Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213) (NCT04434937), a na phase 2 study. The primary outcome is Objective Response Rate (ORR).

2. Clinical Question

The study’s stated purpose was to assess parsaclisib efficacy and safety in Japanese participants with relapsed or refractory follicular lymphoma. The endpoint addresses whether participants met criteria for a complete or partial response during the specified assessment period. Because there was no control group, the study’s central question is descriptive: what response proportion was observed among the analyzed participants? It cannot, by itself, estimate a treatment difference against a concurrent comparator.

The registry also lists secondary outcomes covering duration of response, progression-free survival, overall survival, target-lesion change, and treatment-emergent adverse events. These outcomes broaden the questions beyond initial response, but their numerical results are not reported in the registry record. The enrollment count and endpoint definitions alone do not establish the magnitude or precision of any efficacy result.

3. Trial Design

CITADEL-213 is a phase 2, multicenter, open-label study of parsaclisib in Japanese participants with relapsed or refractory follicular lymphoma. Its official title identifies parsaclisib as a PI3Kδ inhibitor. The registry lists a single-group model, allocation as not applicable, and no masking. In practical terms, the registry describes one treatment group rather than a randomized comparison, and treatment assignment was not blinded.

The study enrolled 42 participants. The registry records the study as completed, with a start date of 2020-09-30 and a primary completion date of 2023-02-16. The sponsor is Incyte Biosciences Japan GK. These registry entries describe the study record and do not, by themselves, establish when every participant entered or finished follow-up.

Parsaclisib was the listed intervention. The arm description states that participants took it orally once daily with water, without regard to food, except on mornings of pharmacokinetic clinic visits. The safety group is titled Parsaclisib 20 mg/2.5 mg. Further details about dose changes, treatment duration, adherence, or individual exposure are not reported in the registry record.

The primary outcome was objective response rate, assessed by an independent review committee according to revised lymphoma response criteria. Its stated timeframe was up to approximately 3 years. The registry defines the primary analysis population as enrolled participants who received at least one dose. It also lists secondary outcomes for response duration, progression-free survival, overall survival, lesion-size change, and treatment-emergent adverse events.

A single-group, open-label design can describe outcomes observed during treatment and follow-up, but it does not separate treatment effects from changes that might have occurred without treatment or under another treatment. The registry record does not report a protocol-based sample-size justification, a control-group plan, or the rationale for the design.

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: This study was conducted at 19 study centers in Japan.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: all participants enrolled in the study who received at least 1 dose of parsaclisib. Confidence intervals were calculated based on the exact method for binomial distributions.

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.

6. Primary Endpoint

The registry lists the primary outcome as Objective Response Rate (ORR), measured over up to approximately 3 years.

Objective response rate is the percentage of participants with either a complete response or a partial response, as determined by an independent review committee. It combines two categories of tumor response into a binary endpoint: each assessed participant either meets the response definition or does not. The endpoint was to be assessed over a timeframe of up to approximately 3 years.

The registry describes response using revised response criteria for lymphoma. A complete response requires regression of target nodes or nodal masses to at most 1.5 centimeters in longest transverse diameter, no nonmeasured lesions or new lesions, regression of organ enlargement to normal, and normal bone marrow by morphology with negative immunohistochemistry when morphology is indeterminate. A partial response requires at least a 50% decrease in the sum of products of diameters for up to 6 target measurable nodes and extranodal sites, no increase in nonmeasured lesions, spleen regression by more than 50% in length beyond normal, and no new lesions.

Response rate is used because it gives a readily interpretable summary of the proportion meeting prespecified response criteria. Independent review can provide an assessment separate from the treating investigator’s judgment, although the registry does not report reviewer procedures or agreement. The registry record does not list the observed response count, percentage, or confidence interval. The endpoint definition therefore explains what would count as a response, but does not reveal the result.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

How should a response proportion be understood?

Objective response rate is a binary-outcome summary expressed as a percentage of participants. Each participant is classified according to whether the independent review committee’s assessment meets the complete-response or partial-response criteria. The resulting proportion describes the share of the analyzed population who met either criterion. It does not describe how long a response lasted, how much an individual participant’s lesions changed, or whether the treatment caused the response.

In general, a binary percentage is most informative when read alongside its denominator and a measure of uncertainty. The denominator clarifies which participants contributed to the proportion, and an interval communicates how much uncertainty surrounds the estimate. Here, the registry identifies the Full Analysis Set as enrolled participants who received at least one dose, and it says confidence intervals were calculated using the exact method for binomial distributions. However, the response estimate, denominator used in the result, and confidence interval endpoints are not reported in the registry record.

What does an exact binomial confidence interval mean?

General explanation: a binomial model describes outcomes where each observation falls into one of two categories, such as meeting or not meeting a response definition. An exact interval uses the binomial probability model to calculate limits for the underlying response proportion. Unlike a point estimate alone, the interval makes uncertainty visible. It does not mean that the true response proportion has a specified probability of lying within the particular calculated interval; rather, it is a procedure designed to provide coverage over repeated use under its assumptions. Since the registry record does not give the interval limits, its width and the precision of the estimate cannot be evaluated.

