Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF (NCT01392443), a na phase 2 study. The primary outcome is Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24.

2. Clinical Question

The study’s stated objective was to assess ruxolitinib by measuring spleen-volume reduction in people with the listed forms of myelofibrosis. It also assessed safety and tolerability, patient-reported outcomes, and the duration of spleen-volume response. These are distinct questions: the primary endpoint concerns whether a prespecified threshold of spleen-volume reduction was reached at a particular assessment, while duration of response concerns how long a qualifying response persisted.

The registry identifies the study as a multinational, open-label Phase II study and lists enrollment of 120. The single-group structure means the primary question is descriptive of outcomes among treated participants. It does not, by itself, estimate how outcomes would differ under a separate treatment or control condition. The registry record does not report a numerical primary endpoint result, so the proportion meeting the threshold and the precision of that estimate cannot be described from this record.

3. Trial Design

This was a completed Phase II study of ruxolitinib in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. The registry describes the study as multinational, open-label, and single-group. Enrollment was 120. The record lists Novartis Pharmaceuticals as sponsor and gives the study start as 2010-10-14 and primary completion as 2017-10-31.

Single-group means the record does not describe a concurrently assigned control group. Open-label means the study was not masked; the masking field is listed as none. Allocation is listed as not applicable. These features make the design suitable for describing outcomes in the treated study group, but they do not provide the protection against confounding that random assignment to competing treatment groups can offer. There is no like-for-like control comparison in this study.

The intervention is listed as ruxolitinib, also referred to as INC424 in the title. The arm description says treatment was taken twice daily and describes starting doses according to baseline platelet count, but the dosing text is truncated in the registry record. Further dosing details, including complete dose-adjustment instructions, are not reported in the registry record.

The primary endpoint was assessed at 24 weeks and used the Full Analysis Set, defined as all patients who received at least one dose of ruxolitinib. The record describes magnetic resonance imaging as the method for measuring spleen size. Local radiologists were instructed not to provide quantitative spleen-volume measurements; scans were to be transferred for reading by a central reader.

The registry record does not report a detailed statistical analysis plan, a sample-size justification for the trial, or whether interim analyses were conducted. Planning illustrations based on the observed effect are not the study’s design rationale and should not be interpreted as observed power or as evidence that the study was designed around a particular effect.

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

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): comprised of all patients who received at least one dose of ruxolitinib.

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): comprised of all patients who received at least one dose of ruxolitinib.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With at Least 35% Reduction in Spleen Volume From Baseline at Week 24, measured over 24 weeks.

The primary endpoint was the percentage of participants with at least 35% reduction in spleen volume from baseline at week 24. It is a binary outcome at the participant level: each person either meets the stated reduction threshold at that assessment or does not. The endpoint therefore expresses the fraction of the analysis population reaching a prespecified degree of change, rather than the average change in spleen volume across participants.

Spleen volume was measured by MRI. According to the registry description, local radiologists were instructed not to provide a quantitative volume measurement, although they could provide qualitative assessments. Scans were to be read by a central reader after transfer from the site radiologist. This central reading approach is relevant because the endpoint depends on comparing spleen volume with baseline and deciding whether the specified threshold has been reached.

A threshold-based endpoint can make a response criterion explicit and clinically interpretable as a proportion of participants meeting that criterion. It also discards information about how far above or below the threshold each participant’s change lies. A participant just short of the threshold and one with little change are both counted as not meeting it, while participants with different reductions beyond the threshold are counted as responders alike. These are general properties of binary threshold endpoints, not additional findings from this study.

The registry reports the endpoint definition and its 24-week timeframe, but the numerical result, its denominator, and a confidence interval are not reported in the registry record. The endpoint is an imaging measure; it should not be read as a direct measure of every aspect of symptoms, quality of life, or other outcomes.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a single-group design estimate?

In general, a single-group study describes outcomes among participants who received the study intervention. It can estimate the frequency of an outcome in that group if the outcome count and relevant denominator are reported. It does not directly estimate a treatment contrast against a concurrent control group. This study is listed as single-group, with allocation not applicable and no masking. There is therefore no randomized comparison in the registry record against which to judge the primary endpoint.

