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 Open-Label Extension of the Dose Finding Study (DSC/08/2357/36) in Patients With Poly Juvenile Idiopathic Arthritis (NCT01557452), a na na study. The primary outcome is Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AE) of Interest.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01557452 |
| Phase | NA |
| Condition | Juvenile Idiopathic Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 1 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Italfarmaco |
| Results posted | Yes |
2. Clinical Question
Population
Patients with polyarticular course juvenile idiopathic arthritis who had participated in study DSC/08/2357/36 and had shown clinical benefit of at least pediACR30 response. The registry describes this as an extension for those participants, but does not report further eligibility details or the characteristics of the treated population.
Intervention
Givinostat, described as 0.75 mg/kg BID. The registry states that the patient received this dose from December 28th, 2011 to January 27th, 2014.
Comparator
There was no concurrent comparator arm. The study is listed as a single-group, open-label extension, with allocation and masking recorded as NA and NONE, respectively. Results therefore do not estimate a contrast between givinostat and another treatment or control.
Primary question
The stated primary objective was long-term safety of givinostat among participants who entered the extension after clinical benefit in the prior study. The primary outcome counts participants with serious adverse events and adverse events of interest through the end of treatment, up to 108 weeks. The record describes one adverse event, considered not drug related by the investigator, and no serious adverse events in the posted counts.
This is a safety-focused extension rather than a controlled efficacy trial. The registry also names maintenance of PedACR30 response and reaching PedACR70 response as secondary outcomes. It does not report results for those outcomes in the record described. The clinical question is therefore narrower than whether givinostat is more effective or safer than an alternative: the posted primary data describe adverse-event counts during treatment in this selected extension group.
3. Trial Design
This registry entry describes an open-label extension of the dose-finding study DSC/08/2357/36 in patients with polyarticular course juvenile idiopathic arthritis. The intervention is givinostat, and the study model is single group. Masking is recorded as NONE; allocation is recorded as NA. There is no concurrent comparison group, so the design cannot support a direct treatment-versus-control estimate.
The stated purpose was to examine long-term safety among patients who participated in the earlier study and had a clinical benefit of at least pediACR30 response. The arm description says the patient received 0.75 mg/kg BID from December 28th, 2011 to January 27th, 2014. The primary outcome timeframe is through the end of treatment, up to 108 weeks. These details describe the intended extension and its treatment period; the registry does not report individual treatment duration or additional follow-up procedures.
The record lists a phase of NA, enrollment of 1, and status TERMINATED. It does not report why the study was terminated, whether the recorded enrollment reflects all who entered treatment, or what led to the termination. These details should not be inferred from the status label alone.
The registry lists 3 outcome measures and 0 analyses. The primary outcome concerns participants with serious adverse events and adverse events of interest. The listed secondary outcomes concern maintenance of PedACR30 response and reaching PedACR70 response. Their definitions, analysis populations, and results are not reported in the registry record. With the single-group design and limited posted results, the record supports a descriptive account of reported events, not a controlled comparison or a broad estimate of treatment effects.
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 | Givinostat |
|---|---|
| STARTED | 1 |
| COMPLETED | 1 |
| NOT COMPLETED | 0 |
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 | Givinostat |
|---|---|---|
| Participants analysed | 1 | |
| Age, Categorical: <=18 years | Participants | 1 |
| Age, Categorical: Between 18 and 65 years | Participants | 0 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 1 |
| Sex: Female, Male: Male | Participants | 0 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 1 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Region of Enrollment: Czechia | participants | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AE) of Interest, measured over Through end of treatment, up to 108 weeks..
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | participants |
| Endpoint classification | Binary Endpoint |
The primary endpoint is titled “Number of Participants With Serious Adverse Events (SAE) and Adverse Events (AE) of Interest.” It is a participant count, rather than a continuous measurement or a time-to-event estimate. The timeframe is through the end of treatment, up to 108 weeks. In the description, the registry reports one adverse event during the study period and says the investigator considered it not drug related. The posted adverse-event counts record 0 participants with serious adverse events among 1 at risk and 1 participant with another adverse event among 1 at risk.
Safety endpoints are used to describe unwanted events that occur during treatment and to distinguish serious events from other events of interest. A participant count is easy to interpret as a descriptive summary, but it does not by itself convey the clinical detail, duration, recurrence, or timing of every event. Those details are not reported beyond the description of a mild flu at week 107 of study treatment, no action taken, and spontaneous recovery.
