Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP) (NCT04562766), a randomized phase 3 study. The primary outcome is DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in Regions Except European Union and United Kingdom.

2. Clinical Question

The primary endpoint assessed a sustained pattern of platelet counts rather than a single measurement. A participant had to meet the specified threshold on a sufficient share of scheduled weekly measurements during the final 12 weeks, including qualifying measurements during the final 6 weeks, and had to do so without rescue therapy. The registry also reports adolescent groups, but the principal sponsor comparison described in the registry is between adults receiving rilzabrutinib and adults receiving placebo.

The posted adult results show a durable response in 23.3% of participants receiving rilzabrutinib and 0% receiving placebo. The registry’s sponsor-reported comparison estimates a risk difference of 23.1 percentage points, with a 95% confidence interval from 15.95 to 30.31 and p < 0.001. These are estimates of the observed trial outcome under its recorded definition; they do not by themselves establish how results would vary in other populations or settings.

3. Trial Design

This was a randomized, double-blind, quadruple-masked, parallel-group Phase 3 study comparing oral rilzabrutinib with matching placebo. The registry records enrollment of 232 participants and describes the condition as immune thrombocytopenia. The study included adults and adolescents with persistent or chronic ITP. Its status is completed. The recorded study start is 2020-12-14, and the primary completion date is 2025-01-15.

During the blinded period, the rilzabrutinib arm received 400 mg twice daily for up to 24 weeks; the placebo arm received matching placebo 400 mg twice daily for up to 24 weeks. The brief description says the blinded treatment period lasted 12 to 24 weeks. It describes an open-label period of 28 weeks followed by a 4-week post-dose follow-up. For each participant, the overall study period from screening to the end-of-study visit could last up to 60 weeks. The record also describes a long-term extension with a maximum duration of 12 months from the date of the last adult participant to enter it, and a separate maximum duration of 12 months from the date of the last pediatric participant to enter it.

The primary outcome was defined for the adult and adolescent intent-to-treat population, comprising all randomized participants. The registry presents primary outcome results separately for adults and adolescents. The sponsor-reported primary comparison listed in the record is specifically between adults in the rilzabrutinib and placebo groups. That distinction matters: the adult estimate is not a pooled estimate across age groups.

The record lists 15 outcome measures and 8 analyses. The outcomes include platelet-response measures, rescue therapy, patient-reported fatigue and bleeding assessments, and stability of response. Details of the planned sample-size justification, allocation ratio, stratification factors, and interim analyses 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: 202 adult and 30 adolescent participants were randomized in the study. The study consisted of 3 periods: double-blind (DB) period, open-label (OL) period and safety follow-up or long-term extension (LTE) period. Interim results have been reported up to the database lock (DBL) date of 15-Oct-24 (adult OL period) and 15-Jan-2025 (adolescent DB period).

Only the first 6 of 8 groups are shown.

DB Period (Weeks 1 to 24)

Reasons for not completing this period:

OL Period (From Week 25 to Week 53)

Reasons for not completing this period:

LTE(Weeks 53-183[Adult]&147[Adolescent])

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Adult and adolescent intent-to-treat (ITT) population included all randomized participants.

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: Adult and adolescent randomized population included all participants from screened population who were allocated to a randomized study drug by interactive response technology regardless of whether the study drug was received or not.

6. Primary Endpoint

The registry lists the primary outcome as DB Period: Percentage of Participants With Durable Platelet Response Per Guidance in Regions Except European Union and United Kingdom, measured over Up to 24 weeks.

The primary endpoint was the percentage of participants with durable platelet response, assessed for up to 24 weeks. For the definition used in regions except the European Union and United Kingdom, a response required platelet counts at or above 50,000/mcL for at least two-thirds of at least 8 non-missing weekly scheduled measurements during the final 12 weeks of the 24-week blinded period. It also required at least 2 non-missing weekly scheduled measurements at or above 50,000/mcL during the final 6 weeks. These conditions had to be met in the absence of rescue therapy.

This definition is intended to distinguish a response sustained across repeated assessments from a response at a single visit. Repeated scheduled measurements make the endpoint sensitive to the pattern over time, while the rescue-therapy condition makes clear that qualifying counts achieved with rescue treatment do not satisfy the stated endpoint. General statistical context: defining an endpoint in this way can make it more informative about sustained response, but it also means that missing scheduled measurements and the handling of rescue therapy are important to interpretation.