For a causal comparison, the key quantity is usually a difference between outcomes under distinct treatment conditions. With no separate control group, that contrast is not available from this design. A before-and-after measure such as reduction from baseline can describe change, but a within-person change is not equivalent to the effect that would have occurred relative to a control condition. This is a general distinction between describing change and estimating a comparative treatment effect.

How should the primary endpoint be understood?

The endpoint is binary because each participant is classified according to whether the reduction meets the stated threshold at week 24. A response proportion is usually the number meeting the criterion divided by the number included in the relevant analysis. The registry defines the Full Analysis Set as patients who received at least one dose of ruxolitinib, but it does not give the primary endpoint count, percentage, or endpoint-specific denominator. Those numerical details are not reported in the registry record.

Binary endpoints are easy to express as a proportion, but they compress a continuous measurement into two categories. General statistical consequence: information about the amount of change within each category is not retained in the yes-or-no classification. The proportion depends on the selected threshold and assessment time. The threshold and time point are specified in the registry as at least 35% reduction at 24 weeks.

What would an uncertainty interval convey?

In general, a confidence interval communicates the uncertainty associated with an estimated quantity under a stated statistical model and method. For a response proportion, it would describe a range of values compatible with the observed data under that method. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The width is influenced by the amount of outcome information and by the observed response proportion. A confidence interval does not resolve bias, confounding, missing outcome data, or the absence of a comparison group.

The registry record does not report a confidence interval for the primary response. Without the endpoint estimate and its uncertainty, neither the size of the response proportion nor its precision can be assessed from the posted information. A p-value, if one were reported, would answer a different question about compatibility with a specified null model; it would not substitute for an effect estimate and interval.

Why does measurement and reading matter?

The registry describes MRI as the method for measuring spleen size. Local radiologists were instructed not to provide quantitative spleen-volume measurements, while central reading of transferred scans was planned. In general, central assessment can support consistency in applying measurement procedures across sites. The record does not give details of reader agreement, quality-control procedures, blinding of central readers, or the handling of scans that could not be evaluated. These details are not reported in the registry record.

The endpoint depends on comparison with baseline. Measurement variability at either assessment can affect classification around the threshold. This is a general consideration for endpoints based on change in an imaging measurement. The record describes the assessment approach but does not provide enough information to quantify measurement variability or its impact on the response classification.

What do planning illustrations mean?

General sample-size calculations estimate how much information a future study might need under specified assumptions. The record describes planning illustrations based on the observed effect, with two-sided significance level 0.05, equal allocation between two arms, and a normal approximation. The targeted effect is described as a stated fraction of the observed effect. These are planning assumptions for hypothetical comparisons, not evidence that this trial was designed as a two-arm study. The trial itself is listed as single-group.

For non-time-to-event illustrations, the stated convention is participants per arm. For time-to-event illustrations, the stated convention is the total number of events. These quantities are not interchangeable. A planning illustration is not observed power: observed power is not a measure of how convincing an observed result is, and a retrospective calculation based on an observed effect does not add information beyond the estimate and its uncertainty. The registry record does not report the trial’s own sample-size justification.

How should adverse-event counts be read?

In general, adverse-event summaries describe events or participants meeting event criteria during the defined reporting period. Seriousness is a regulatory classification, not a measure of whether an event was caused by a study intervention. Counts of participants with serious events and with other events may overlap, and event-term percentages may use a stated risk population as denominator. The registry’s safety figures should be interpreted as descriptive reporting in the treated group, not as a controlled estimate of treatment-attributable risk.