The endpoint is not a measure of comparative risk because there is no concurrent control group. The registry also does not report a formal statistical analysis, an uncertainty interval, or a prespecified definition of adverse events of interest. The count should therefore be read as the safety experience recorded for this extension, not as an estimate of the difference that would occur under another treatment.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The posted safety results are descriptive. The registry reports 0 participants with serious adverse events among 1 at risk, 1 participant with another adverse event among 1 at risk, and 0 deaths. Its narrative identifies the event as a mild flu at week 107 of study treatment, considered not drug related by the investigator. It also states that no action was taken and that the patient recovered spontaneously. These statements describe what the registry records; they do not establish whether treatment caused or prevented an event.
The study is a single-group extension with enrollment of 1 and no concurrent comparator. Consequently, there is no within-trial contrast for estimating how event counts might differ under another treatment or under no treatment. Investigator attribution is part of the event narrative, but attribution is not a randomized causal comparison. The record does not report an inferential analysis or uncertainty interval for the safety counts.
The absence of a recorded serious adverse event in this small extension is not evidence that serious events cannot occur. A count based on a very limited number of participants has little capacity to characterize uncommon events or the range of possible safety experiences. General statistical principle: estimates from small samples are imprecise, and a count of zero can coexist with substantial uncertainty about the underlying event risk. No risk estimate or confidence interval is reported for this endpoint.
The primary objective was long-term safety, but the record does not explain why the trial was terminated or whether its enrollment and follow-up met the original intentions. The listed outcome timeframe extends through treatment, up to 108 weeks, while the arm description gives the treatment period from December 28th, 2011 to January 27th, 2014. These are registry descriptions and should not be treated as a complete account of every participant’s exposure or follow-up.
The secondary outcomes concern PedACR30 maintenance and reaching PedACR70 response. Their results are not reported in the registry record. Therefore, no conclusion about those outcomes can be drawn from the posted results. Overall, the primary endpoint supplies a sparse event-count description for this extension, rather than a comparative or precise estimate of long-term safety.
9. Statistical Methods Explained
The registry identifies a participant-count endpoint and records 0 analyses. It does not report a statistical analysis plan, a model used for the primary outcome, a hypothesis test, an adjustment strategy, or an uncertainty interval. The safest reading is therefore descriptive: the record gives counts of participants with and without reported event categories, without a reported model-based estimate.
What does a participant count tell the reader?
A participant count indicates how many people in the recorded group had an event meeting the endpoint definition. The posted data distinguish serious adverse events from other adverse events and include deaths. Counts are useful for seeing the observed safety experience, but they do not automatically represent a stable estimate of the event frequency in a wider population. Interpretation depends on how many participants were observed, how long they were followed, which events were included, and whether the event definitions were applied consistently. The registry reports enrollment of 1 and the adverse-event risk counts, but does not report detailed event-collection procedures or a formal endpoint definition for events of interest.
Why is there no treatment-effect estimate?
A comparative treatment effect requires a contrast between groups or between treatment conditions. This study is listed as single group and has no concurrent comparator. Its event count therefore describes the extension group rather than a difference between treatment strategies. General statistical principle: a control group can help distinguish events occurring during treatment from events that might also occur because of the underlying condition, background risks, or other influences. Without that contrast, a causal effect cannot be isolated from the posted count. The investigator’s view that the mild flu was not drug related is a reported attribution, not a statistical comparison.
How should uncertainty be understood?
A confidence interval is a range of values that expresses the uncertainty associated with an estimate under a specified statistical method. It is not reported for the primary outcome. General statistical principle: with a very small observed group, an event count—especially a zero count—can be compatible with a wide range of underlying risks. An interval would make that uncertainty more visible, but would still depend on assumptions about the population and event process. No interval should be inferred from the registry counts alone.
For binary outcomes, general methods may estimate an event probability using a binomial model, with an exact or approximate interval. Such methods describe uncertainty under model assumptions; they do not correct the lack of a comparator, missing outcome information, or limited representation of the target population. The registry does not say that a binomial model or any other method was used. It also does not report a calculated event probability or any test result.
What about repeated or correlated events?
