Efficacy and Safety of P1101 in Polycythemia Vera Patients for Whom the Standard of Treatment is Difficult to Apply: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of P1101 in Polycythemia Vera Patients for Whom the Standard of Treatment is Difficult to Apply (NCT04182100), a na phase 2 study. The primary outcome is Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12.

2. Clinical Question

The clinical question concerns whether participants in this study met a defined combination of blood-count criteria at both assessment times while remaining free of phlebotomy over the specified preceding period. The endpoint is a proportion: it describes the share of the studied group who satisfied every component of the response definition, rather than the average change in one laboratory measure.

The intervention was not P1101 in isolation. The registry describes treatment with phlebotomies and low-dose aspirin alongside P1101. As a result, the study addresses outcomes during this treatment approach; its design cannot separate the contribution of P1101 from the other components or from changes that might occur over time.

The registry record does not report the number or proportion who met the primary endpoint. It therefore identifies the question and the criteria used to define a responder, but does not show the observed response rate or its precision. The single-group design also means that the study does not directly estimate how outcomes compare with a separate control group.

3. Trial Design

This was a Phase 2, single-arm study of P1101 in patients with polycythemia vera. The registry lists an enrollment of 29 and describes the participants as adult Japanese patients for whom the standard of treatment was difficult to apply. The study is marked completed. Its listed start date is 2019-12-20, and its primary completion date is 2021-03-08.

The registry describes a single treatment group rather than randomized allocation or a masked comparison. Participants received conventional treatment based on phlebotomies and low-dose aspirin, together with subcutaneous pegylated proline-interferon alpha-2b (P1101, ropeginterferon alfa-2b) once every 2 weeks. The low-dose aspirin range stated in the treatment description is 75-150 mg/day.

Because there was no separate control group, the study can describe outcomes among participants receiving the specified treatment approach, but it cannot provide a randomized between-group estimate. Changes from baseline, if reported, would describe within-group change; they would not by themselves establish what would have happened under another treatment or without P1101.

The primary endpoint is framed around response at Months 9 and 12, with no phlebotomy in the preceding 3 months at each assessment. The registry also names secondary outcomes covering blood counts, spleen size, time to requiring no phlebotomy, time to first response, response maintenance, and thrombotic or hemorrhagic events. The registry record does not report a statistical analysis plan, details of masking beyond the listed absence of masking, or further information about how participants were selected. Those details are not reported in the registry record.

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: Eligible patients were to be treated with P1101, starting at 100 μg (or 50 μg in patients under another cytoreductive therapy). The dose was to be gradually increased by 50 μg every 2 weeks (in parallel, other cytoreductive therapy should be decreased gradually, as appropriate) until stabilization of the hematological parameters is achieved (hematocrit \<45%, platelet count ≤400 × 10\^9/L, and leukocyte count ≤10 × 10\^9/L). The maximum recommended single dose is 500 μg injected every 2 weeks.

Overall Study

Reasons for not completing this period:

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 Proportion of Subjects Who Achieved Durable Phlebotomy-free Complete Hematological Response (CHR) at Month 12, measured over 12 months.

The primary endpoint is the proportion of participants who achieved durable phlebotomy-free complete hematological response at Month 12. The description defines a responder as meeting the required criteria at both Months 9 and 12 and having no phlebotomy during the 3 months before each assessment. The listed criteria are hematocrit below 45% without phlebotomy, platelet count ≤400 × 10^9/L, and leukocyte count ≤10 × 10^9/L.

This composite endpoint combines blood-count thresholds with a treatment-use condition and requires the response to be present at two assessment times. It is intended to capture a sustained pattern rather than a single favorable measurement. A participant who did not meet any one component would not satisfy the stated responder definition.

A proportion is useful for expressing how often a defined response occurred in the studied group. Its interpretation depends on both the response definition and the completeness of outcome assessment. The registry record identifies the endpoint and its timeframe but does not report the observed responder count, the proportion, or a confidence interval. The endpoint definition can therefore be described, but the result and its statistical precision cannot be evaluated from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes a binary primary outcome: each participant either met the complete responder definition or did not. The endpoint is expressed as a proportion of participants, and its criteria require phlebotomy-free status and specified blood-count levels at both Months 9 and 12. The registry names the endpoint but does not report the response count, the proportion, or an analysis estimate.

What does a single-group design estimate?

In general, a single-group study can describe outcomes observed among the people who received the study treatment approach. If an outcome is measured at baseline and later follow-up, the analysis may also describe within-person or within-group change, depending on the methods used. Such descriptions do not create a control group. Without a concurrent comparison group, it is not possible to distinguish the treatment-associated outcome from all other influences on the observed course.

