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 An Open-label Extension Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis and Active Systemic Manifestations Manifestations and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever. (NCT00891046), a na phase 3 study. The primary outcome is Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00891046 |
| Phase | Phase 3 |
| Condition | Systemic Juvenile Idiopathic Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 270 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
Participants with systemic juvenile idiopathic arthritis (SJIA), including people previously responsive to canakinumab and treatment-naïve participants with active SJIA with or without fever. The safety analysis included participants who received at least one dose of study drug.
Intervention
Canakinumab, described in the study summary as 4 mg/kg subcutaneously every 4 weeks. Participants who were steroid-free could taper to 2 mg/kg subcutaneously every 4 weeks.
Comparator
No randomized control group is reported. The record distinguishes participants previously treated with ACZ885 from ACZ885 treatment-naïve participants, but these groups are not a like-for-like randomized comparison.
Primary question
How many participants experienced adverse events, serious adverse events, events by severity, events leading to discontinuation, or events considered treatment-related during the study and follow-up?
The study also tracked response and other clinical outcomes, including ACR Pediatric response levels, steroid tapering, clinical remission, disability, well-being, pain, and health-related quality of life. Those outcomes describe additional questions the study was intended to address; the registry record does not provide results for them in the registry record for this analysis.
The principal result is descriptive safety information from two participant groups. It should be read as a record of events observed during follow-up, not as an estimate of what would have happened under a different treatment. Because the allocation is listed as not applicable and the study model is single-group, the group labels do not create a randomized treatment contrast.
3. Trial Design
This is a phase 3, open-label extension study of canakinumab in participants with SJIA and active systemic manifestations. Its official title describes two populations: participants who took part in earlier studies and participants who were canakinumab treatment-naïve, with active SJIA with or without fever. The study record lists an enrollment of 270 and a completed status.
The study summary describes retreatment with canakinumab at 4 mg/kg subcutaneously every 4 weeks. Participants who were steroid-free could taper the dose to 2 mg/kg subcutaneously every 4 weeks. Follow-up was to continue until discontinuation or until study CACZ885G2402 was in place at the participant’s study center, or around March 2013, whichever occurred first. The registry record lists the study start as 2009-09 and primary completion as 2014-12.
The safety results distinguish ACZ885-treated participants from ACZ885 treatment-naïve participants. These are descriptive groups rather than treatment arms assigned by randomization: allocation is listed as not applicable, masking as none, and the model as single-group. The registry record does not describe a concurrent control group.
The primary outcome concerns adverse events and serious adverse events from Day 1 through the end of follow-up. The stated endpoint timeframe differs by group: through Week 271 for ACZ885-treated participants and through Week 145 for ACZ885 treatment-naïve participants. These different follow-up limits matter when reading event counts because the groups did not have the same stated observation window. The registry record does not report participant-level follow-up durations or exposure-adjusted event rates.
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 147 participants from studies CACZ885G2301 (NCT number: NCT00889863) and CACZ885G2305 (NCT number: NCT00886769) and 123 canakinumab treatment- naive participants were enrolled into this extension study.
Overall Study
| Stage | ACZ885 Treated: Group 1 (Discontinued From Core Study) | ACZ885 Treated: Group 2 (Completed Core Study) | ACZ885 Treated: Group 3 (Steroid Taper Failures in Core Study) | ACZ885 Treated: Group 4 (Other Criteria) | ACZ885 Treatment Naive |
|---|---|---|---|---|---|
| STARTED | 33 | 63 | 40 | 11 | 123 |
| COMPLETED | 21 | 54 | 17 | 8 | 84 |
| NOT COMPLETED | 12 | 9 | 23 | 3 | 39 |
Reasons for not completing this period:
| Reason | ACZ885 Treated: Group 1 (Discontinued From Core Study) | ACZ885 Treated: Group 2 (Completed Core Study) | ACZ885 Treated: Group 3 (Steroid Taper Failures in Core Study) | ACZ885 Treated: Group 4 (Other Criteria) | ACZ885 Treatment Naive |
|---|---|---|---|---|---|
| Protocol Violation | 1 | 1 | 0 | 0 | 1 |
| Unsatisfactory therapeutic effect | 5 | 2 | 19 | 2 | 20 |
| Administrative problems | 0 | 0 | 0 | 0 | 1 |
| Participant no longer required drug | 0 | 2 | 0 | 0 | 1 |
| Adverse Event | 4 | 3 | 2 | 0 | 14 |
| Withdrawal by Subject | 2 | 1 | 2 | 1 | 1 |
| Lost to Follow-up | 0 | 0 | 0 | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The analysis was performed in safety set (SS), defined as 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 Set: The analysis was performed in safety set (SAF), defined as all participants who received at least one dose of study drug.