The primary endpoint is expressed as participants with events, not as a count of all event episodes. Repeated events in the same participant can matter for safety assessment, but participant-level counts do not reveal whether an event recurred. The record describes one adverse event and does not report a recurrent-event analysis. General statistical principle: when multiple events from the same person are analyzed as separate observations, those observations may be correlated; methods that account for this dependence can be needed. That issue cannot be assessed from the posted participant count.
Over-dispersion is a general concern when observed event variability exceeds what a simple model assumes. It can arise in settings where participants have different underlying event risks or where events cluster. It is not possible to assess over-dispersion from the information reported for this extension, and the registry does not identify a count model or repeated-event model.
Are planning calculations the trial’s analysis?
The sample-size assumptions describe a planning illustration based on an observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. Those are stated planning conventions, not evidence that the extension used a two-arm design or that it had observed power. The actual study is listed as single group, with allocation recorded as NA. A planning illustration cannot substitute for a prespecified trial design or a reported analysis. No sample-size justification or statistical plan is reported in the registry record.
Because no analysis is posted, there is no basis for interpreting statistical significance, adjusted estimates, subgroup findings, or model diagnostics. The meaningful statistical reading is limited to the reported counts and narrative, alongside the uncertainty created by the design and the sparse information.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 3 outcome measures: the primary safety endpoint and secondary outcomes for maintaining PedACR30 response and reaching PedACR70 response. It records 0 analyses. Results for the secondary outcomes are not reported in the registry record, and no inferential tests are posted for the primary outcome.
Multiplicity arises when several outcomes or statistical tests are considered. General statistical principle: examining multiple outcomes can increase the chance that at least one appears notable by chance, so a prespecified testing hierarchy or adjustment may be used when formal inference is intended. The registry does not report a multiplicity strategy, a testing hierarchy, or which outcomes would be included in any formal testing. Since no analyses are listed, there are no reported p-values to interpret or adjust.
The registry does not report how missing endpoint observations were handled, whether any participant discontinued before endpoint assessment, or the completeness of safety follow-up. It also does not identify an analysis population, such as a treated or intention-to-treat population. These details are not reported in the registry record, so the posted event counts cannot be assessed for possible effects of missing data or population-selection rules.
General statistical principle: missing outcomes can bias an estimate when the chance that data are missing is related to the outcome or to participant characteristics. The direction and size of such bias cannot be determined without information about missingness and the planned handling strategy. For this extension, the record gives a limited count and narrative but does not describe those analytic details. No assumption about complete follow-up or missing-data handling should be made from the absence of a reported analysis.
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 |
|---|---|---|---|
| Givinostat | 0 | 1 | 0.0% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Givinostat | 0 of 1 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Givinostat | 1 of 1 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Givinostat |
|---|---|---|
| Influenza | Infections and infestations | 1 of 1 |
The registry reports 0 participants with serious adverse events among 1 at risk, 1 participant with another adverse event among 1 at risk, and 0 deaths. Its narrative says that one adverse event occurred during the study period: mild flu at week 107 of study treatment. The investigator considered it not drug related; no action was taken, and the patient recovered spontaneously.
These are counts recorded for the extension, not a comparison of risk between treatments. The seriousness category and the other-adverse-event category are reported separately. A count of 0 serious adverse events does not show that the risk is zero in a broader population; it means no serious event is recorded in the listed at-risk group. Likewise, the record does not provide an uncertainty interval or a formal estimate of event risk.
The narrative gives limited detail about the reported event. The registry does not report additional event-level information, a complete listing of adverse events of interest, or an analysis of event timing beyond the stated week. The safety figures are therefore best read as a sparse description of observed events, with important uncertainty about how well they characterize safety beyond this extension.
12. What the Result Does, and Does Not, Mean
The result describes the safety experience recorded for an open-label, single-group extension of givinostat in patients with polyarticular course juvenile idiopathic arthritis. The primary endpoint is a count of participants with serious adverse events and adverse events of interest through the end of treatment, up to 108 weeks. The registry reports no serious adverse events, one other adverse event, and no deaths in the posted counts. It identifies the other event as mild flu at week 107 of study treatment and records the investigator’s view that it was not drug related.
This does not establish that givinostat caused the event or that it did not cause the event. Nor does the absence of recorded serious adverse events establish that serious events are impossible or that the treatment is safe in other groups. The available information comes from enrollment of 1, without a concurrent comparator, and the registry reports no statistical analyses or uncertainty interval. Both the single-group design and the limited amount of information constrain conclusions.
