Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation (NCT05282459), a na phase 1, phase 2 study. The primary outcome is Clinical Response: Hematological Improvement - Erythroid (HI-E).

2. Clinical Question

The study’s stated purpose is to assess whether enasidenib is safe and can improve anemia and reduce transfusion needs in people with the specified blood disorders and IDH2 status. It also identifies platelet production and the mechanism of action in endogenous erythropoiesis as objectives. Those objectives describe what the investigators intended to examine; they do not establish that a benefit occurred.

The primary endpoint is a participant count, not a direct comparison between treatments. The registry describes response criteria for participants grouped by transfusion burden, including criteria based on hemoglobin measurements and red blood cell transfusions. The exact primary outcome count is not reported in the registry record, so the stated question cannot be answered from the posted efficacy information.

3. Trial Design

NCT05282459 is registered as a phase Ib/II study. Its official title describes a single-center, open-label study, and the brief description identifies it as single arm. The registry labels the model sequential and lists allocation as NA and masking as none. These details indicate that the record does not describe a randomized, blinded comparison with a separate control group.

The registered intervention is enasidenib mesylate. Participants are described as self-administering it orally every day. The adverse-event record includes groups titled Enasidenib Mesylat 100mg and Enasidenib Mesylat 200mg. Although the model is labeled sequential, the registry record does not report the sequence of dose assignment, dose-escalation rules, or how participants entered those groups.

Enrollment is listed as 17. The registry status is completed, with a start date of 2022-01-12 and a primary completion date of 2024-12-03. Those registry fields describe the study’s recorded status and timing; they do not establish when individual participants were enrolled or followed.

The primary outcome is clinical response measured as hematological improvement—erythroid (HI-E), with a timeframe of 16 weeks. The listed secondary outcomes cover related adverse events, time to and duration of HI-E, platelet and neutrophil hematological improvement, and red blood cell transfusion independence. The record lists seven outcome measures and no posted analyses. It does not report the statistical analysis plan, sample-size justification for the trial, interim analyses, or the analysis populations.

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

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 Clinical Response: Hematological Improvement - Erythroid (HI-E), measured over 16 weeks.

The primary endpoint counts participants who achieve hematological improvement—erythroid (HI-E). It focuses on the erythroid lineage, which is relevant to the study’s stated interest in anemia and red blood cell transfusion needs. A count of responders is an interpretable way to describe how many participants meet a prespecified clinical response definition, but the count alone does not show how precisely the response frequency has been estimated or how it compares with another treatment.

The registry says participants were characterized as nontransfused (NTD), low-transfusion burden (LTB), or high-transfusion burden (HTB), with response defined using criteria for those categories. For NTD, the description specifies at least 2 consecutive hemoglobin measurements at least 1.5 g/dL for a minimum of 8 weeks, during an observation period of 16 to 24 weeks, compared with the lowest mean of 2 hemoglobin measurements. For LTB, the registry states 0 units of red blood cell transfusions. For HTB, it states at least 4 units or at least a 50% reduction in red blood cell transfusions.

The primary outcome timeframe is recorded as 16 weeks, while the NTD criterion refers to an observation period of 16 to 24 weeks. The record does not explain how those time descriptions are reconciled. It also does not report the number meeting HI-E, the number assessed, or outcome results by transfusion-burden category.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The statistical interpretation begins with the type of endpoint. HI-E is recorded as a number of participants, so it is a binary outcome at the individual level: each assessed participant either meets the response definition or does not. The endpoint is then expressed as a count. To interpret a count as a response frequency, its denominator and the handling of participants without an assessment must also be known. The registry record does not report the primary response count, denominator, or missing-outcome handling.

What does a confidence interval describe?

In general, a confidence interval represents uncertainty around an estimate. For a binary response outcome, the estimate is commonly a response proportion, and an interval indicates how compatible a range of underlying response frequencies is with the observed data under the method used. A narrow interval indicates greater precision than a wide interval, all else equal. An interval does not remove design limitations, and it does not turn a single-arm result into a comparison with an untreated or alternative-treatment group. No confidence interval for HI-E is reported in the registry record.

What can a single-arm design estimate?

In general, a single-arm study can describe outcomes observed among its participants. It cannot, by itself, establish what would have happened to the same participants under a different treatment or no treatment. A control group can help provide a contemporaneous reference, especially when outcomes can change over time or can be influenced by other care. Here, the record describes a single-arm, open-label study, with allocation listed as NA and masking as none. It does not report a randomized control comparison. The primary outcome count is also not posted, so even a descriptive response estimate is unavailable.

The registry labels the study model sequential and lists dose groups titled 100mg and 200mg. In general, dose escalation studies may examine safety as dose levels change, but the label alone does not specify the actual escalation procedure. The rules for assignment, the timing of dose changes, and any criteria used to make escalation decisions are not reported in the registry record. No inference about those procedures should be drawn from the group titles alone.

How should the planning illustrations be read?

