Study of Efficacy and Safety of Canakinumab in Japanese Patients With SJIA: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Efficacy and Safety of Canakinumab in Japanese Patients With SJIA (NCT02396212), a na phase 3 study. The primary outcome is Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria.

2. Clinical Question

This question combines changes in disease activity, well-being, function, joint involvement and inflammation with a fever requirement. It is a response measure rather than a direct comparison between treatment groups. The registry record identifies the endpoint and its definition but does not report the Week 8 percentage or the number of participants who met the criteria. Consequently, the record does not establish the observed degree of response or its precision.

3. Trial Design

This was a phase III, open-label, single-arm study of canakinumab in Japanese patients with systemic juvenile idiopathic arthritis. The registry reports enrollment of 19. There was no random allocation and no masking; all patients received the active study medication. Without a concurrent control group, changes during the study cannot be separated statistically from the passage of time, other influences on patient status, or assessment expectations.

Canakinumab was given at 4 mg/kg every 4 weeks by subcutaneous injection, with a maximum total single dose of 300 mg. The study was designed to provide efficacy and safety data for administration over at least 48 weeks. The registry lists the study as completed, with a start date of 2015-05-07 and a primary completion date of 2017-03-07.

The primary outcome was assessed at Week 8, earlier than the planned minimum treatment duration. Secondary outcomes include adapted ACR Pediatric response criteria over time and changes in individual components, including physician and patient or parent assessments, functional ability, active joints, joints with limited motion, fever, and standardized C-reactive protein. The registry lists 16 outcome measures. Its brief summary states that interim analysis data at Week 28 and 48 supported a registration submission in Japan; detailed interim-analysis methods and results are not reported in the registry record.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

5. Baseline Characteristics

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

Population: The Full Analysis Set (FAS) consisted of all 19 patients who were enrolled and received at least one dose of canakinumab.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants Who Achieved a Minimum Adapted American College of Rheumatology (ACR) Pediatric 30 Criteria, measured over Week 8.

The primary endpoint is the percentage of participants who achieved a minimum adapted ACR Pediatric 30 response at Week 8. The criteria define response as improvement from baseline of at least 30% in at least 3 of response variables 1 to 6, no intermittent fever in the preceding week, and no more than one variable among 1 to 6 worsening by more than 30%. The fever criterion is defined in the record as no intermittent fever due to SJIA, with temperature ≤ 38°C during the preceding week.

The response variables cover physician assessment of disease activity, patient or parent assessment of overall well-being, functional ability measured by CHAQ, active joints, joints with limitation of motion, and CRP. Combining these domains provides a rule-based summary of changes across several aspects of SJIA rather than relying on a single measure. A participant must meet the stated combination of improvement, fever, and worsening conditions to count as a responder.

As a general statistical point, a percentage endpoint is a proportion: it describes the share of the defined analysis population meeting a binary response rule. The registry record specifies the analysis population as the Full Analysis Set, but does not report the Week 8 response percentage or its uncertainty.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s primary measure is a binary response outcome. Each participant either meets the adapted ACR Pediatric 30 rule at Week 8 or does not. The group-level endpoint is the percentage meeting that rule in the Full Analysis Set. The record defines that set as all 19 patients who were enrolled and received at least one dose of canakinumab. The Week 8 responder count and percentage are not reported in the registry record.

What does a percentage endpoint represent?

As a general statistical explanation, a percentage for a binary outcome is based on the number of participants who meet the event definition relative to the participants included in the analysis. It is useful because it expresses how common the defined response was in the study group. It does not, by itself, show why the response occurred or what would have happened to the same participants under a different treatment. Here, the endpoint definition and analysis population are reported, but the observed response value is not.

A confidence interval, when reported, describes the statistical uncertainty around an estimate. For a response percentage, it would indicate a range of values compatible with the observed data under the interval’s assumptions. It would not correct for the absence of a control group, and it would not account automatically for biases or missing outcome data. No confidence interval for the primary endpoint is reported in the registry record.

Why does the composite definition matter?

The adapted ACR Pediatric 30 endpoint combines several response variables. A participant must show improvement of at least 30% in at least 3 of variables 1 to 6, have no intermittent fever in the preceding week, and avoid excessive worsening in more than one of variables 1 to 6. The variables span clinical assessment, well-being, function, joint measures and CRP. Because the endpoint is determined by the combined rule, a participant’s classification can depend on more than the direction of change in one measure. Separate component results can help describe which domains changed, but component results are not reported.