The record reports 120 participants at risk for the listed safety summaries, 60 affected by serious adverse events, 117 affected by other adverse events, and 13 deaths. Selected serious-event terms are reported with percentages. The record does not provide sufficient information to infer causation from these figures, and a comparison group is not available in this single-group 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("Ruxolitinib")
n      <- c(120)
events <- c(38)
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  Ruxolitinib  120  38  31.7  23.5  40.8  24.0  40.4  24.0  40.5

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and secondary outcomes that include the percentage of participants with at least 35% spleen-volume reduction at scheduled time points as best response, duration of response, change in EORTC QLQ-C30 scores from baseline at week 24, and change in total symptom score at week 24 measured by the seven-day modified MFSAF v2.0. These outcomes involve multiple measures and, for some, repeated assessment times. When several outcomes or time points are examined, the chance of at least one apparently unusual result can increase. In general, multiplicity procedures can address this issue by controlling how statistical evidence is interpreted across a family of tests.

Whether a multiplicity adjustment was planned or used is not reported in the registry record. The record also does not report a detailed statistical analysis plan, hierarchy among secondary endpoints, or which analyses were confirmatory versus exploratory. No adjustment method should be inferred from the listed outcome names alone.

The primary analysis population is the Full Analysis Set, defined as all patients who received at least one dose of ruxolitinib. The registry record does not report how many participants had evaluable MRI measurements at week 24, how missing or unevaluable scans were handled, or whether any imputation or sensitivity analyses were used. It also does not report the endpoint-specific denominator or the treatment of discontinuations before the assessment.

These omissions matter because a response proportion depends on who contributes endpoint information and how missing outcomes are handled. General methods may use different assumptions about participants without an observed endpoint; those assumptions can affect the estimate. Without a stated approach and outcome counts, the impact of missing data cannot be assessed. These details are not reported in the registry record, so interpretation must remain limited to the endpoint definition and analysis-population definition that are stated.

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: pneumonia (7.5%), pyrexia (6.7%), herpes zoster (5.0%), lung infection (5.0%), anaemia (4.2%).

The registry lists 120 participants at risk for each of the safety summaries. It reports 60 participants affected by serious adverse events, 117 affected by other adverse events, and 13 deaths. These are descriptive counts from the single ruxolitinib group. The groups of participants represented by the serious and other adverse-event counts may overlap; the record does not establish them as mutually exclusive categories.

The most frequently listed serious-event terms are pneumonia at 7.5%, pyrexia at 6.7%, herpes zoster at 5.0%, lung infection at 5.0%, anaemia at 4.2%, and cardiac failure at 2.5%. These percentages describe the registry’s selected serious-event terms. The record does not provide information about event timing, duration, severity beyond the serious classification, or whether individual participants experienced more than one listed term.

Serious adverse events and other adverse events are not interchangeable categories. Seriousness describes the event’s regulatory classification; it does not establish that the event was caused by treatment. The registry’s counts should not be read as causal estimates. With no separate control group, the safety figures do not show how event frequency would compare under another treatment condition. Attribution details and comparative safety estimates are not reported in the registry record.

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

The study addresses a defined statistical question: the proportion of treated participants with at least 35% reduction in spleen volume from baseline at week 24. It identifies the relevant disease groups, the intervention, the assessment method, and the Full Analysis Set definition. However, the numerical primary endpoint result is not reported in the registry record. The posted information therefore does not establish what proportion met the response threshold or how precisely that proportion was estimated.

Even if the primary response estimate were available, its interpretation would be shaped by the single-group, open-label design. A response observed among treated participants is not the same as a treatment effect estimated against a control group. Without a concurrent comparator, the study cannot isolate the difference attributable to treatment from other influences on outcome. This is a limitation of the design, not a judgment about the observed participants.

The primary endpoint is an imaging-based measure of spleen-volume change. It does not by itself summarize symptoms, quality of life, duration of response, or every safety outcome. The registry lists patient-reported outcomes and duration of response as secondary areas of assessment, but their numerical results are not reported in the registry record. Each outcome would need its own definition, estimate, and uncertainty to support interpretation.

The safety information documents serious and other adverse events and deaths in the treated group. It is descriptive and does not establish causation. Likewise, the listed serious-event percentages should not be interpreted as comparative excess risk, because the study has no control arm.

