A Study to Continue ASP015K Treatment to Rheumatoid Arthritis Patients Who Completed Phase IIb Study or Phase III Study of ASP015K: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Continue ASP015K Treatment to Rheumatoid Arthritis Patients Who Completed Phase IIb Study or Phase III Study of ASP015K (NCT01638013), a non-randomized phase 3 study. The primary outcome is Number of Participants With Adverse Events.

2. Clinical Question

This study asked about the safety and efficacy of long-term administration of ASP015K in people with rheumatoid arthritis who had completed a Phase IIb or Phase III study of ASP015K. The registry identifies the study drug as peficitinib and describes the trial as an open-label extension. Its primary outcome was the number of participants with adverse events, assessed from baseline through the end of the study, up to week 376.

The secondary outcomes include ACR20, ACR50 and ACR70 responses using CRP or ESR, and changes in DAS28-CRP or DAS28-ESR from the baseline of the preceding study. These outcomes were specified through week 372. Their inclusion does not by itself establish that results or statistical comparisons were reported.

3. Trial Design

The registry describes a Phase 3, non-randomized, open-label, single-group study. It was designed as an extension for people who had completed a qualifying earlier ASP015K study, rather than as a trial that randomized participants to peficitinib or a concurrent control treatment. Enrollment was recorded as 843, and the study status is completed.

The three groups in the posted adverse-event data are identified by the preceding study participants completed: 015K-CL-RAJ1, 015K-CL-RAJ3 and 015K-CL-RAJ4. These labels describe participant cohorts, not randomized treatment assignments. Although the registry lists different starting-dose descriptions for the cohorts, it is not appropriate to treat these cohort data as a controlled comparison. The available descriptions also indicate that dose adjustment was possible; details beyond the stated descriptions are not reported in the registry record.

The study began on 2012-06-13, and its primary completion date was 2019-09-30. The primary safety outcome covered baseline through the end of the study, up to week 376. Several secondary rheumatoid arthritis response and disease-activity outcomes were specified through week 372. These outcome timeframes describe planned assessment windows; they do not establish that every participant was followed for the full period.

Open-label means the study was not masked, while non-randomized means allocation was not random. In this design, the registry does not provide a randomized contrast that can isolate the effect of treatment from differences in participant history, follow-up, or other factors. The record does not report a separate control group. It also does not report the protocol details needed to reconstruct how eligibility, dose adjustments, or follow-up decisions were handled beyond the descriptions noted above.

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: For participants who were on 50mg at the time of peficitinib approval, dose was increased to 100mg. Participants whose dose increment was not possible were discontinued.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety Population: All participants who received at least 1 dose of the 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: Full analysis set (FAS) : All participants who received at least 1 dose of the study drug and had measurements for any of the efficacy endpoints. Data reported is from baseline of preceding study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Adverse Events, measured over Baseline up to end of study (EOS) (up to week 376).

The primary endpoint is the number of participants with adverse events. An adverse event was defined as an untoward medical occurrence in a participant who received study drug, whether or not it was considered causally related to treatment. The definition includes unfavorable or unintended signs, including abnormal laboratory findings, symptoms, and diseases temporally associated with use of the study drug.

The stated timeframe was baseline through the end of the study, up to week 376. The endpoint population was the safety population, defined as all participants who received at least one dose of study drug. Counting participants with an event is a straightforward way to describe how many people in the safety population had an adverse event recorded during the specified observation period. It does not, by itself, indicate how many separate events each person experienced, how long participants were observed, or whether an event was caused by study treatment.

The registry also reports serious adverse events and other adverse-event counts by preceding-study cohort. Those categories offer safety context, but they should not be conflated with a treatment-versus-control estimate: the cohorts were not randomized comparison arms. The primary endpoint description does not establish a causal attribution rule, and the record does not report an inferential estimate for the primary endpoint. The definition explicitly allows events that are not considered related to treatment.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What kind of outcome is being counted?

The primary endpoint is a participant count: it concerns whether participants had an adverse event during the stated follow-up, rather than measuring a continuous quantity such as a laboratory value. For a binary participant-level outcome, each participant can be classified according to whether the event occurred. Counts are useful for describing the observed safety experience, but a count alone is not a rate unless its denominator and observation time are appropriately specified. The primary outcome definition names the safety population and gives a follow-up window, but the record does not provide a time-adjusted analysis of adverse-event occurrence.

The adverse-event listings distinguish serious adverse events from other adverse events by cohort. The cohort figures include the number at risk and the number with the event for each category. These entries should be read as recorded counts and denominators, not as separately randomized treatment arms. The record does not report an inferential analysis to compare these entries.

What does a confidence interval usually add?

In general, a confidence interval conveys uncertainty around an estimated quantity under the assumptions of a statistical method. A narrow interval typically indicates greater precision than a wide interval, while an interval that includes values compatible with no difference may leave the direction or size of a contrast uncertain. These concepts apply only when an estimate and its interval have actually been calculated and reported. The registry record lists no analyses for this study, so there is no reported inferential interval on which to base that kind of precision assessment.