| Characteristic | Unit | ACZ885 Treated: Group 1 (Discontinued From Core Study) | ACZ885 Treated: Group 2 (Completed Core Study) | ACZ885 Treated: Group 3 (Steroid Taper Failures in Core Study) | ACZ885 Treated: Group 4 (Other Criteria) | ACZ885 Treatment Naive | Total |
|---|---|---|---|---|---|---|---|
| Participants analysed | 33 | 63 | 40 | 11 | 123 | 270 | |
| Age, Customized: 2 -- <4 years | participants | 0 | 2 | 3 | 1 | 18 | 24 |
| Age, Customized: 4 -- <6 years | participants | 6 | 10 | 6 | 5 | 15 | 42 |
| Age, Customized: 6 -- <12 years | participants | 16 | 32 | 21 | 3 | 50 | 122 |
| Age, Customized: 12 -- <20 years | participants | 11 | 17 | 10 | 2 | 40 | 80 |
| Age, Customized: ≥ 20 years | participants | 0 | 2 | 0 | 0 | 0 | 2 |
| Sex: Female, Male: Female | Participants | 19 | 34 | 23 | 5 | 75 | 156 |
| Sex: Female, Male: Male | Participants | 14 | 29 | 17 | 6 | 48 | 114 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), AEs by Severity, AEs Leading to Discontinuation, SAEs Leading to Discontinuation, Treatment Related AEs and SAE, measured over From start of study treatment (Day 1) up to end of follow-up period (Week 271 for ACZ885 treated participants and Week 145 for ACZ885 treatment naive participants).
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is a set of participant counts covering adverse events (AEs), serious adverse events (SAEs), AEs by severity, events leading to discontinuation, SAEs leading to discontinuation, and treatment-related AEs and SAEs. An AE is defined in the record as an unfavorable and unintended sign, symptom, or disease temporally associated with study-drug use, whether or not it was considered related to the drug. An SAE is defined by specified consequences, including death or a life-threatening event, hospitalization, significant or permanent disability, congenital anomaly or birth defect, or another clinically significant event that could jeopardize a participant or require intervention to prevent such outcomes.
Treatment relationship was based on the investigator’s judgment that an AE or SAE was suspected to be related to study treatment. The endpoint is used to describe the safety experience observed while participants received study drug and were followed. Counts can identify the number of participants recorded with events, but by themselves do not establish that treatment caused those events or how risk would compare under another treatment.
The analysis population is the safety set, defined as all participants who received at least one dose of study drug. The registry record gives group-level counts for serious and other adverse events. It does not provide a complete set of results for every component named in the primary endpoint in the registry record, including severity categories and discontinuations.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record lists serious adverse events for both participant groups. In the ACZ885-treated group, 47 participants were recorded with a serious adverse event among 147 at risk. In the ACZ885 treatment-naïve group, 40 participants were recorded with a serious adverse event among 123 at risk. The record also lists other adverse events for 124 participants among 147 at risk in the ACZ885-treated group and 91 participants among 123 at risk in the treatment-naïve group. These are descriptive counts, not randomized comparisons.
The listed serious-event terms include juvenile idiopathic arthritis (10.6%), histiocytosis haematophagic (6.8%), pyrexia (3.4%), gastroenteritis (2.7%), lymphadenitis (2.4%), and lymphadenopathy (2.4%). The registry record does not explain the denominator or coding details for these term percentages in the registry record for this analysis, so they should be read as reported rather than reinterpreted as group-specific rates.
These counts are not directly comparable as evidence of a difference between the groups. Participants entered the study with different treatment histories, were not randomly allocated, and had different stated follow-up limits: Week 271 for ACZ885-treated participants and Week 145 for treatment-naïve participants. The record does not report exposure-adjusted rates or a statistical comparison accounting for follow-up. Differences in counts could reflect differences in group composition, observation time, or other factors, and the record does not establish which explanation applies.
The primary endpoint includes several safety categories, but the registry entries available for this analysis give only the group counts for serious and other adverse events, plus selected serious-event terms. The record does not report deaths in the listed group data. It also does not provide complete counts for all listed endpoint categories, such as events by severity, treatment-related events, or events leading to discontinuation.