The registry identifies the primary population as all randomized adults and adolescents, but presents the primary results by age group. In adults, the posted response proportions were 23.3% for rilzabrutinib and 0% for placebo. In adolescents, they were 11.1% and 0%, respectively. The record’s sponsor-reported formal comparison is for adults. The detailed statistical handling of participants who did not meet the required measurement availability is not reported in the registry record.

7. Results Posted in the Registry

• DB Period: Adults: Rilzabrutinib 400 mg BID: 23.3% (31/133) versus 0.0% (0/69) on control; risk difference 23.3 percentage points (95% CI 16.1 to 30.5); unadjusted two-proportion z-test p = <0.001.
• DB Period: Adolescent: Placebo: 0.0% (0/12) versus 0.0% (0/69) on control; risk difference 0.0 percentage points (95% CI 0.0 to 0.0); unadjusted two-proportion z-test p = n/a.
• DB Period: Adolescent: Rilzabrutinib 400 mg BID: 11.1% (2/18) versus 0.0% (0/69) on control; risk difference 11.1 percentage points (95% CI -3.4 to 25.6); unadjusted two-proportion z-test p = 0.005.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

DB Period: Number of Weeks With Platelet Count >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • DB Period: Adults: Rilzabrutinib 400 mg BID: mean 7.50 versus 1.00 on control; difference 6.50 (95% CI 4.93 to 8.07), standardized effect d = 0.90; z-test p = <0.001.
  • DB Period: Adolescent: Placebo: mean 0.80 versus 1.00 on control; difference -0.20 (95% CI -1.21 to 0.81), standardized effect d = -0.10; z-test p = 0.697.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for DB Period: Adults: Rilzabrutinib 400 mg BID than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between DB Period: Adolescent: Placebo and the control. The interval gives the range of effects that remain compatible with the data.

DB Period: Number of Weeks With Platelet Counts >=30,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy

• Endpoint type: Continuous: a mean value per participant, compared as a difference in means.
• Test: Unadjusted two-sample z-test for the difference in means, using the posted standard deviations.
• Result:
  • DB Period: Adults: Rilzabrutinib 400 mg BID: mean 7.30 versus 1.00 on control; difference 6.30 (95% CI 4.75 to 7.85), standardized effect d = 0.88; z-test p = <0.001.
  • DB Period: Adolescent: Placebo: mean 0.60 versus 1.00 on control; difference -0.40 (95% CI -1.17 to 0.37), standardized effect d = -0.21; z-test p = 0.311.
• Interpretation:
  • The 95% confidence interval excludes no difference, so the mean is statistically higher for DB Period: Adults: Rilzabrutinib 400 mg BID than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.
  • The 95% confidence interval includes no difference, so these data do not show a statistically significant difference between DB Period: Adolescent: Placebo and the control. The interval gives the range of effects that remain compatible with the data.

DB Period: Time to First Platelet Count of >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and Doubled From Baseline

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Log Rank); it was not recalculated.
• Result:
  • DB Period: Adults: Placebo vs DB Period: Adults: Rilzabrutinib 400 mg BID: hazard ratio 3.10 (95% CI 1.95–4.93), reported p < 0.001 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically higher for DB Period: Adults: Placebo vs DB Period: Adults: Rilzabrutinib 400 mg BID than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

The secondary outcomes span several related but distinct questions: the number of weeks with platelet counts meeting specified thresholds, time to first qualifying platelet count, rescue-therapy use, fatigue and bleeding assessments, and stability of response during the open-label period. The posted numerical secondary results include longer mean durations meeting platelet-count criteria in the adult rilzabrutinib group than in the adult placebo group. The registry also reports sponsor analyses for those weekly outcomes and for time to first qualifying platelet count. Other listed secondary measures are named in the record, but numerical results for all listed outcomes are not included in the posted results.

In broad terms, the reported adult weekly platelet-count findings point in the same direction as the primary durable-response comparison: the group summaries and sponsor analyses report higher values for the rilzabrutinib group on the specified platelet-count measures. These are related outcomes, not interchangeable repetitions of the primary endpoint. Their definitions differ, and one measures a sustained threshold-based response while others count weeks meeting different criteria or evaluate time to an initial qualifying count.