Thus, the registry record supports a description of the study’s purpose and methods, along with selected safety counts. It does not support a numerical characterization of the primary response, a comparative efficacy estimate, or a causal safety conclusion. Those boundaries are central to reading the posted results accurately.

14. Why This Trial Matters Statistically

This study illustrates how endpoint definition and design determine what a clinical result can answer. The primary measure is not simply any decrease in spleen volume; it is the proportion of participants reaching a stated threshold at a stated assessment time. That definition provides a clear response criterion, while also making the result dependent on classification around the threshold and on the availability of evaluable measurements.

The MRI reading process is another statistical feature of interest. Local radiologists were instructed not to quantify spleen volume, and scans were to be read centrally. Measurement procedures affect the data that enter an endpoint analysis, particularly when the outcome is based on change from baseline. The registry describes the intended reading pathway, although it does not report reader agreement or other measurement-quality results.

The single-group design makes the distinction between observed response and comparative effect especially important. Descriptive response data can characterize outcomes in the treated study group, but the lack of a concurrent control limits causal interpretation. This distinction applies even when an endpoint is objectively measured and clearly defined.

The record also shows why complete outcome reporting matters. A study can identify a primary endpoint, assessment time, and analysis population, yet readers still need the actual event count, denominator, estimate, and uncertainty to judge the result. Those primary numerical details are not reported in the registry record. As a result, the endpoint’s precision and magnitude cannot be evaluated from the posted information.

Finally, the safety summaries demonstrate the difference between counting events and comparing risks. Counts and percentages can describe what was recorded in one group, but they do not establish treatment attribution or relative risk without an appropriate comparison. The study is therefore useful as an example of interpreting study architecture, outcome definitions, and reporting completeness together rather than treating a single endpoint label as sufficient evidence.

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 principal limitation for interpretation is that the numerical result for the primary endpoint is not reported in the registry record. The record gives the endpoint definition, time point, and Full Analysis Set definition, but not the response count, percentage, endpoint denominator, or uncertainty interval. The magnitude and precision of the primary outcome therefore cannot be assessed.

The study is open-label and single-group, with no separate control condition. This limits comparative and causal interpretation of both efficacy and safety outcomes. Enrollment was 120, but that figure does not establish how many participants had evaluable week-24 imaging or contributed to each outcome. Endpoint-specific completeness is not reported in the registry record.

The registry describes MRI acquisition and central reading but does not report reader blinding, agreement, measurement reliability, or the handling of missing or unevaluable scans. The method for missing outcome data, including any imputation or sensitivity analysis, is not reported in the registry record. These details matter for a threshold-based endpoint because the classification depends on a measured change from baseline.

The record lists several secondary outcomes but does not report whether multiplicity was addressed, how outcomes were prioritized, or which analyses were confirmatory. A detailed statistical analysis plan, interim-analysis information, and the trial’s sample-size justification are not reported in the registry record. The dose description is truncated, so complete dosing and adjustment details are also not available in the record.

Safety counts are descriptive and come from a group without a control comparator. The record does not establish whether reported events were caused by treatment. Together, these limitations mean the registry information supports a description of the study and selected event counts, but not a full quantitative assessment of the primary outcome or a comparative estimate of treatment effects.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Asian Phase II Study of INC424 in Patients With Primary Myelofibrosis (MF), Post-PV MF or Post-ET MF — NCT01392443.
• Registry record last updated 2019-09-03; status last verified 2019-08.
• Results first posted 2019-09-03.
• 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

NCT01392443 is a completed, multinational, open-label, single-group Phase II study of ruxolitinib, also called INC424, in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocythemia myelofibrosis. Enrollment was 120. The primary endpoint was the percentage of participants with at least 35% reduction in spleen volume from baseline at week 24, assessed by MRI. The Full Analysis Set comprised patients who received at least one dose of ruxolitinib.

The registry reports 60 participants affected by serious adverse events, 117 affected by other adverse events, and 13 deaths among 120 at risk. The numerical primary endpoint result, its denominator, and its uncertainty are not reported in the registry record. The single-group design does not provide a concurrent control comparison, and causal attribution of safety events is not established by the posted counts.