The study’s secondary outcomes include measures of response, steroid use, remission, and health status. Their inclusion describes what the study was designed to assess, but does not establish that results for those outcomes are present in this record. The registry record does not report their results in the registry record for this analysis. Accordingly, the reported safety counts should be interpreted as a limited description of observed events, not as proof of efficacy, causation, or comparative safety.
9. Statistical Methods Explained
What does a participant count describe? A participant count states how many people in a defined analysis group were recorded with an event. For this study, the primary safety population is the safety set: all participants who received at least one dose of study drug. The reported serious-event counts are 47 among 147 in the ACZ885-treated group and 40 among 123 in the treatment-naïve group. The other adverse-event counts are 124 among 147 and 91 among 123, respectively. These are reported counts; no additional rates or contrasts are needed to describe them.
Why is this not a treatment-effect comparison? A randomized comparison uses allocation designed to make treatment groups comparable, subject to chance variation. This study’s allocation is listed as not applicable, its model as single-group, and its masking as none. The two reported groups reflect prior treatment status, not random assignment to canakinumab versus a control. General statistical interpretation therefore treats the group counts as descriptive. They cannot isolate a causal effect of treatment from differences in participants, their treatment history, or the time they were observed.
Why does follow-up time matter? A count accumulates over the observation period. If one group can be observed for longer, it has more opportunity to have an event recorded. Here, the stated endpoint timeframe extends through Week 271 for ACZ885-treated participants and through Week 145 for treatment-naïve participants. The record does not report exposure-adjusted rates or individual follow-up time, so the counts should not be read as though observation time were identical. General methods for comparing event occurrence over unequal follow-up can use person-time or time-to-event methods, but the registry record does not report such analyses for these results.
What does an event percentage mean? The registry lists percentages for selected serious-event terms: juvenile idiopathic arthritis (10.6%), histiocytosis haematophagic (6.8%), pyrexia (3.4%), gastroenteritis (2.7%), lymphadenitis (2.4%), and lymphadenopathy (2.4%). A percentage is a proportion relative to a denominator, but the denominator and calculation details for these listed terms are not reported in the registry record. No denominator should be inferred from the participant-group counts. These percentages also describe event terms, not a randomized comparison of treatment groups.
What can a confidence interval add? General explanation: a confidence interval describes the uncertainty around an estimated quantity under the assumptions of the method used. It is not a guarantee that the true value lies within the interval, and it does not correct for bias from non-randomized group differences or unequal observation. Confidence intervals for the primary safety counts are not reported in the registry record. Nor is a statistical test comparing these groups reported.
Why can over-dispersion matter? General explanation: when observed counts vary more than a simple model expects, a model that assumes less variability can produce uncertainty estimates that are too narrow. Over-dispersion is relevant to some count-data analyses, but the record does not report a count model or an assessment of over-dispersion. The available results are participant counts, not a reported fitted count model.
What is the role of planning calculations? The record’s sample-size assumptions describe planning illustrations based on an observed effect, not the trial’s original design. They specify a two-sided significance level of 0.05, equal allocation, and a normal approximation, with the effect to detect defined as a stated fraction of the observed effect. Such illustrations answer a hypothetical planning question: how large a future study might need to be under those assumptions. They are not observed power, do not alter the uncertainty of the current results, and should not be presented as the trial’s design justification. The registry record does not report the trial’s sample-size justification or statistical plan.
General statistical practice distinguishes prespecified analyses from exploratory summaries, considers the analysis population, and explains how missing observations are handled. The registry record’s the registry entries identify the safety set for the primary endpoint, but do not report the detailed analysis procedures, confidence intervals, hypothesis tests, or a statistical model. Those omissions limit what can be inferred from the displayed counts.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists 19 outcome measures and zero analyses in the available information. The primary outcome itself includes multiple safety categories: AEs, SAEs, events by severity, events leading to discontinuation, and treatment-related AEs and SAEs. Secondary outcomes cover response thresholds, steroid tapering, dose reduction, clinical remission, disability, well-being, pain, and health-related quality of life. Considering many outcomes can raise multiplicity concerns because repeated testing may increase the chance of at least one apparently notable result. However, a multiplicity adjustment or testing hierarchy is not reported in the registry record, and the record does not provide statistical analyses for these outcomes in the registry record for this analysis.
The primary safety analysis population is defined as all participants who received at least one dose of study drug. The population definitions for the secondary outcomes are not reported in the registry record. The record also does not report how missing outcome data were handled, whether participants with incomplete follow-up were included in each analysis, or whether any imputation method was used.