As a general consideration, composite outcomes can summarize multiple dimensions in one measure, but the components may differ in clinical meaning and measurement properties. The registry supplies the operational definition; it does not report the rationale for choosing this version of the response rule or the contribution of each component to the Week 8 result.

What can a single-arm design estimate?

A single-arm study can describe outcomes observed among participants who received the study treatment. It cannot directly estimate a between-group contrast because there is no comparator group. A before-and-after difference, if reported, would still be a within-group change, not a randomized treatment effect. General statistical explanations of causal inference emphasize that an appropriate comparison is needed to distinguish treatment effects from natural changes, co-interventions, measurement effects and other time-related influences. Those factors are not quantified in this registry record.

The study was open-label, so treatment masking is not part of the design. This matters particularly when outcomes include assessments by physicians, patients or parents. The record does not specify assessor masking or provide details about safeguards against assessment bias.

How should planning illustrations be read?

Any sample-size illustration associated with the posted results is a planning scenario, not an observed power calculation. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The stated convention is participants per arm for outcomes other than time-to-event outcomes, for which the total number of events is used. These are not the design features of this trial: the actual study had a single treatment group and no randomized comparison. A planning illustration based on two arms therefore does not describe the study’s actual allocation or establish its power.

More generally, a sample-size calculation depends on assumptions about the target effect, variability or event rate, significance level, power and allocation. It describes a hypothetical design under those assumptions. It does not measure the probability that a completed study’s result is true, and it is not a substitute for reporting the observed estimate and its uncertainty. The registry record does not report the trial’s sample-size justification or a statistical analysis plan.

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("Canakinumab 4 mg/kg Every 4 Weeks")
n      <- c(19)
events <- c(19)
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  Canakinumab 4 mg/kg Every 4 Weeks  19  19  100.0  82.4  100.0  83.2  100.0  83.2  99.9

11. Multiplicity, Missing Data and Analysis Populations

The registry record does not report how multiplicity was handled. The listed outcomes include the primary Week 8 response, adapted ACR Pediatric response measures over time, changes in several individual response components, fever and CRP. When many outcomes or assessment times are examined, the chance of at least one apparently notable result can increase if each is tested separately. As a general statistical explanation, multiplicity procedures can address that issue, but the record does not say whether any adjustment was planned or applied.

The record defines the Full Analysis Set as all 19 enrolled patients who received at least one dose of canakinumab. It does not report how many had an assessable Week 8 endpoint, how missing assessments were handled, or whether any imputation or sensitivity analysis was used. It also does not describe exclusions after enrollment, deviations from the planned treatment schedule, or analysis populations beyond the stated Full Analysis Set. Those details matter because the denominator and handling of unavailable outcome data can affect a response percentage.

The brief summary mentions interim analysis data at Week 28 and 48, but the registry record does not report the methods, decision rules, or any multiplicity adjustment related to those interim analyses. The statistical analysis plan, including prespecified hypotheses and any hierarchy among outcomes, is not reported in the registry record. The endpoint definition alone does not establish how statistical testing or missing data were handled.

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: still's disease (31.6%), histiocytosis haematophagic (15.8%), adrenal insufficiency (10.5%), pyrexia (10.5%), influenza (10.5%).

The registry reports serious adverse events for the canakinumab group with 19 participants at risk and 10 affected. For other adverse events, it reports 19 at risk and 19 affected. The reported number of deaths is 0. These are counts for the treated group, not comparisons against an untreated or active-control group.

The serious-event terms listed include Still's disease (31.6%), Histiocytosis haematophagic (15.8%), Adrenal insufficiency (10.5%), Pyrexia (10.5%), Influenza (10.5%) and Epstein-Barr virus infection (5.3%). These are the percentages attached to the listed terms in the registry record. The record does not give further detail about event timing, recurrence, duration, seriousness criteria, attribution, or the denominator used for each term percentage.

As a general statistical point, an affected-participant count indicates whether participants experienced at least one event in the category; it does not by itself describe the total number of episodes or their clinical course. With no comparison group, these figures describe reported events during the study but cannot estimate differences in risk relative to another treatment.

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

The study addresses a defined question: the percentage of participants meeting an adapted ACR Pediatric 30 response rule at Week 8 while receiving open-label canakinumab. Its response definition combines improvement in clinical, functional and inflammatory measures with conditions concerning fever and worsening. The registry record makes that endpoint interpretable as a prespecified type of outcome, but does not report its observed value.