Secondary findings generally carry less confirmatory weight when many outcomes are tested. Each additional analysis creates further opportunity for chance findings, particularly if the analyses are not adjusted for multiplicity. The registry record does not report a multiplicity adjustment strategy or identify a hierarchy for interpreting secondary endpoints. Therefore, the secondary results can add context and indicate whether patterns are consistent across related measures, but isolated p-values should not be treated as equivalent to the primary test. The registry also does not report the complete numerical results for every listed secondary measure, limiting any attempt to characterize the full pattern across all outcomes.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• DB Period: Number of Weeks With Platelet Count >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy
• DB Period: Number of Weeks With Platelet Counts >=30,000/mcL and at Least Doubled From Baseline in the Absence of Rescue Therapy
• DB Period: Time to First Platelet Count of >=50,000/mcL or Between >=30,000/mcL and <50,000/mcL and Doubled From Baseline
• DB Period: Percentage of Participants Who Required Rescue Therapy
• DB Period: Change From Baseline on Item 10 (Physical Fatigue) of the Immune Thrombocytopenia-Patient Assessment Questionnaire (ITP-PAQ) in Adult Participants at Week 13
• DB Period: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale (IBLS) Assessment in Adult Participants at Week 25 Per Guidance in European Union and United Kingdom
• DB Period: Change From Baseline in Idiopathic Thrombocytopenic Purpura Bleeding Scale Assessment in Adolescent Participants at Week 25 Per Guidance in European Union and United Kingdom
• DB-OL Period: Percentage of Participants With Stability of Response in Adult Participants

9. Statistical Interpretation

10. Statistical Methods Explained

What does the adult risk difference represent?

A risk difference compares the proportion experiencing an outcome in one group with the proportion in another. For this primary endpoint, the outcome is meeting the durable platelet response definition. The posted adult proportions are 23.3% with rilzabrutinib and 0% with placebo. The unadjusted recalculation reports a risk difference of 0.233 and a 95% confidence interval from 0.161 to 0.305. The sponsor’s reported risk difference is 23.1, with a 95% confidence interval from 15.95 to 30.31. These are expressed on different scales in the record; both estimates describe a difference favoring the rilzabrutinib group in the adult comparison.

A confidence interval expresses the uncertainty around an estimated effect under the analysis method. It is not a range that guarantees the true effect lies within its endpoints. General statistical context: an interval that excludes zero for a difference is evidence against a zero difference at the corresponding confidence level, subject to the assumptions of the analysis and the way the endpoint and population were defined. A p-value addresses compatibility with a null hypothesis under an analysis model; it is not the probability that the null hypothesis is true.

Why does the sponsor’s method differ from an unadjusted recalculation?

The sponsor reports a Cochran-Mantel-Haenszel analysis for the adult primary comparison. This method can combine comparisons across strata when the analysis has specified relevant strata. The registry record does not identify the stratification factors in the posted result. The unadjusted recalculation instead compares the posted summary proportions directly, without that adjustment. The estimates are close, but the sponsor analysis is the trial’s reported inferential analysis and should be distinguished from a simple recalculation of summary statistics.

The recalculated adult p-value is < 0.001, while the sponsor-reported p-value is < 0.001. Both are reported as thresholds rather than exact values. Differences in method can produce differences in estimates, intervals, and p-values. Here the registry marks no discrepancy, and the sponsor’s result takes precedence as the study’s own analysis.

How should mean and repeated-measure outcomes be read?

For the secondary outcomes reported as numbers of weeks, the posted group summaries give means and standard deviations. A mean is an average; a standard deviation describes the spread of individual values around that average. The simple recalculations compare the group means. For example, the registry reports a recalculated adult mean difference of 6.5 weeks for the outcome counting weeks meeting the broader platelet-count criteria, with a 95% confidence interval from 4.931 to 8.069 and p < 0.001. The sponsor’s reported analysis for that outcome uses a mixed-effect model with repeated measure and gives an LS mean difference of 6.46, with a 95% confidence interval from 4.923 to 7.990 and p < 0.001.

