This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations. (NCT02598297), a randomized phase 3 study. The primary outcome is Progression Free Survival (PFS-1).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02598297 |
| Phase | Phase 3 |
| Condition | Myelofibrosis With High Molecular Risk Mutations |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 49 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
People with early myelofibrosis and high molecular risk mutations. The registry record describes a Full Analysis Set as all subjects randomized to a study treatment.
Intervention
Ruxolitinib: two tablets of 5 mg taken orally twice per day.
Comparator
Ruxolitinib placebo: two tablets of 5mg taken orally twice per day.
Primary question
Would progression-free survival, measured from randomization to disease progression or death, be evaluated between randomized treatment groups?
The trial was designed to investigate efficacy and safety in a population characterized in the registry summary as having high molecular risk mutations and early myelofibrosis. Its primary endpoint was progression-free survival, termed PFS-1. The endpoint was intended to capture the time from randomization until any listed disease-progression criterion or death from any cause.
The registry record does not report a treatment-effect estimate for this question. It states that the study was terminated and that the primary endpoint and other time-to-event endpoints were not derived under the statistical analysis plan. Consequently, the record does not establish whether the groups differed in progression-free survival or how precisely any such difference could have been estimated.
3. Trial Design
This was a randomized, double-blind, placebo-controlled, multicenter phase III study with a parallel-group model and triple masking recorded in the registry. The study began on 2016-02-03, and primary completion was recorded as 2017-10-23. Its status is terminated. The enrollment figure is 49.
One group was assigned ruxolitinib, described as two 5 mg tablets taken orally twice per day. The comparator group received two 5mg placebo tablets orally twice per day. Randomization and masking are design features intended to reduce systematic differences in treatment assignment and assessment. The registry record does not report the allocation ratio, the randomization procedure, or which parties were included in the recorded masking designation.
The record lists 24 participants at risk for adverse-event reporting in each group. Those figures are adverse-event denominators, not a complete accounting of how the enrollment figure was distributed. The record does not explain the relationship between the enrollment total and these group-specific denominators, so they should not be reconciled by assumption.
The study was terminated, but a reason for termination is not reported in the registry record. The protocol’s planned recruitment target, the rationale for that target, and whether recruitment or follow-up stopped earlier than intended are also not reported in the registry record. The registry describes an intended assessment period for the primary endpoint as from randomization until progression, estimated to be assessed up 48 months; it does not provide a completed follow-up summary.
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
| Stage | Ruxolitinib (INC424) | Ruxolitinib Placebo |
|---|---|---|
| STARTED | 25 | 24 |
| Not Treted Wit Study Drug | 1 | 0 |
| Subjects Followed for Survival | 1 | 0 |
| COMPLETED | 0 | 0 |
| NOT COMPLETED | 25 | 24 |
Reasons for not completing this period:
| Reason | Ruxolitinib (INC424) | Ruxolitinib Placebo |
|---|---|---|
| Study terminated by Sponsor | 21 | 23 |
| Adverse Event | 1 | 1 |
| Physician Decision | 1 | 0 |
| Subject/guardian decision | 1 | 0 |
| Followed for survival | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) included all subjects who were randomized to a study treatment. This endpoint was not analyzed as study was terminated and it was specified in the statistical analysis plan (SAP) that the primary endpoint of PFS and any other time to event endpoint would not be derived.
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: The Full Analysis Set (FAS) included all subjects who were randomized to a study treatment.
| Characteristic | Unit | Ruxolitinib (INC424) | Ruxolitinib Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 25 | 24 | 49 | |
| Age, Continuous | Years | 59.0 (SD 14.23) | 67.4 (SD 7.72) | 63.1 (SD 12.17) |
| Sex: Female, Male: Female | Participants | 12 | 7 | 19 |
| Sex: Female, Male: Male | Participants | 13 | 17 | 30 |
| Race/Ethnicity, Customized: Caucasian | Participants | 19 | 23 | 42 |
| Race/Ethnicity, Customized: Asian | Participants | 4 | 1 | 5 |
| Race/Ethnicity, Customized: Other | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Missing | Participants | 1 | 0 | 1 |
6. Primary Endpoint
The registry lists the primary outcome as Progression Free Survival (PFS-1), measured over From randomization till disease progression (estimated to be assessed up 48 months).