These missing details affect interpretation. Without information about missingness and analysis populations, it is not possible to assess whether outcome summaries represent all enrolled participants, only those with available measurements, or another subset. Without the statistical plan, it is also not possible to determine which comparisons or outcome definitions were prespecified. The listed outcome measures describe the scope of assessment, but do not substitute for reported analysis methods or results.
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 |
|---|---|---|---|
| ACZ885 Treated | 47 | 147 | 32.0% |
| ACZ885 Treatment Naive | 40 | 123 | 32.5% |
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 |
|---|---|
| ACZ885 Treated | 124 of 147 |
| ACZ885 Treatment Naive | 91 of 123 |
Most frequent serious adverse event terms
| Event term | Organ system | ACZ885 Treated | ACZ885 Treatment Naive |
|---|---|---|---|
| Juvenile idiopathic arthritis | Musculoskeletal and connective tissue disorders | 14 of 147 | 13 of 123 |
| Histiocytosis haematophagic | Blood and lymphatic system disorders | 10 of 147 | 6 of 123 |
| Pyrexia | General disorders | 5 of 147 | 4 of 123 |
| Gastroenteritis | Infections and infestations | 4 of 147 | 2 of 123 |
| Pneumonia | Infections and infestations | 2 of 147 | 3 of 123 |
| Lymphadenopathy | Blood and lymphatic system disorders | 1 of 147 | 3 of 123 |
| Varicella | Infections and infestations | 3 of 147 | 1 of 123 |
| Leukopenia | Blood and lymphatic system disorders | 1 of 147 | 2 of 123 |
| Lymphadenitis | Blood and lymphatic system disorders | 0 of 147 | 3 of 123 |
| Abdominal pain | Gastrointestinal disorders | 2 of 147 | 1 of 123 |
Most frequent non-serious adverse event terms
| Event term | Organ system | ACZ885 Treated | ACZ885 Treatment Naive |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 47 of 147 | 32 of 123 |
| Pyrexia | General disorders | 38 of 147 | 27 of 123 |
| Cough | Respiratory, thoracic and mediastinal disorders | 37 of 147 | 28 of 123 |
| Rhinitis | Infections and infestations | 35 of 147 | 26 of 123 |
| Arthralgia | Musculoskeletal and connective tissue disorders | 36 of 147 | 25 of 123 |
| Upper respiratory tract infection | Infections and infestations | 36 of 147 | 24 of 123 |
| Headache | Nervous system disorders | 30 of 147 | 24 of 123 |
| Vomiting | Gastrointestinal disorders | 35 of 147 | 18 of 123 |
| Oropharyngeal pain | Respiratory, thoracic and mediastinal disorders | 36 of 147 | 17 of 123 |
| Juvenile idiopathic arthritis | Musculoskeletal and connective tissue disorders | 23 of 147 | 27 of 123 |
Serious events with the highest arm-level rate: juvenile idiopathic arthritis (10.6%), histiocytosis haematophagic (6.8%), pyrexia (3.4%), gastroenteritis (2.7%), lymphadenitis (2.4%).
The serious adverse event counts are 47 among 147 participants in the ACZ885-treated group and 40 among 123 in the ACZ885 treatment-naïve group. Other adverse events are listed for 124 among 147 and 91 among 123, respectively. These are participant counts recorded in the safety set, which includes participants who received at least one dose of study drug.
The group labels reflect prior treatment status, not random assignment. The stated follow-up limits also differ: Week 271 for ACZ885-treated participants and Week 145 for treatment-naïve participants. Therefore, the counts do not provide a like-for-like estimate of comparative risk. The record does not report exposure-adjusted rates or a statistical comparison. The listed serious-event terms and percentages are descriptive entries; the denominator for those percentages is not reported in the registry record. Deaths are not reported in the registry record.
“Serious” is a regulatory classification based on outcomes such as life-threatening events, hospitalization, disability, or other clinically significant consequences; it does not mean that every event was judged related to treatment. The registry record defines treatment-related events separately, based on the investigator’s suspicion of a relationship, and does not report complete group counts for that category in the registry record for this analysis.
12. What the Result Does, and Does Not, Mean
The results describe adverse events recorded in an open-label extension study of canakinumab for participants with SJIA. They show that the registry recorded serious and other adverse events in both the previously treated and treatment-naïve groups during the stated follow-up. Selected serious-event terms and their reported percentages are also listed. These descriptions can help readers understand what kinds of events appeared in the record and how many participants were recorded with broad event categories.