The registry’s endpoint is determined by an independent review committee. In general, independent assessment can help distinguish endpoint review from the treating investigator’s assessment. The record does not describe adjudication procedures, reviewer masking, the handling of disagreements, or the number of assessments available for review. Those process details should not be assumed.

What do the design features imply for inference?

The trial is single-group, open-label, and has no randomized allocation. General statistical interpretation: a single-group estimate can describe outcomes in the enrolled population, but it does not supply a concurrent counterfactual. Without a control group, differences attributable to treatment cannot be separated from the natural course of disease, participant selection, other care, or assessment conditions. A single-group response proportion is therefore not equivalent to a comparative treatment effect.

Open-label means that masking was none, as recorded. Independent review of the primary endpoint is a distinct design feature, but does not turn the study into a blinded or randomized trial. It may limit some forms of assessment influence, yet the registry record does not report how the committee operated or whether other decisions were blinded. The interpretation should stay within the design actually recorded.

What can be inferred from the safety counts?

General explanation: adverse-event counts describe the number of participants with events observed during the study’s safety observation period. They depend on the population considered at risk, how events are defined and collected, and how long participants are observed. A count does not, on its own, establish causation or compare risk with another treatment. Here, the record lists 42 participants at risk for serious events and 15 affected; it also lists 42 at risk for other treatment-emergent adverse events and 38 affected. The record lists 4 deaths. It does not provide the causal attribution or exposure-adjusted analysis needed to interpret these counts as treatment-specific risks.

What planning assumptions are described?

The registry record does not report the trial’s own sample-size justification or statistical design rationale. A planning illustration associated with the posted analysis uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect set as a stated fraction of the observed effect. These are assumptions for a hypothetical planning exercise, not a description of this single-group study’s actual allocation. The record does not provide numerical planning outputs in the registry record for this analysis.

General explanation: a sample-size calculation asks how many participants may be needed under selected assumptions to detect a specified effect with a chosen operating characteristic. Its result depends on the assumed effect, variability or event rate, allocation, and statistical method. A planning illustration based on an observed effect is retrospective and should not be interpreted as observed power or as evidence that the trial had a particular probability of finding a result. No sample-size justification, interim analysis plan, or detailed statistical analysis plan is reported in the registry record.

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("Parsaclisib 20 mg/2.5 mg")
n      <- c(42)
events <- c(37)
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  Parsaclisib 20 mg/2.5 mg  42  37  88.1  74.4  96.0  75.0  94.8  74.9  94.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint of objective response rate and several secondary outcomes: complete response rate, duration of response, progression-free survival, overall survival, target-lesion change, and treatment-emergent adverse-event measures. When a study examines multiple outcomes, the chance of at least one apparently notable finding can increase if each is interpreted without accounting for the family of tests. General statistical practice may address this through prespecified hierarchies or multiplicity adjustments, but neither approach is described in the registry record.

The record lists no analysis entries. It therefore does not provide numerical endpoint results, p-values, confidence interval limits, or a detailed account of which analyses were performed. The record does specify an exact binomial method for confidence intervals for the primary proportion, but does not state how missing primary endpoint assessments were handled or whether any sensitivity analyses were planned.

The stated Full Analysis Set includes all enrolled participants who received at least one dose of parsaclisib. That definition establishes a treatment-exposed analysis population, but does not explain how participants without an evaluable response assessment would contribute to the response calculation. The number of such participants, if any, and the handling of missing response data are not reported in the registry record.

The registry also does not report whether the analysis population for each secondary outcome differed from the primary population, how censoring was handled for time-to-event outcomes, or whether missing safety information occurred. These omissions limit assessment of analysis choices and the potential for bias. The endpoint names and population definition alone cannot resolve those questions.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: stomatitis (7.1%), covid-19 (4.8%), cardiac failure (4.8%), cytomegalovirus colitis (4.8%), aortic aneurysm (2.4%).

The registry lists 42 participants at risk for serious adverse events and 15 participants with a serious adverse event. For other treatment-emergent adverse events, it lists 42 at risk and 38 affected. The record also lists 4 deaths. The same values appear for the parsaclisib 20 mg/2.5 mg group and the total group, so they should not be added together as separate sets of participants.

The serious adverse event terms listed with percentages are stomatitis, 7.1%; COVID-19, 4.8%; cardiac failure, 4.8%; cytomegalovirus colitis, 4.8%; aortic aneurysm, 2.4%; and arthritis, 2.4%. These are registry-reported percentages attached to the listed terms. The record does not state whether participants could contribute more than one event term, nor does it report event duration or outcome for each term.

These counts are descriptive, not proof of causation. The registry record does not indicate from these figures whether the events or deaths were judged related to parsaclisib, and there is no comparator group for a relative safety assessment. The exposure period and detailed event-collection procedures are not reported in the registry record. The counts therefore characterize recorded events in this study, but do not by themselves quantify comparative risk.