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was PFS-1, or progression-free survival from randomization. It was defined as the time until the first occurrence of any listed disease-progression criterion or death from any cause. The criteria included progressive splenomegaly, circulating peripheral blast counts > 10%, leukemic transformation, hemoglobin < 10g/dl with an absolute decrease of at least 3 g/dl from baseline, white blood cell counts > 25 x 103/ μL, and an MF-7 score ≥ 30. Death from any cause was also included as an event.
Time-to-event endpoints are generally used to account for both whether an event occurs and when it occurs. They can describe the course of an outcome over follow-up, while allowing the analysis to handle participants whose event status is not observed for the full period through appropriate censoring methods. That general advantage depends on having usable event and follow-up data and a prespecified analysis.
For this study, the registry record states that PFS-1 was not analyzed. Because the endpoint was not derived, the record contains no reported comparison of progression-free survival between treatment groups and no estimate of the timing or frequency of progression events.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The main statistical fact is that the planned primary endpoint does not have a reported analysis in the registry record. The record explicitly says that the study was terminated and that PFS and other time-to-event endpoints would not be derived, as specified in the statistical analysis plan. The registry lists zero analyses. There is therefore no primary endpoint estimate, confidence interval, or hypothesis-test result to interpret.
This is different from a trial result showing no difference. A finding of no statistically detectable difference would require an analysis of outcome data and would still need to be interpreted in light of the estimate’s uncertainty. Here, the endpoint was not analyzed, so the posted record cannot answer whether the groups had similar or different progression-free survival. It also cannot show the size or direction of a treatment effect on that endpoint.
The enrollment figure is 49, and the adverse-event groups each list 24 participants at risk. Neither figure supplies the missing time-to-event analysis. The record does not report event counts, censoring information, follow-up distributions, hazard ratios, or confidence intervals for PFS-1. Those details should not be inferred from enrollment or from safety counts.
The record does contain safety counts. Two participants in the ruxolitinib group and one in the placebo group were recorded as affected by serious adverse events, with 24 at risk in each group. These descriptive counts do not substitute for an efficacy analysis. They also do not, on their own, establish a comparative safety effect: interpretation would depend on event definitions, timing, exposure, completeness of reporting, and uncertainty, none of which is fully characterized in the posted summary.
The registry lists 11 outcome measures, including secondary outcomes such as time to primary progression, spleen-volume change, symptom change, overall survival, and quality-adjusted life years. The record lists no analyses for these outcomes. Their presence as listed measures does not mean that results were calculated or reported. Overall, the posted data describe the study design and some adverse-event counts, but they do not provide an analyzed efficacy result.
9. Statistical Methods Explained
Randomization assigns participants to study groups using a chance-based process. In general, it is intended to balance both measured and unmeasured prognostic factors across groups over repeated trials. That benefit is a property of the design, not a guarantee that groups will be balanced in any particular small study. The registry identifies this study as randomized but does not report the allocation sequence, allocation ratio, or procedures used to conceal assignment.
What a time-to-event analysis would estimate
In general, a time-to-event analysis uses the elapsed time from a defined starting point to an event. For PFS-1, the recorded starting point was randomization, and the event definition combined specified progression criteria with death from any cause. Combining several criteria creates a composite endpoint: the first qualifying event determines the endpoint time. A composite can capture several ways in which disease progression may be recognized, but its interpretation depends on knowing which components occurred and how each was defined and assessed.
Participants may have incomplete observation. In general, censoring records that an event was not observed by the last available follow-up time; it does not mean that the participant remained event-free after that point. Standard time-to-event methods use available follow-up under assumptions about censoring. The registry record does not report event counts, censoring details, follow-up distributions, or an endpoint analysis for this trial. It therefore does not permit an assessment of those assumptions or a reconstruction of the primary analysis.