A repeated-measures model is designed to use information from multiple measurements over time while accounting for the fact that measurements from the same participant are related. The registry also reports an MMRM analysis for another weekly platelet-count outcome. General statistical context: repeated-measures methods can address the structure of longitudinal data, but their validity depends on modeling assumptions and on how missing measurements are handled. The detailed model specification and missing-data assumptions are not reported in the registry record.

What does the time-to-event result estimate?

The time-to-event secondary outcome records time to the first qualifying platelet count. The adult placebo median is not reported as a numerical estimate; the adult rilzabrutinib median is 36.0 days, with a 95% confidence interval from 22.0 to 44.0. The registry’s sponsor analysis uses a log-rank method and reports a hazard ratio of 3.10, with a 95% confidence interval from 1.948 to 4.934 and p < 0.001.

A hazard ratio compares event rates over follow-up under a model or test framework; it is not a ratio of median times. Its interpretation depends on which group is placed in the numerator and on the event coding. The registry labels the comparison as placebo versus rilzabrutinib but does not spell out the coding direction in the displayed result. It is therefore safest to report the value and comparison as recorded rather than infer an unreported direction from the hazard ratio alone. General statistical context: a log-rank comparison uses the timing of events and censoring information, rather than only comparing the proportions with an event at a fixed time.

What are the planning illustrations?

The sample-size illustrations are planning calculations from observed effects, not observed power and not the trial’s own design justification. For the weekly mean outcomes, they give participants per arm for 80% or 90% power under stated assumptions, including two-sided significance level 0.05, equal allocation, and a normal approximation. Rows illustrate planning for 100%, 75%, and 50% of the observed effect. For the time-to-event outcome, the calculation is expressed as total events, using the stated Schoenfeld approach. These illustrations show how required sample size can change when the effect assumed for a future study is smaller than the observed effect. They should not be interpreted as evidence that the present trial had a particular probability of detecting its result.

For the weekly mean outcomes, over-dispersion or substantial variability matters because greater spread makes the group means less precisely estimated. General statistical context: if the outcome distribution is much more variable than a simple model assumes, uncertainty estimates based on that model may be too narrow. The registry posts standard deviations for these outcomes, but does not report a specific over-dispersion assessment.

11. Confidence Intervals and Precision

The adult primary estimate is comparatively more precise than the adolescent estimate in the posted results. The sponsor-reported adult risk difference is 23.1, with a 95% confidence interval from 15.95 to 30.31. The unadjusted recalculation gives 0.233, with an interval from 0.161 to 0.305. Both intervals are separated from zero, although they arise from different analytical approaches and are expressed on different scales in the record.

For adolescents, the recalculated difference is 0.111, with a 95% confidence interval from -0.034 to 0.256. This interval spans zero and covers a range of possible differences, including little or no difference as well as a positive difference. Its width reflects uncertainty; the adolescent groups are much smaller than the adult groups. The posted adolescent proportions therefore warrant cautious interpretation and do not offer the same precision as the adult estimate.

General statistical context: confidence intervals summarize sampling uncertainty under an analysis’s assumptions. They do not account automatically for every source of uncertainty, such as differences between trial participants and patients outside the study, incomplete outcome data, or multiplicity across many endpoints. Nor does a narrow interval guarantee that the endpoint is a complete measure of clinical benefit. The registry’s primary response definition uses repeated platelet measurements and excludes response in the presence of rescue therapy, so the precision estimate applies to that particular outcome definition.

Several secondary results also have intervals. For time to first qualifying platelet count, the adult rilzabrutinib median is 36.0 days, with a 95% confidence interval from 22.0 to 44.0; the placebo median is not reported as a numeric estimate. The sponsor’s hazard ratio interval is from 1.948 to 4.934. These intervals quantify uncertainty for different estimands and should not be directly compared with the risk-difference interval as though they measured the same quantity. The registry does not report confidence intervals for every posted group summary.

12. Analyses Reported by the Sponsor

The sponsor’s primary adult analysis uses the Cochran-Mantel-Haenszel method and reports a risk difference of 23.1, with a 95% confidence interval from 15.95 to 30.31 and p < 0.001. The simple unadjusted recalculation from the posted group summaries gives a risk difference of 0.233, with a 95% confidence interval from 0.161 to 0.305 and p < 0.001. The two estimates are close in their underlying message, but they are not identical analyses: one is the sponsor’s stratified method and the other is an unadjusted re-calculation.