The extension enrolled patients who had participated in an earlier study and had clinical benefit of at least pediACR30 response. This selected group is not described in enough detail to assess how representative it is of other patients with the condition. The design also does not permit a direct comparison with patients who did not receive givinostat. The registry’s secondary outcomes address PedACR30 maintenance and reaching PedACR70 response, but their results are not reported.
Accordingly, the record supports only a narrow statement about the event counts and narrative it contains. It does not provide a comparative estimate of safety, establish efficacy, or resolve uncertainty about longer-term outcomes. A broader interpretation would require information not reported in the registry record, including fuller participant and follow-up details, outcome results, and an analysis plan.
13. Why This Trial Matters Statistically
This trial illustrates the distinction between an observed safety count and a treatment-effect estimate. The registry records a small, single-group extension and reports event counts without a comparator or posted statistical analyses. Those details matter because descriptive data can document what occurred in the observed group, while a comparative design is needed to estimate how outcomes differ across treatment strategies.
The record also shows why endpoint labels and denominators matter. Serious adverse events and other adverse events are distinct categories in the posted results, and their at-risk counts are specified. The narrative adds context about the event, including the investigator’s attribution and recovery description. Reading the count together with that narrative is more informative than treating a number alone as a causal conclusion, while still leaving questions unanswered about event definitions and completeness.
The extension’s enrollment of patients with prior clinical benefit further defines the population to which the recorded experience applies. Such selection is relevant when considering whether the findings describe patients outside the extension. The registry does not report enough participant characteristics to assess that question.
Finally, the listing of outcome measures without posted analyses highlights an important reporting limitation. Secondary efficacy-related outcomes are named, but their results are absent; the primary safety objective has a brief event description but no inferential analysis. Statistical interpretation depends not only on outcomes and counts, but also on clear methods, complete reporting, and a design suited to the question. This record offers a bounded description, not a definitive estimate of comparative safety or efficacy.
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 central limitation is the single-group design. With no concurrent comparator, the registry cannot show how the reported event experience differs from an alternative treatment or from an untreated course. The open-label design and lack of masking are recorded, but the registry does not describe procedures for event assessment or whether independent review was used.
The amount of posted safety information is limited. Enrollment is 1, with 0 serious adverse events and 1 other adverse event in the at-risk counts. A count from such a small group cannot characterize uncommon events or provide a precise estimate of event risk. No confidence interval or formal statistical analysis is reported. The record’s attribution of the mild flu as not drug related is the investigator’s assessment and should not be mistaken for a controlled causal finding.
Several details needed to judge completeness are not reported in the registry record: the reason for termination, participant flow, individual follow-up, handling of missing data, the analysis population, and a detailed statistical plan. Although the endpoint timeframe is through treatment, up to 108 weeks, the record does not provide a full account of exposure and observation for each participant. The listed secondary outcomes have no reported results, and adverse-event definitions and collection procedures are not described in detail.
The entry concerns patients who had participated in an earlier study and had shown clinical benefit of at least pediACR30 response. The registry does not provide enough information about their characteristics to determine how broadly the observed experience applies. These limitations constrain the interpretation of both safety and the unreported response outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Open-Label Extension of the Dose Finding Study (DSC/08/2357/36) in Patients With Poly Juvenile Idiopathic Arthritis — NCT01557452.
- Registry record last updated 2021-04-06; status last verified 2021-03.
- Results first posted 2021-04-06.
- 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
The registry record describes NCT01557452, an open-label, single-group extension of the dose-finding study DSC/08/2357/36 in patients with polyarticular course juvenile idiopathic arthritis. It lists givinostat at 0.75 mg/kg BID, enrollment of 1, and status TERMINATED. The treatment period in the arm description is December 28th, 2011 to January 27th, 2014.
The primary objective was long-term safety. The primary endpoint counts participants with serious adverse events and adverse events of interest through the end of treatment, up to 108 weeks. The posted counts report 0 serious adverse events, 1 other adverse event, and 0 deaths. The narrative describes mild flu at week 107 of study treatment, considered not drug related by the investigator; no action was taken, and the patient recovered spontaneously.
The registry lists PedACR30 maintenance and reaching PedACR70 response as secondary outcomes, but does not report their results. It records 0 analyses. No comparator, inferential analysis, uncertainty interval, or detailed missing-data approach is reported in the registry record.