How treatment groups are commonly compared
In general, a time-to-event trial may report survival curves, a comparison test, and an effect estimate such as a hazard ratio with a confidence interval. A confidence interval describes the range of estimates reasonably compatible with the data under the method’s assumptions; it conveys precision as well as direction. A hypothesis-test result alone would not describe the size or precision of an effect. These are general features of common analyses, not methods reported as used in this trial.
The registry record does not report a PFS-1 estimate, confidence interval, p-value, survival curve, or event count. It states that the primary endpoint and other time-to-event endpoints were not derived because the study was terminated and this was specified in the statistical analysis plan. No particular statistical test, model, covariate adjustment, or censoring rule for the intended primary analysis is reported in the registry record.
Why the planned analysis matters
A prespecified analysis plan helps determine how outcomes will be defined, compared, and reported before results are known. It can specify the analysis population, treatment contrast, handling of missing observations, and methods for multiple outcomes. The registry record says that the decision not to derive PFS and other time-to-event endpoints was specified in the statistical analysis plan. Further details of that plan are not reported in the registry record, so the intended estimator and any planned sensitivity analyses cannot be described.
The Full Analysis Set is described as including all subjects randomized to a study treatment. In general, an analysis based on randomized assignment aims to preserve the comparison created by randomization, even if participants do not follow treatment exactly as planned. The record supplies the population definition but reports no endpoint analysis using it. The number of participants included in any efficacy analysis, and reasons for any exclusions or missing outcome data, are not reported in the registry record.
Precision and planning illustrations
In general, precision depends on the amount of information available, not only on the total number enrolled. For a time-to-event endpoint, event information and observed follow-up are important to the precision of a treatment comparison. A planning calculation can illustrate the sample size or event total that might be needed under stated assumptions, but it is not evidence that a study had that size or that its result would be precise. It is also not observed power, which cannot replace an effect estimate and its uncertainty.
The record’s planning assumptions describe two-sided significance level 0.05, equal allocation, and a normal approximation, with the detectable effect expressed as a fraction of the observed effect. For time-to-event illustrations, the stated quantity is total events using the Schoenfeld method; for other outcomes, it is participants per arm. These are planning conventions, not the reported design justification for this trial. The actual sample-size justification and its assumptions are not reported in the registry record. Moreover, no primary endpoint analysis is posted from which an observed PFS effect can be interpreted.
Over-dispersion is a general issue for count outcomes when variability exceeds what a simple model assumes. It can make standard errors too small if ignored. This is not a reported feature of the trial’s primary endpoint, which is time-to-event, and no count-outcome model is reported in the registry record. Likewise, no model-based treatment estimate should be attributed to this study based on general statistical practice alone.
10. Multiplicity, Missing Data and Analysis Populations
Multiplicity arises when several outcomes, time points, or statistical comparisons are tested. In general, the more opportunities there are to obtain a nominally unusual result, the more important it is to know whether testing was adjusted or hierarchically organized. The registry lists 11 outcome measures, with PFS-1 as primary and several secondary measures, including time to primary progression, spleen-volume change, symptom change using MF-7, EQ-5D subscale scores, overall survival, plasma ruxolitinib concentrations, PFS-2, and quality-adjusted life years. The record lists zero analyses, so it supplies no result set in which multiplicity adjustment or selective reporting can be evaluated.
The primary endpoint was not derived, and other time-to-event endpoints were also not derived, according to the registry record. The record does not report whether analyses of other outcomes were conducted outside the posted registry results. The statistical plan’s broader approach to multiplicity is not reported in the registry record.
Missing-data handling is also not reported in the registry record. The Full Analysis Set is defined as all subjects randomized to a study treatment, but the record does not give endpoint-specific participant counts, missingness patterns, reasons for missing data, or imputation methods. For time-to-event outcomes, incomplete follow-up and censoring require explicit definitions; those details are unavailable because no endpoint analysis was derived.