That distinction is especially relevant because P1101 was given alongside conventional treatment based on phlebotomies and low-dose aspirin. A result from the group would relate to the combined treatment context recorded in the registry. The design would not by itself identify the separate effect of P1101, or quantify how outcomes would differ under another treatment strategy.

How should a binary response be read?

For a binary endpoint, the response count indicates how many participants met the definition, while the denominator indicates how many were included in the analysis. A proportion puts that count in relation to its denominator. The denominator can depend on the analysis population and on how missing assessments are handled. Those analysis details, including the denominator for the primary outcome, are not reported in the registry record.

A confidence interval is a general statistical way to express uncertainty around an estimate. For a response proportion, its width depends in part on the amount of information available and on the observed response pattern, as well as the method used to calculate it. A confidence interval does not remove possible bias from the study design, incomplete follow-up, or outcome measurement. The registry record does not report a confidence interval for the primary endpoint.

Why does the endpoint require repeated response?

The responder definition requires the criteria to be met at both Months 9 and 12 and includes a restriction on phlebotomy in the preceding 3 months. Requiring response at more than one assessment is a way to define persistence rather than counting a qualifying measurement at only one time. It also makes the endpoint dependent on assessments at both times. In general, if an assessment is unavailable, the analysis needs a prespecified rule for classifying or handling that participant. The registry record does not report such a rule.

What does the registry say about statistical analyses?

The registry lists no analyses. It does not report an estimation method, hypothesis test, model, adjustment strategy, or plan for the primary endpoint. It also does not describe an interim analysis or a sample-size justification. These items are not reported in the registry record, so the analysis choices should not be inferred from the endpoint definition or from the study phase.

The registry lists secondary outcomes involving changes in hematocrit, white blood cell count, platelet count, and spleen size, as well as time-to-event and event-proportion outcomes. Different outcome types can require different statistical methods. In general, continuous measurements are often summarized using a measure of location and variability; binary outcomes are described using counts and proportions; and time-to-event outcomes account for the timing of an event and may also need to account for participants whose event status is not observed by the end of follow-up. Those are general method descriptions, not claims about the methods used in this study.

Why can multiple outcomes affect interpretation?

When a study assesses multiple outcomes, the chance of finding at least one apparently notable result can increase if many statistical tests are performed. Statistical methods can address multiplicity in several ways, but the approach depends on the planned questions and analysis. The registry does not report which, if any, multiplicity strategy was used. It also does not report analysis results for the listed outcomes. Therefore, no adjustment or hierarchy among outcomes can be assumed.

The registry includes planning-illustration assumptions elsewhere, but planning calculations are not observed study results or evidence that a trial had a particular probability of detecting an effect. In general, a planning illustration depends on its assumptions and should not be read as observed power. The registry record does not report a sample-size justification or the statistical planning method used for this study.

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("P1101")
n      <- c(29)
events <- c(8)
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  P1101  29  8  27.6  12.7  47.2  14.7  45.7  14.7  45.9

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and several secondary outcomes, including laboratory changes, spleen size, time-to-event outcomes, and the proportion without thrombotic or hemorrhagic events. It does not report a statistical analysis plan describing the order of testing, which outcomes were confirmatory, or whether any adjustment for multiple comparisons was used. The approach to multiplicity is therefore not reported in the registry record.

Multiplicity matters because, in general, examining many outcomes or conducting many statistical tests can increase the chance of a seemingly notable finding arising by chance. The implications depend on the analyses actually performed and the questions designated in advance. The registry lists no analyses, so the reported record does not support an assessment of the multiplicity consequences for this study.

The registry also does not report how missing outcome assessments were handled, whether participants who discontinued treatment remained in the efficacy analysis, or which analysis population was used. These details are important for interpreting a proportion: the response count must be understood alongside the denominator and the rules used when outcome status is unavailable. The record does not give those details for the primary endpoint.

Likewise, details of imputation, exclusions, or sensitivity analyses are not reported in the registry record. No approach should be assumed. Since no primary efficacy estimate is reported, the effect of missing data on that result cannot be assessed. The record’s endpoint definition specifies the assessments and response criteria, but does not describe how incomplete assessment at either time would affect classification.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry safety summary lists 29 participants at risk for serious adverse events and 0 participants with a serious adverse event. It lists 29 participants at risk for other adverse events and 29 participants with other adverse events. The death count is 0. These are participant counts in the registry record, not comparisons between treatment groups.

The record does not list serious adverse-event terms, and it does not provide a detailed breakdown of the other adverse events in this summary. It therefore does not show which events occurred, their severity, timing, duration, or whether they were considered related to treatment. Those details are not reported in the registry record.

In general, safety counts require context. The number of participants with an event is different from the number of event episodes, and neither alone describes the full clinical importance of events. A single-group study also cannot establish comparative safety against a control group. The listed figures should be read as the registry’s reported participant counts, not as evidence of a comparative risk or a complete account of all safety details.

