye disorders | 1 of 39 | 0 of 39 | 0 of 39 |
| Glaucoma (Fellow eye) | Eye disorders | 0 of 39 | 0 of 39 | 1 of 39 |
Most frequent non-serious adverse event terms
| Event term | Organ system | AIN457 300mg Every 2 Weeks | AIN457 300mg Monthly | Placebo |
|---|---|---|---|---|
| Headache | Nervous system disorders | 9 of 39 | 7 of 39 | 10 of 39 |
| Pyrexia | General disorders | 6 of 39 | 3 of 39 | 4 of 39 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 4 of 39 | 3 of 39 | 3 of 39 |
| Nausea | Gastrointestinal disorders | 4 of 39 | 3 of 39 | 2 of 39 |
| Upper respiratory tract infection | Infections and infestations | 3 of 39 | 5 of 39 | 1 of 39 |
| Fatigue | General disorders | 2 of 39 | 2 of 39 | 4 of 39 |
| Vision blurred (Fellow eye) | Eye disorders | 0 of 39 | 6 of 39 | 1 of 39 |
| Visual acuity reduced (Study eye) | Eye disorders | 4 of 39 | 2 of 39 | 1 of 39 |
| Abdominal pain upper | Gastrointestinal disorders | 3 of 39 | 3 of 39 | 1 of 39 |
| Aphthous stomatitis | Gastrointestinal disorders | 3 of 39 | 2 of 39 | 2 of 39 |
Serious events with the highest arm-level rate: folliculitis (5.1%), supraventricular tachycardia (2.6%), vertigo (2.6%), cataract cortical (fellow eye) (2.6%), cataract nuclear (fellow eye) (2.6%).
The safety entries list 39 participants at risk in each group: AIN457 300mg Every 2 Weeks, AIN457 300mg Monthly and Placebo. The serious adverse event counts are 7, 8 and 5, respectively. The entries for other adverse events are 28, 27 and 25, respectively. These are counts as posted; the registry record does not provide confidence intervals or a statistical comparison for them.
The serious-event terms listed include folliculitis at 5.1%, and supraventricular tachycardia, vertigo, cataract cortical (Fellow eye), cataract nuclear (Fellow eye), and cataract subcapsular (Fellow eye), each at 2.6%. The record does not identify a treatment group alongside each term, so these percentages should not be assigned to an arm. The basis for the percentages and the event-specific participant counts are not further detailed in the entry.
Deaths are not reported in the registry record. The listed safety denominators and counts should be kept separate from the enrollment figure of 59, since the record does not explain their relationship. These entries describe reported safety information; they do not establish a comparative safety effect.
12. What the Result Does, and Does Not, Mean
The record establishes that a phase 3 randomized, double-masked extension study was intended to compare two AIN457 schedules with placebo for recurrent ocular exacerbations in Behçet's patients with uveitis. The endpoint focused on Group 1 participants who completed the core study and continued in the extension. The record also indicates that the study was terminated and that early termination changed the extension analysis.
The key interpretive point is that no efficacy analyses were completed. There is no posted estimate of the primary endpoint, no treatment contrast, and no uncertainty interval. The clinical question therefore remains unanswered by the posted efficacy results. The absence of an estimate must not be treated as evidence of no difference, evidence of benefit, or evidence of harm.
The safety portion contains group-level counts for serious and other adverse events, along with a list of selected serious adverse event terms and percentages. Those entries permit a limited description of the reported events, but the registry does not provide statistical comparisons, event-term group assignments, or a fuller account of follow-up and analysis populations. They cannot resolve the efficacy question and should not be converted into a claim about the comparative safety of the treatments.
More generally, a trial’s design and its results are distinct. Randomization and masking describe planned safeguards for a comparison; they do not supply an outcome estimate when the analysis was not completed. The record is informative about the study’s intended objective, treatment groups, status and some safety reporting, but it does not support a numerical conclusion about whether the treatments differed on recurrent ocular exacerbations.
13. Why This Trial Matters Statistically
This study is statistically important as an example of the distinction between a carefully described research question and an available estimate addressing that question. The registry identifies a randomized, double-masked, parallel-group extension and states a recurrent-event objective, yet reports that early termination changed the analysis and that no efficacy analyses were completed. Readers can learn what the trial intended to compare without having a result from which to judge the size or precision of the intended contrast.
The endpoint also highlights a common design and analysis challenge. Recurrent events are not equivalent to a single yes-or-no outcome: repeated episodes and time under observation may both matter. As a general statistical matter, a clear event definition, a specified approach to time at risk, and suitable methods for repeated counts are necessary for an interpretable rate comparison. Those details are not reported in the registry record, so no particular analytic approach should be attributed to this study.
The safety entries demonstrate a separate interpretive boundary. Group counts and selected event percentages describe what is posted, but without documented analysis populations, event-term group assignments and comparative uncertainty, they do not establish a treatment contrast. Keeping descriptive reporting separate from inferential conclusions is essential, particularly when the primary efficacy analysis is absent.
Finally, the record shows why transparency about termination and analysis changes matters. It says that the extension analysis changed, but gives no further details about the reason, timing or statistical consequences. That information would help readers assess what questions the available data could address. In its absence, the defensible statistical conclusion is limited to the design and reported safety entries, not an efficacy claim.
14. 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 most important trial-specific limitation is that the registry record reports no completed efficacy analyses after early termination. As a result, the primary endpoint has no posted estimate, treatment comparison, confidence interval or p-value. The planned question about recurrent ocular exacerbations cannot be answered from the efficacy information in the record.
The record gives limited detail about the endpoint itself. It does not specify the operational definition of an ocular exacerbation, the event-counting rules, the denominator for the rate, or the method for handling varying follow-up. It also does not report the statistical model, prespecified contrasts or adjustment strategy. These omissions limit the ability to assess how a completed efficacy analysis would have been constructed.
Important study-process information is not reported in the registry record, including the reason and timing of termination, any interim analyses, a sample-size justification, missing-data methods and analysis-population definitions. The stated 62-week timeframe appears alongside a 38-week extension description, but the record does not explain their relationship. Enrollment is listed as 59, while each safety group lists 39 at risk; the record does not explain the relationship between these figures.
The safety reporting is also limited for comparative interpretation. Although group-level counts and selected serious-event terms are listed, the record does not provide event-specific treatment assignments for the listed terms or comparative uncertainty estimates. Death counts are not reported in the registry record. These limitations do not alter what the entries state, but they restrict conclusions about efficacy and comparative safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: 38 Week Extension Study to CAIN457C2303 — NCT01093846.
- Registry record last updated 2016-02-22; status last verified 2016-01.
- Results first posted 2016-02-22.
- 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.
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18. Record Summary
NCT01093846 is listed as a phase 3, randomized, double-masked, parallel-group extension study, titled 38 Week Extension Study to CAIN457C2303. It concerned AIN457 and placebo as adjuncts to standard-of-care immunosuppressive therapy for Behçet's patients with uveitis. The listed AIN457 regimens were 300 mg every 2 weeks and 300 mg monthly.
Enrollment is listed as 59. The study began in 2010-03, has a primary completion date of 2011-01, and is marked terminated. Its primary objective concerned the rate of recurrent ocular exacerbations in Group 1 over 62 weeks. The registry record states that early termination changed the extension analysis and that no efficacy analyses were completed.
Safety entries list 39 participants at risk in each group, with serious adverse event counts of 7, 8 and 5. The posted record therefore describes the intended comparison and selected safety information, but contains no efficacy estimate for the primary question.