Without analysis results and these supporting details, readers cannot assess how many participants contributed information to each outcome, whether missingness could have affected estimates, or whether multiple testing was controlled. Those are limitations of what can be concluded from the registry record, not evidence that any particular analytical practice was or was not followed beyond the stated decision not to derive the time-to-event endpoints.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Ruxolitinib (INC424) | 2 | 24 | 8.3% |
| Ruxolitinib Placebo | 1 | 24 | 4.2% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Ruxolitinib (INC424) | 0 of 24 |
| Ruxolitinib Placebo | 0 of 24 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Ruxolitinib (INC424) | 17 of 24 |
| Ruxolitinib Placebo | 11 of 24 |
Most frequent serious adverse event terms
| Event term | Organ system | Ruxolitinib (INC424) | Ruxolitinib Placebo |
|---|---|---|---|
| Tendon rupture | Injury, poisoning and procedural complications | 1 of 24 | 0 of 24 |
| Gastric cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 1 of 24 | 0 of 24 |
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | 0 of 24 | 1 of 24 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Ruxolitinib (INC424) | Ruxolitinib Placebo |
|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 7 of 24 | 6 of 24 |
| Fatigue | General disorders | 3 of 24 | 4 of 24 |
| Hypertension | Vascular disorders | 3 of 24 | 3 of 24 |
| Nasopharyngitis | Infections and infestations | 4 of 24 | 0 of 24 |
| Upper respiratory tract infection | Infections and infestations | 3 of 24 | 0 of 24 |
| Cough | Respiratory, thoracic and mediastinal disorders | 3 of 24 | 0 of 24 |
| Night sweats | Skin and subcutaneous tissue disorders | 1 of 24 | 2 of 24 |
| Pruritus | Skin and subcutaneous tissue disorders | 0 of 24 | 3 of 24 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 24 | 2 of 24 |
| Pyrexia | General disorders | 2 of 24 | 0 of 24 |
Serious events with the highest arm-level rate: tendon rupture (4.2%), gastric cancer (4.2%), pneumonitis (4.2%).
The serious adverse-event figures are counts of participants reported as affected, alongside the number at risk. The ruxolitinib group lists 2 affected among 24 at risk; the ruxolitinib placebo group lists 1 affected among 24 at risk. The record lists zero deaths in each group. These figures are descriptive counts, not adjusted comparative estimates, and they do not include a confidence interval or statistical test in the registry record.
The most frequent serious adverse-event terms listed are tendon rupture, gastric cancer, and pneumonitis, each reported as 4.2%. The record does not assign these terms to a specific treatment group in the posted summary, so they should not be attributed to either group. The percentages are quoted as reported and should not be converted into additional counts by assumption.
Other adverse events affected 17 participants in the ruxolitinib group and 11 in the placebo group, with 24 at risk in each. The registry summary does not provide event-level detail or exposure-adjusted rates. Counts can be affected by follow-up duration, ascertainment, and the number of events per participant. The posted figures alone do not establish a causal relationship or provide a complete comparative safety assessment.
12. What the Result Does, and Does Not, Mean
The registry record establishes that a randomized, masked, placebo-controlled phase III study was conducted in early myelofibrosis with high molecular risk mutations, and that the study status is terminated. It describes ruxolitinib and placebo regimens and identifies progression-free survival as the primary endpoint. It also reports adverse-event counts for the two groups.
It does not establish an efficacy result. The primary endpoint was not analyzed, and the registry states that the endpoint and other time-to-event outcomes would not be derived under the statistical analysis plan. No estimate or measure of precision is reported for PFS-1. It is therefore not possible to conclude from this record that ruxolitinib improved, worsened, or had no effect on progression-free survival relative to placebo.
Absence of a reported analysis is not the same as evidence of no difference. A null or inconclusive result requires an analyzed comparison; the posted record does not contain one. Nor can the enrollment figure or adverse-event counts fill this gap. Those data address aspects of the study conduct and safety reporting, not the missing primary efficacy estimate.