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

The study asks a focused question about whether participants receiving P1101 with conventional treatment met a sustained, phlebotomy-free complete hematological response definition at two specified assessment times. The registry states the response criteria and identifies the study as completed. It also reports enrollment of 29 participants.

However, the registry record does not report the number or proportion of participants who achieved the primary endpoint. It therefore does not establish how often the defined response occurred or how precisely that frequency was estimated. The outcome definition alone cannot be used to infer the result.

Even if a response estimate were available, the single-group design would describe outcomes in this treatment group rather than provide a randomized estimate of how treatment compares with an alternative. Because P1101 was administered alongside phlebotomies and low-dose aspirin, the design also cannot isolate the contribution of P1101 from the full treatment approach.

The safety summary reports 0 participants with serious adverse events, 29 with other adverse events, and 0 deaths. The registry does not provide a detailed event listing in this summary, so these counts do not give a complete picture of event types or severity. They also do not compare safety with another group.

The most defensible interpretation is therefore limited to what the registry records: the study design, treatment context, endpoint definition, and safety counts. The primary efficacy result, analysis details, missing-data handling, and comparative evidence are not reported in the registry record. The study description should not be mistaken for a demonstrated treatment effect or a comparison with usual care.

14. Why This Trial Matters Statistically

This study is statistically notable for the combination of a clearly specified binary response endpoint and a single-group design. The endpoint is not simply a blood-count measurement at one visit: it requires several criteria at both Months 9 and 12 and includes a period without phlebotomy before each assessment. That definition makes the clinical question precise, while also making its analysis dependent on having the required assessments and a clear rule for incomplete data.

The design determines the kind of inference that can be made. A single group can provide a description of observed outcomes under the treatment approach used. It does not provide a randomized contrast, so a response proportion cannot be interpreted as the difference attributable to P1101 compared with another strategy. This distinction is central when reading outcomes from a study without a control group.

The record also illustrates the difference between registering an endpoint and reporting its result. Here, the endpoint definition is available, but the observed response count, proportion, and uncertainty interval are not reported. Without those, readers cannot assess the size or precision of the primary outcome. A well-defined measure is necessary for interpretation, but it does not substitute for outcome data.

Finally, the registry lists other outcome domains but no analyses. This leaves uncertainty about how those outcomes were handled, how missing data were addressed, and whether multiplicity was considered. These are not merely technical details: they determine how strongly results can support a statistical interpretation. The available record is useful for understanding the intended question and study structure, but incomplete for evaluating the primary efficacy result.

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 central limitation for interpreting efficacy is that the registry record does not report the primary endpoint result. It gives the response definition but not the number of participants who met it, the analysis denominator, or an estimate of uncertainty. The response frequency and its precision therefore cannot be evaluated from the registry record.

The single-group design provides no concurrent comparison group. Consequently, outcomes among participants cannot be directly contrasted with outcomes under another treatment, and the design cannot separate the contribution of P1101 from the accompanying use of phlebotomies and low-dose aspirin. The registry also does not report an analysis plan or the methods used to estimate outcomes.

The recorded enrollment is 29. Results from a study of this size, if available, would need to be interpreted with attention to the uncertainty around estimates; however, the registry does not report the primary estimate or its interval. No statistical precision can be inferred from enrollment alone.

The record does not report missing-data rules, analysis populations, participant flow, or sensitivity analyses. It also does not describe how multiple outcomes were handled statistically. These omissions limit evaluation of whether the analyses followed prespecified methods and how incomplete follow-up might affect the findings.

The study concerns adult Japanese patients described as having difficulty applying the current standard of treatment. The registry record does not provide further details about participant selection or characteristics. Applicability to other populations or treatment settings cannot be assessed from the information recorded. Safety interpretation is also limited by the lack of event-level detail in the registry summary.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Efficacy and Safety of P1101 in Polycythemia Vera Patients for Whom the Standard of Treatment is Difficult to Apply — NCT04182100.
• Registry record last updated 2025-09-15; status last verified 2021-12.
• Results first posted 2025-09-15.
• 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

NCT04182100 is a completed Phase 2, single-group study of P1101 in adult Japanese patients with polycythemia vera for whom the standard of treatment was difficult to apply. The registry lists enrollment of 29, a start date of 2019-12-20, and a primary completion date of 2021-03-08.

The treatment description combines subcutaneous P1101 once every 2 weeks with conventional treatment based on phlebotomies and low-dose aspirin. The primary endpoint is durable phlebotomy-free complete hematological response at Month 12, defined using assessments at both Months 9 and 12.

The registry record does not report the primary endpoint result or any statistical analyses. Its safety summary lists 0 participants with serious adverse events, 29 with other adverse events, and 0 deaths. Detailed event terms and analysis methods are not reported in the registry record.