A p-value, in general, describes how compatible data are with a specified null model under the assumptions of a test. It is not the probability that a treatment works, nor does it measure clinical importance. No p-value or hypothesis test is reported in the registry record. In particular, the cohort counts should not be treated as evidence of a statistically significant difference simply because the counts are not identical.

Why does the design matter for statistical interpretation?

Randomization is one way to make comparison groups similar, on average, with respect to factors that might influence outcomes. This study is explicitly non-randomized and single-group. Its three reported cohorts reflect different preceding studies, not randomly assigned arms. Descriptive comparisons between them may therefore be affected by differences in who entered each cohort, their prior study history, or the amount of observation. Statistical adjustment could address some measured differences in an appropriate analysis, but no such analysis is reported, and adjustment cannot automatically remove unmeasured differences.

Open-label status means the trial was not masked. That can matter to outcome recording and clinical management, particularly for outcomes involving judgment. The adverse-event definition includes a broad range of medical occurrences and does not require a causal relationship to study drug. Consequently, event counts are not equivalent to counts of events judged to be caused by peficitinib.

How should planning calculations be understood?

General sample-size calculations answer a planning question: under stated assumptions, what sample size would be needed to detect a specified effect with a chosen power and significance level? They are not measurements of what happened in a trial. The planning assumptions associated with this record use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is expressed as a fraction of the observed effect. For time-to-event outcomes, the planning convention is a total event count, while other outcomes use participants per arm.

These are planning assumptions, not a description of this extension's design. The study was single-group and non-randomized, so an equal-allocation two-arm illustration should not be confused with actual assignment in this trial. Any sample-size illustration is not observed power, and it cannot show that the study was adequately powered to detect safety or efficacy effects. The registry record does not report a sample-size justification, a prespecified statistical analysis plan, or interim analyses.

What can be concluded from counts without a model?

Counts describe the events recorded among the participants represented by each denominator. A rate comparison would require a clearly defined estimand and appropriate handling of differences in follow-up. A model-based comparison would also require stated assumptions and a method. The record does not report a time-to-event analysis, adjustment for exposure time, or a model comparing cohorts. Therefore, the posted adverse-event figures should remain descriptive. They are informative about what was recorded in this extension, but do not establish comparative safety or causation.

10. Multiplicity, Missing Data and Analysis Populations

The registry lists multiple secondary outcomes: ACR20, ACR50 and ACR70 responses based on CRP and ESR, as well as changes in DAS28-CRP and DAS28-ESR. Several assessment windows extend through week 372. When many outcomes or time points are tested, the chance of at least one apparently unusual result can increase if no multiplicity strategy is used. In general, multiplicity procedures can control that risk or define a hierarchy of questions. The statistical plan and any multiplicity adjustment are not reported in the registry record, and the presence of listed outcomes does not establish that formal tests were conducted.

The registry record lists no inferential analyses. It does not report how missing outcome data were handled, whether participants who discontinued treatment remained under observation, or whether any imputation or sensitivity analyses were used. Those details matter because missingness can affect both the number of observed events and the interpretation of response outcomes. The record also does not report outcome-specific denominators over time for the secondary measures.

The primary outcome population is defined as participants who received at least one dose of study drug. That definition clarifies who is eligible for inclusion in the safety population, but it does not supply a full account of analysis populations for the secondary endpoints. The record does not report a separate intention-to-treat population, per-protocol population, or rules for handling participants with incomplete follow-up. No assumptions about those methods should be inferred from the cohort labels or the study's completed status.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: pneumonia (2.7%), herpes zoster (2.2%), tendon rupture (2.0%), intervertebral disc protrusion (1.5%), calculus urinary (1.3%).

The serious adverse-event figures are recorded by preceding-study cohort. Participants who completed 015K-CL-RAJ1 had 59 serious adverse events among 201 at risk; those who completed 015K-CL-RAJ3 had 56 among 225; and those who completed 015K-CL-RAJ4 had 84 among 417. The other adverse-event figures are 181 among 201, 174 among 225 and 358 among 417, respectively. The registry also records deaths as 0, 1 and 1 in the same cohort order.

These entries are descriptive. The cohorts are not randomized treatment and control groups, and the counts do not account for potentially differing observation time. They should not be read as rates, comparative risk estimates, or proof that an event was caused by study drug. The adverse-event definition includes occurrences regardless of whether a causal relationship was established.

The serious-event terms listed include Pneumonia at 2.7%, Herpes zoster at 2.2%, Tendon rupture at 2.0%, Intervertebral disc protrusion at 1.5%, Calculus urinary at 1.3% and Cellulitis at 1.0%. These listed terms do not replace the full safety assessment, and the registry record does not report a comparative analysis of them.

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

The results are best understood as descriptive safety information from an open-label extension involving people who had completed earlier ASP015K studies. The registry records adverse events by preceding-study cohort, along with cohort denominators, serious-event counts, other adverse-event counts and deaths. It also identifies serious adverse-event terms and their recorded percentages. This information describes events captured during the study; it does not establish why those events occurred.