The record’s sample-size assumptions describe planning illustrations, not the trial’s own design justification. They specify a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is described as a stated fraction of the observed effect. For time-to-event calculations, the assumptions refer to total events using the Schoenfeld method; other calculations are stated in participants per arm. These assumptions are not evidence that the trial had two randomized arms: the study itself is described as single arm. The registry record does not report the trial’s sample-size justification or planning calculation results. The planning illustrations should not be treated as observed power, as a result, or as proof that the study could detect a particular effect.

In general, a planning calculation estimates the sample size needed to detect a specified effect under stated assumptions. Its output depends on the assumed effect, significance level, allocation, analysis method, and other design choices. A calculation based on an observed effect is especially dependent on the estimate used as its starting point. If the underlying observed effect is unavailable, the planning illustration cannot be independently interpreted from the registry record. No calculated sample-size values or observed effect estimate are reported in the record.

Why does over-dispersion matter?

In general, over-dispersion means that observed variability exceeds what a statistical model assumes. It matters when a model’s standard errors and confidence intervals rely on an assumption of less variability than the data actually contain; underestimating variability can make uncertainty look smaller than it is. This concept is relevant to some count-data analyses, but the primary endpoint is a participant count for a binary response, and the record does not report a model or an over-dispersion assessment. No claim about over-dispersion or a model adjustment can be made for this study.

Multiplicity is another general consideration when a study has several outcomes or several analyses. Testing many outcomes can increase the chance of at least one apparently unusual finding, depending on the procedures and aims. The registry lists multiple outcome measures but no analyses and does not report a multiplicity strategy. It is therefore not possible to tell whether any adjustment was planned or performed.

Finally, statistical results depend on the analysis population and the treatment of missing observations. For example, a response proportion can change depending on whether its denominator includes all enrolled participants or only those with an evaluable assessment. Those choices should be specified rather than inferred. The registry record does not report the analysis populations or missing-data methods, and it does not post the primary response count needed to evaluate the endpoint.

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("Enasidenib Mesylat 100mg", "Enasidenib Mesylat 200mg")
n      <- c(2, 8)
events <- c(0, 0)
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  Enasidenib Mesylat 100mg  2  0  0.0  0.0  84.2  0.0  65.8  0.8  70.8
ARM  Enasidenib Mesylat 200mg  8  0  0.0  0.0  36.9  0.0  32.4  0.3  33.6

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary HI-E outcome and several secondary outcomes, including related adverse events, time to and duration of HI-E, platelet and neutrophil improvement, and red blood cell transfusion independence. It records seven outcome measures in total and no analyses. The registry record does not describe a multiplicity plan, such as whether any outcome was intended to be confirmatory, whether testing order was specified, or whether statistical significance thresholds were adjusted for multiple questions. The presence of several registered outcomes does not establish that all were analyzed or tested.

Missing-data handling is also not reported in the registry record. The primary endpoint is a participant count, but the record does not state how participants without a 16-week assessment were handled, whether an incomplete assessment could count as nonresponse, or whether a different analysis population was used. It does not report the primary endpoint denominator or the number of participants with available outcome measurements. Enrollment of 17 cannot substitute for those details.

The analysis populations are not reported in the registry record. It is therefore unknown whether the primary outcome was intended to include all enrolled participants, participants who received treatment, or participants with sufficient follow-up. No information is reported about protocol deviations, withdrawals, or exclusions from the efficacy analysis. These details affect how a response count should be interpreted and how representative it may be of all enrolled participants.

These are reporting gaps, not evidence that missing data or multiplicity were mishandled. Without the analysis plan and results, readers cannot assess the impact of missing assessments, identify which analyses were performed, or determine how the multiple outcomes were interpreted.

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: chest pain - cardiac (33.3%), duodenal hemorrhage (33.3%), sepsis (33.3%), lung infection (33.3%), adult respiratory distress syndrome (33.3%).

The registry reports adverse-event counts separately for Enasidenib Mesylat 100mg and Enasidenib Mesylat 200mg. In the 100mg group, 3 participants were at risk for serious adverse events and 3 were affected; 3 were at risk for other adverse events and 3 were affected. The record lists 1 death in that group. In the 200mg group, 14 participants were at risk for serious adverse events and 7 were affected; 14 were at risk for other adverse events and 14 were affected. The record lists 0 deaths in that group.

These are descriptive registry counts, not a randomized comparison. The record does not report event timing, duration, severity details beyond the serious/non-serious categories, or whether events were judged related to treatment. It also does not report how long participants were observed in each dose group. Differences in counts across the groups therefore should not be interpreted as dose-related risk differences.

The listed serious-event terms—Chest pain - cardiac, Duodenal Hemorrhage, Sepsis, Lung Infection, Adult Respiratory Distress Syndrome, and Syncope—are each accompanied by 33.3%. The registry record does not provide enough detail in these entries to establish whether terms occurred in separate participants, whether participants had more than one event, or the precise basis for each percentage. These terms and percentages should be read as reported, without treating them as a complete account of safety.

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

The study addresses a clinically relevant statistical question: whether participants with lower-risk MDS or non-proliferative CMML without an IDH2 mutation experience HI-E during enasidenib treatment. It is a phase Ib/II, single-center, open-label, single-arm study. The registry records an enrollment of 17 and specifies an HI-E endpoint with a timeframe of 16 weeks. These registry entries establish the scope and design of the registered question, not the answer to it.