The safety counts should also be read within their limits. They describe affected participants in the reported risk groups, but the registry does not provide a comparative model, uncertainty intervals, detailed exposure information, or group assignment for the listed serious-event terms. The figures are not sufficient by themselves to establish whether the treatments differ in safety.
The defensible conclusion is narrow: the registry documents the study design, planned endpoint, termination status, and some posted safety information, while leaving the primary efficacy question unanswered. Any broader conclusion about treatment benefit, lack of benefit, or the reasons for termination would go beyond what is reported in the registry record.
13. Why This Trial Matters Statistically
This trial is statistically notable because it illustrates the distinction between a well-defined endpoint and an analyzed endpoint. PFS-1 is described with a time origin and a set of progression events, including death. That definition clarifies what the study intended to measure. Yet a clearly defined outcome cannot support a treatment comparison when the record states that it was not derived.
The randomized, placebo-controlled design would ordinarily support a between-group comparison by reducing confounding from treatment assignment. But randomization does not itself produce an efficacy estimate. Interpretation still requires outcome information, a specified analysis, and a measure of uncertainty. The record contains none of these for the primary endpoint.
The trial also highlights why registry status and results need to be read together. The study is recorded as terminated, and the primary and other time-to-event endpoints were not analyzed. This matters because readers might otherwise mistake the existence of a phase III design and a primary endpoint definition for evidence that an efficacy comparison was completed. The registry record makes clear that those are not equivalent.
Finally, the posted safety counts demonstrate the importance of distinguishing descriptive reporting from comparative inference. Counts and event terms can describe what was recorded, but without information about timing, exposure, uncertainty, and a prespecified comparison, they do not resolve treatment differences. In this record, the clearest statistical contribution is transparency about the missing primary analysis and the boundaries of what the available results can support.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation is that the primary PFS-1 endpoint was not analyzed. The registry explicitly attributes the absence of derived time-to-event endpoints to study termination and the statistical analysis plan. As a result, no treatment-effect estimate, confidence interval, p-value, event count, or survival curve for the primary outcome is reported.
The reason for termination is not reported in the registry record. The actual sample-size justification, recruitment target, allocation ratio, detailed statistical methods, and any planned sensitivity analyses are also not reported in the registry record. The record gives an intended timeframe for assessment but does not report completed follow-up or the distribution of follow-up time.
The enrollment figure is 49, while each adverse-event group lists 24 participants at risk. The registry summary does not explain the relationship between these figures. They should be quoted as recorded without inferring how the enrollment total was allocated or whether any participant lacked safety follow-up.
The record lists 11 outcome measures but no analyses. It does not report whether outcomes beyond the un-derived time-to-event endpoints were analyzed elsewhere, nor does it provide endpoint-specific analysis populations or missing-data handling. The serious-event terms are not assigned to a treatment group in the summary. These gaps limit both efficacy interpretation and a detailed safety comparison.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Phase III Study Investigating the Efficacy and Safety of Ruxolitinib in Early Myelofibrosis Patients With High Molecular Risk Mutations. — NCT02598297.
- Registry record last updated 2019-08-16; status last verified 2019-07.
- Results first posted 2019-08-16.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02598297 is a randomized, double-blind, placebo-controlled, multicenter phase III parallel-group study of ruxolitinib in early myelofibrosis with high molecular risk mutations. Enrollment is 49; the study began on 2016-02-03, primary completion was 2017-10-23, and the recorded status is terminated.
The primary endpoint was progression-free survival from randomization, defined by specified progression criteria or death. The registry record states that this endpoint and other time-to-event outcomes were not derived under the statistical analysis plan. It lists 11 outcome measures and zero analyses.
Safety reporting lists 24 participants at risk in each group, serious adverse events affecting 2 in the ruxolitinib group and 1 in the placebo group, and zero deaths in both groups. The reason for termination and the primary efficacy result are not reported in the registry record.