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

The record establishes that CITADEL-213 was a phase 2, open-label, single-group study of parsaclisib in Japanese participants with relapsed or refractory follicular lymphoma. It enrolled 42 participants and named objective response rate as the primary endpoint. The endpoint was based on complete or partial response determinations by an independent review committee using revised lymphoma criteria. Safety information includes counts for serious and other treatment-emergent adverse events and deaths.

Those details do not establish the size of the observed response proportion. The primary outcome value and its 95% confidence interval are not reported in the registry record. Neither can be reconstructed from the enrollment number or endpoint definition. The record also does not give numerical results for the listed secondary efficacy outcomes. Accordingly, no conclusion about the magnitude or precision of response, response duration, survival, or lesion change can be drawn from these registry entries alone.

Even if a response estimate were available, the single-group design would support a description of outcomes among participants in the study, not a randomized comparison with another treatment. It would not show what would have occurred in the absence of parsaclisib or under a different treatment. Open-label conduct and the lack of a concurrent control are relevant when interpreting any observed outcome.

The safety counts indicate that serious and other treatment-emergent adverse events were recorded among participants, and that deaths were listed. They do not establish that parsaclisib caused any particular event or death. The registry record does not report attribution for these figures, and comparative safety cannot be estimated without a comparison group.

The study can therefore be understood as a registry-described, single-group assessment with a defined response endpoint and a set of listed safety outcomes. The posted information does not contain the efficacy results needed to judge the observed response or its uncertainty. It also does not provide the missing-data, multiplicity, or analysis details that would be needed to assess the full statistical conduct of the study.

14. Why This Trial Matters Statistically

This study is statistically notable for the gap between a clearly defined primary endpoint and the absence of its numerical result in the registry record. The response definition is detailed, the independent review committee is identified, and the confidence-interval approach is named. Yet without the response estimate and interval limits, readers cannot evaluate either the outcome’s magnitude or its precision. Endpoint definitions are essential for interpreting results, but they are not substitutes for results.

The design also makes the distinction between descriptive and comparative evidence important. CITADEL-213 is recorded as a single-group, open-label study, with allocation not applicable and no masking. Its outcomes can describe the enrolled participants under study conditions. They cannot, without a comparator, quantify a treatment difference or distinguish a treatment effect from other influences on observed outcomes.

The safety counts illustrate a related interpretive point. Counts and listed percentages can identify events recorded in the study, but their meaning depends on definitions, observation, attribution, and a comparison framework. The registry record lists serious adverse events, other treatment-emergent adverse events, and deaths, but does not establish causality from those figures.

Finally, the record identifies multiple secondary outcomes while listing no analyses. This limits statistical appraisal beyond the endpoint descriptions. Information about missing data, multiplicity, sample-size justification, and analysis procedures is not reported in the registry record. For biostatistical interpretation, the trial is therefore a useful example of why design, endpoint definitions, outcome estimates, uncertainty, and analysis details each contribute distinct information. The presence of one does not fill in the absence of another.

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 primary limitation for interpreting efficacy is that the registry record does not report the primary objective response rate, its response count, or its 95% confidence interval. It also does not report numerical results for the listed secondary outcomes. The endpoint definition and enrolled population cannot be used to infer any of those results.

The single-group, open-label design has no randomized comparator. It can describe outcomes observed in the study, but it does not support a direct estimate of a treatment contrast. The record does not report masking, and its stated masking is none; independent committee review of the primary outcome does not make the overall study blinded.

The stated primary analysis population is participants enrolled who received at least one dose. The registry record does not report the number with evaluable primary endpoint data, the handling of missing assessments, or sensitivity analyses. It also does not provide a detailed statistical analysis plan, interim analysis information, or the study’s sample-size justification. Multiplicity handling for the several listed secondary outcomes is not reported.

For safety, the record lists event counts and selected serious-event terms but does not provide attribution, duration, exposure-adjusted rates, or a comparison group. The listed counts therefore cannot establish causal relationships or comparative risk. Further information about follow-up, event collection, participant disposition, and analysis procedures is not reported in the registry record.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-Label Study of Parsaclisib, in Japanese Participants With Relapsed or Refractory Follicular Lymphoma (CITADEL-213) — NCT04434937.
• Registry record last updated 2024-10-23; status last verified 2024-08.
• Results first posted 2024-01-03.
• 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

CITADEL-213 is a completed phase 2, multicenter, open-label, single-group study of parsaclisib in Japanese participants with relapsed or refractory follicular lymphoma. The registry records 42 enrolled participants, with a study start date of 2020-09-30 and primary completion date of 2023-02-16. The sponsor is Incyte Biosciences Japan GK.

The primary endpoint was objective response rate, assessed by an independent review committee using revised lymphoma response criteria, over up to approximately 3 years. The primary analysis population is described as enrolled participants who received at least one dose; exact binomial confidence intervals were specified. The primary estimate and confidence interval are not reported in the registry record.

Safety information lists 15 participants with serious adverse events, 38 with other treatment-emergent adverse events, and 4 deaths among 42 at risk in each category. The registry record does not establish causation for these events. Numerical results for the secondary outcomes and further analysis details are not reported.