They do not establish that canakinumab caused any individual event. The AE definition includes events whether or not related to study drug, while treatment relationship was based on investigator judgment. Nor do these data establish that canakinumab prevents or improves SJIA: the registry entries available for this analysis do not include results for the listed efficacy and health-status outcomes.
The counts do not establish whether safety differed between the two groups. There was no randomized control group, the groups differ by treatment history, and their stated follow-up limits differ. The record does not report an adjusted comparison, exposure-adjusted rates, or uncertainty intervals for these counts. Any apparent numerical contrast should therefore remain descriptive, without attributing it to treatment or to a particular participant characteristic.
The study’s open-label extension design is intended to describe longer-term experience in the populations enrolled, but the registry record does not provide individual follow-up durations or all endpoint components. It also does not report deaths in the listed group data. As a result, the findings should be understood within the scope of the outcomes and details actually reported, not as a complete account of all possible safety or efficacy questions.
13. Why This Trial Matters Statistically
This study is statistically informative as an example of why design and follow-up context matter when interpreting event counts. The record reports two groups defined by prior canakinumab treatment status, but does not describe random allocation to treatment and control. The counts can characterize events recorded in each group, yet they cannot provide the protection against confounding that a randomized comparison is designed to offer.
The different stated follow-up limits are also important. Event counts accumulate while participants are observed, so counts from groups with different observation windows should not automatically be compared as rates. The registry record does not report exposure-adjusted estimates. This makes it especially important to describe the findings as counts and to avoid interpreting a numerical difference as evidence of a treatment effect.
The endpoint illustrates another useful distinction: an adverse event is not necessarily considered treatment-related, while an SAE is classified by seriousness criteria. The registry defines these categories and states that treatment relationship was based on investigator judgment. Keeping the categories separate prevents event occurrence, seriousness, and suspected causation from being treated as interchangeable concepts.
Finally, a list of outcomes is not equivalent to a complete statistical analysis. The record includes safety, response, steroid-use, remission, and quality-of-life outcomes, but detailed analysis methods and results for many measures are not reported in the registry record for this analysis. The record therefore supports a bounded descriptive reading rather than broad claims about comparative effectiveness or safety.
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 study is open-label and does not report a randomized control group. Participants are distinguished by prior treatment status, so comparisons between ACZ885-treated and treatment-naïve groups may reflect differences beyond treatment history. The registry record does not report adjusted comparisons that could address such differences.
The stated endpoint timeframe differs by group, ending at Week 271 for ACZ885-treated participants and Week 145 for treatment-naïve participants. Individual follow-up duration, exposure time, and exposure-adjusted event rates are not reported in the registry record. This limits interpretation of group counts as comparative measures of event occurrence.
The reported safety information is incomplete relative to the full primary endpoint definition. Group counts are available for serious and other adverse events, but complete counts for severity categories, treatment-related events, and discontinuations are not reported in the registry record for this analysis. Deaths are not reported in the registry record. The denominator and calculation details for the listed serious-event term percentages are also not reported.
Detailed statistical methods, confidence intervals, hypothesis tests, the sample-size justification, missing-data procedures, and multiplicity handling are not reported in the registry record. Results for the listed secondary response and health-status outcomes are not reported in the registry record for this analysis. These limitations mean the record supports description of the reported safety counts, but not a full assessment of comparative safety, efficacy, or precision.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: An Open-label Extension Study of Canakinumab in Patients With Systemic Juvenile Idiopathic Arthritis and Active Systemic Manifestations Manifestations and Response Characterization Study in Canakinumab Treatment-naïve Patients With Active SJIA With and Without Fever. — NCT00891046.
- Registry record last updated 2019-03-26; status last verified 2018-07.
- Results first posted 2017-03-10.
- 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
NCT00891046 is a completed phase 3, open-label extension study of canakinumab in participants with systemic juvenile idiopathic arthritis. The registry record lists enrollment of 270, a start date of 2009-09, and primary completion in 2014-12. The study included previously treated participants and canakinumab treatment-naïve participants with active SJIA with or without fever.
The primary endpoint concerns participant counts for adverse events and serious adverse events, including severity, discontinuations, and investigator-assessed treatment relationship. The safety set includes all participants who received at least one dose. Reported group counts include serious adverse events for 47 among 147 ACZ885-treated participants and 40 among 123 treatment-naïve participants. The groups are not a randomized comparison, and their stated follow-up limits differ.
The registry record does not report complete results for all primary and secondary outcomes, detailed statistical methods, missing-data procedures, or multiplicity handling in the registry record for this analysis. The available safety findings are descriptive and do not establish causation or comparative treatment effects.