The study does not provide a randomized control group. As a result, the cohort figures cannot answer a controlled question about whether peficitinib caused more or fewer events than another treatment or no treatment. Comparisons across the preceding-study cohorts also cannot be interpreted as treatment comparisons because cohort membership was based on prior study completion rather than random assignment. The record does not report statistical estimates that adjust for differences in participant characteristics or follow-up.

The primary endpoint concerns participants with adverse events, and the registry defines adverse events broadly, without requiring a causal relationship to study drug. The observed counts therefore include events that may or may not have been considered related to treatment. The posted serious-event terms likewise do not, on their own, establish causation or provide a complete account of all safety outcomes.

The registry identifies ACR response and DAS28 change as secondary outcomes, but their results are not reported in the registry record. Consequently, the available record does not support conclusions about the magnitude or precision of rheumatoid arthritis response. It also does not report confidence intervals, hypothesis tests, or a statistical plan that would clarify how efficacy or safety comparisons were intended to be assessed.

In general, a single-group extension can document events during continued exposure and provide longer-term descriptive follow-up. Its findings have a different role from a randomized comparison: they can characterize what was recorded in the enrolled population, but cannot isolate a treatment effect from other explanations. The appropriate conclusion is limited to the posted design and descriptive adverse-event data, not a claim that treatment is effective, ineffective, safe, or unsafe.

13. Why This Trial Matters Statistically

This study is statistically informative as an example of how an extension study differs from a randomized efficacy comparison. Participants entered after completing earlier studies, and the registry organized adverse-event results by the preceding study. That structure permits cohort-based description, but it does not create exchangeable treatment and control groups. Recognizing this distinction prevents descriptive counts from being mistaken for causal estimates.

The primary endpoint is a participant count over a long stated follow-up window. For safety interpretation, the event definition matters: an adverse event is a medical occurrence temporally associated with study-drug use, whether or not it is considered related. The endpoint therefore captures a broad safety experience rather than a count restricted to events attributed to peficitinib. The separate serious-event listings add detail, while still requiring cautious interpretation of denominators and follow-up.

The registry also makes visible an important reporting boundary. It lists secondary efficacy outcomes, but does not report their results or inferential analyses. Outcome names alone do not tell readers the size, precision, or direction of a treatment effect. Nor can cohort counts substitute for confidence intervals, hypothesis tests, or an analysis plan. Explicitly distinguishing planned outcomes from reported results is essential for evidence synthesis and for preventing unsupported conclusions.

Finally, the study illustrates why long-term descriptive evidence and comparative evidence answer different questions. Extension data can describe events among participants continuing from earlier trials. Without randomization and a reported comparative analysis, however, differences between cohorts remain open to alternative explanations. The record supports a careful account of the study's design and recorded safety data, while leaving comparative efficacy and causal safety questions unresolved.

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 design limitation is that the study was non-randomized, open-label and single-group. The three adverse-event cohorts were defined by the preceding studies participants completed, rather than by randomized assignment to treatment strategies. Comparisons among cohorts therefore cannot be interpreted as controlled estimates of treatment effects. Differences may reflect cohort composition, prior study history, exposure or follow-up, and the registry record does not report analyses that account for these factors.

The primary outcome covers baseline through the end of the study, up to week 376, while listed secondary outcomes extend through week 372. These maximum timeframes do not show how long each participant was observed. The registry record does not report exposure-adjusted event rates or a time-to-event analysis. Counts and denominators alone cannot describe differences in person-time when follow-up may vary.

The adverse-event definition includes occurrences whether or not they were related to study drug. This is appropriate for describing a broad safety population but limits causal interpretation. The serious-event terms and death counts are also descriptive; the record does not report a comparative analysis or additional context that would establish attribution.

Statistical methods, a sample-size justification, interim analyses, missing-data handling and multiplicity procedures are not reported in the registry record. The record lists no inferential analyses, confidence intervals or hypothesis tests. Although ACR and DAS28 outcomes are named, their results are not reported. These limitations prevent assessment of precision and prevent conclusions about comparative efficacy or the statistical strength of differences.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Continue ASP015K Treatment to Rheumatoid Arthritis Patients Who Completed Phase IIb Study or Phase III Study of ASP015K — NCT01638013.
• Registry record last updated 2024-10-28; status last verified 2024-10.
• Results first posted 2020-10-23.
• 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.

18. Record Summary

This is a completed Phase 3, open-label, non-randomized, single-group extension study of peficitinib, also identified as ASP015K, in people with rheumatoid arthritis who completed an earlier qualifying ASP015K study. Enrollment was recorded as 843. The study began on 2012-06-13, and the primary completion date was 2019-09-30.

The primary outcome was the number of participants with adverse events from baseline through the end of the study, up to week 376, in the safety population of participants who received at least one dose. The posted safety data are organized by preceding-study cohort. Secondary outcomes include ACR response measures using CRP or ESR and changes in DAS28-CRP or DAS28-ESR through week 372.

The registry record lists no inferential analyses. Secondary outcome results, missing-data methods, multiplicity methods and a statistical analysis plan are not reported in the registry record. The adverse-event counts are descriptive and do not provide a randomized comparison.