Accordingly, the record does not show the Week 8 percentage, the number of participants meeting the criteria, or a confidence interval around the estimate. It also does not report numerical results for the listed secondary outcomes. Without those results, the registry information cannot establish the magnitude or precision of an observed response in this study.

The single-arm design permits descriptive reporting of outcomes among participants who received canakinumab, but does not provide a concurrent comparison. Any change over time in a single group could reflect more than the treatment alone. The open-label design also means that treatment assignment was known, and the registry does not report whether outcome assessors were masked. These design features limit what can be inferred even if within-group outcomes are available elsewhere.

The safety information describes adverse events in the treated group, including the reported serious-event counts, listed terms and deaths. It does not establish comparative safety. Event percentages and counts should be read as descriptions of this study’s recorded experience, not as estimates of excess risk over another treatment.

These limits do not erase the study’s descriptive role. It documents a phase III evaluation in Japanese patients, the dosing schedule, the intended minimum treatment duration, the endpoint definition and selected safety counts. But an endpoint definition is not an endpoint result, and evidence from a single treated group is not a randomized comparison. The registry record alone therefore cannot quantify a comparative treatment effect.

14. Why This Trial Matters Statistically

This trial illustrates why the study design and the outcome result must be read together. The registry defines a clinically multidimensional response at Week 8 and specifies the population for analysis. Yet a clear endpoint definition cannot answer how often response occurred when the corresponding result is not reported. Statistical interpretation requires both a well-described measure and an observed estimate with information about its precision.

The single-arm, open-label structure is also important. Results from a single group can describe the experience of participants receiving treatment, but they do not supply the counterfactual comparison needed to estimate how outcomes would differ under another treatment. This is a design limitation, not something that can be resolved by a more elaborate interpretation of the same group’s response percentage.

The response rule highlights another general issue: a composite endpoint can bring several disease dimensions into one outcome, while obscuring which dimensions drove an overall response. Reporting component outcomes alongside the composite can help clarify that pattern. The registry lists component-related outcomes, but does not provide their numerical results.

Finally, the safety record distinguishes serious from other adverse events and reports deaths separately. Those categories are useful for describing the recorded experience, but without a comparator they cannot establish relative risk. The study is therefore statistically informative as a description of its design, definitions and reported safety counts, while its registry record does not give the primary efficacy result or a comparative treatment estimate.

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 principal limitation for interpreting efficacy from the registry record is that it does not report the primary endpoint result. The Week 8 response percentage, responder count and uncertainty are absent, as are numerical results for the listed secondary outcomes. The record therefore allows the outcome definition to be described but not the observed efficacy estimate to be assessed.

The study had no control group and was open-label. Without a comparator, the results cannot isolate treatment-associated change from other changes over time. Knowledge of treatment may also influence subjective assessments; the registry does not report whether outcome assessors were masked or describe procedures to limit assessment bias.

The registry defines the Full Analysis Set, but does not report missing-data handling, the number of participants with evaluable Week 8 data, or sensitivity analyses. It does not provide a statistical analysis plan, multiplicity approach, or sample-size justification. The brief summary mentions interim analysis data at Week 28 and 48, but detailed methods and results for those analyses are not reported in the registry record.

The enrollment was 19, so estimates from this study would be based on a limited group of participants. As a general statistical point, estimates from a small group can be imprecise, and the degree of precision should be judged using reported uncertainty measures; no primary-endpoint confidence interval is reported. The record also does not provide detailed event-level safety information, including timing, recurrence or attribution. These limitations are specific to interpreting the registry information and do not establish what may be available in other records.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Efficacy and Safety of Canakinumab in Japanese Patients With SJIA — NCT02396212.
• Registry record last updated 2019-09-13; status last verified 2019-08.
• Results first posted 2019-09-13.
• 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

NCT02396212 is a completed phase III, open-label, single-arm study of canakinumab in Japanese patients with systemic juvenile idiopathic arthritis. The registry reports enrollment of 19 and treatment with canakinumab 4 mg/kg every 4 weeks, with a maximum total single dose of 300 mg. The study was designed to provide efficacy and safety data for treatment lasting at least 48 weeks.

The primary endpoint was the percentage meeting minimum adapted ACR Pediatric 30 criteria at Week 8. The Full Analysis Set consisted of all enrolled patients who received at least one dose. The primary result and numerical secondary outcome results are not reported in the registry record. Safety listings report 10 participants affected by serious adverse events among 19 at risk, 19 affected by other adverse events among 19 at risk, and 0 deaths. The record does not provide a concurrent control group or a comparative treatment estimate.