The primary response count is not reported in the registry record. Without that count and its denominator, there is no posted response frequency to interpret and no way to assess its precision. The registry does not report a confidence interval or inferential analysis for the primary endpoint. The listed secondary outcomes similarly indicate outcomes of interest, but their results are not reported in the registry record.

Because there is no control group, any outcome observed in the study would be descriptive of the participants enrolled and assessed. A single-arm result cannot establish how those outcomes compare with a different treatment or with the outcomes that would have occurred without enasidenib. The open-label design and the absence of reported analysis details further limit what can be concluded from the record.

The posted safety counts document serious and other adverse events in the two named dose groups, as well as deaths. They do not, on their own, establish that events were caused by treatment or provide a comparative safety estimate. The groups are not described as randomized controls, and the registry does not report enough detail on event attribution or follow-up to support broader conclusions.

Accordingly, the registry record establishes that the study was completed and identifies its objectives, endpoint, design, and selected safety counts. It does not establish the size, precision, or comparative meaning of an HI-E response. The missing efficacy results should not be replaced by assumptions based on study aims, outcome definitions, or enrollment.

14. Why This Trial Matters Statistically

This trial illustrates why a clearly stated endpoint and a posted result are both needed for statistical interpretation. The registry defines HI-E as the primary outcome and gives response criteria tied to transfusion-burden categories. Yet the count of participants meeting that definition, the denominator assessed, and the uncertainty around any estimate are not reported in the registry record. A defined outcome without its observed result cannot answer the study’s primary efficacy question.

The design also highlights the distinction between describing outcomes and making a treatment comparison. A single-arm study can contribute descriptive evidence about participants who received the intervention, but it does not supply a randomized control group. That matters when interpreting changes in anemia, transfusion requirements, or other outcomes that may be affected by factors beyond treatment. The design label alone does not quantify any of those influences.

Another statistical issue is the relationship between registered outcomes and analyses. The record names a range of efficacy and safety measures, but reports no analyses. Knowing the outcomes of interest helps readers understand the study’s aims; knowing which analyses were conducted, which participants were included, and how missing observations were handled is necessary to evaluate results. Those analysis details are not reported in the registry record.

The safety entries further demonstrate why counts need context. Counts by dose group can document what was recorded, but without randomized allocation and details on exposure, follow-up, and event attribution, they do not support a direct dose comparison. The event terms and percentages are informative as registry entries, while still leaving important questions unresolved.

Statistically, the trial matters as an example of how design, outcome definition, analysis transparency, and result reporting work together. The available registry information makes the intended question visible, but absent primary results and analysis details, it cannot support a complete estimate of response or a comparative conclusion.

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 HI-E result. It also does not provide the denominator assessed, confidence interval, or analysis. Consequently, the primary outcome cannot be quantified from the posted record. Enrollment of 17 is recorded, but the number enrolled is not necessarily the number with an evaluable primary outcome.

The single-arm, open-label design limits comparative interpretation. No control group is listed, allocation is NA, and masking is none. The record therefore does not support a randomized comparison between enasidenib and another treatment or control. It also does not report details that would allow readers to assess how dose assignment or sequential escalation was implemented.

The endpoint description has details that are not reconciled in the registry record. Its timeframe is 16 weeks, while the NTD response definition refers to an observation period of 16 to 24 weeks. The LTB criterion is recorded as 0 units of red blood cell transfusions. The record does not clarify how this statement relates to the broader response definition or how the criteria were applied across categories. The criteria should therefore be read as registry wording, without adding an interpretation that is not documented.

Further limitations include absent information on missing-data handling, analysis populations, multiplicity, and the statistical analysis plan. The registry does not report the trial’s sample-size justification or interim analyses. The safety entries lack event timing, duration, attribution details, and a reported account of follow-up by group. These gaps restrict both efficacy and safety interpretation without implying that the study procedures were deficient.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Enasidenib in MDS &Non-proliferative Chronic Myelomonocytic Leukemia w/o IDH2 Mutation — NCT05282459.
• Registry record last updated 2026-09-03; status last verified 2026-04.
• Results first posted 2026-04-17.
• 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

NCT05282459 is registered as a completed phase Ib/II, single-center, open-label, single-arm study of enasidenib mesylate in people with lower-risk MDS or non-proliferative CMML without an IDH2 mutation. The registry lists enrollment of 17, a start date of 2022-01-12, and a primary completion date of 2024-12-03. The sponsor is Tian Yi Zhang.

The primary outcome is the number of participants achieving HI-E, with a timeframe of 16 weeks. Secondary outcomes include related adverse events, timing and duration of HI-E, platelet and neutrophil improvement, and red blood cell transfusion independence. The registry lists seven outcome measures and no analyses.

The record includes adverse-event counts for groups titled Enasidenib Mesylat 100mg and Enasidenib Mesylat 200mg, but does not report the primary efficacy result, its denominator, or an analysis plan. It also does not report missing-data methods, analysis populations, or a multiplicity strategy.