The registry records no discrepancy between the sponsor result and the recalculation. The sponsor’s analysis takes precedence as the trial’s own reported analysis. The recalculation is useful as a transparent check based on the group summaries, not as a replacement for the prespecified or sponsor-conducted analysis. The registry does not report the analysis’s stratification factors or enough detail to reproduce its adjustment independently.

The same distinction applies to secondary outcomes where the sponsor reports model-based estimates. For weekly platelet outcomes, sponsor analyses use a mixed-effect model with repeated measure or MMRM, while simple recalculations compare posted summaries. These methods can yield slightly different estimates and uncertainty because they use different models and may incorporate the repeated measurement structure differently. The sponsor’s reported results should be read as the study analyses, while recalculations remain descriptive checks rather than independent confirmation.

13. Multiplicity, Missing Data and Analysis Populations

The primary population is described as the adult and adolescent intent-to-treat population, including all randomized participants. The registry presents outcomes separately by age group and identifies the sponsor’s formal primary comparison as the adult rilzabrutinib and placebo groups. The record does not report how this age-specific presentation relates to any planned testing hierarchy or whether an overall pooled primary comparison was planned.

The primary endpoint itself requires a minimum quantity of non-missing weekly platelet measurements during specified parts of the blinded period and excludes responses occurring with rescue therapy. This makes measurement availability and rescue treatment central to determining whether a participant meets the endpoint. The registry does not report how participants who lack the required number of measurements were classified, what imputation or other missing-data method was used, or whether sensitivity analyses were conducted. It also does not explain how missingness was handled in the repeated-measure secondary analyses.

The record lists 15 outcome measures and 8 analyses. It does not report whether multiplicity was controlled, whether secondary tests were adjusted, or what testing sequence was planned. Without this information, p-values for secondary outcomes should be regarded as nominal unless the record explicitly identifies an adjustment. A significant nominal p-value does not by itself establish confirmatory evidence when multiple endpoints or analyses are considered.

The registry does identify an intent-to-treat population definition for the primary outcome, but does not provide a fuller account of analysis populations for each secondary measure, exclusions after randomization, or analysis-specific denominators beyond the posted summaries. The handling of protocol deviations, intercurrent events other than rescue therapy, and missing data is not reported in the registry record. These omissions limit assessment of how robust the estimates are to alternative assumptions, and prevent a complete reconstruction of the statistical plan.

14. 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: epistaxis (5.6%), ovarian cyst ruptured (5.6%), thrombocytopenia (2.9%), immune thrombocytopenia (1.4%), conjunctival haemorrhage (1.4%).

During the blinded period, the registry reports serious adverse events in 8 adults receiving placebo and 12 adults receiving rilzabrutinib; among adolescents, the corresponding counts are 0 and 2. It also records 1 death in the adult rilzabrutinib group and no deaths in the other blinded groups. During the open-label period, the registry reports 17 serious adverse events among adults receiving rilzabrutinib and no deaths. These are counts within the recorded groups and periods, not adjusted comparisons of risk.

The record lists serious adverse event terms including epistaxis and ovarian cyst ruptured, each at 5.6%, thrombocytopenia at 2.9%, and immune thrombocytopenia, conjunctival haemorrhage, and haematemesis, each at 1.4%. These listed terms provide context on reported events but do not establish that a treatment caused an event. The registry does not provide a causal assessment in these summary figures.

Safety counts should be interpreted in light of each group’s size and observation period. The open-label group is a different study period from the randomized blinded comparison, and these counts should not be treated as a direct randomized comparison with the placebo group. Serious adverse event counts also do not capture all dimensions of safety, and the summaries do not provide event timing, duration, severity beyond the serious classification, or participant-level detail.

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

The primary result describes the proportion of randomized adults and adolescents meeting a specific sustained platelet-response definition during the blinded period. In adults, the posted response proportion was 23.3% with rilzabrutinib and 0% with placebo. The sponsor’s adult risk-difference estimate was 23.1, with a 95% confidence interval from 15.95 to 30.31 and p < 0.001. This is evidence of a difference between the adult groups on the registry-defined endpoint in this trial.

It does not mean that every participant receiving rilzabrutinib met the response definition: the posted adult proportion is 23.3%. It does not mean that no participant could have had platelet counts that improved without meeting the full durable-response criteria. Nor does the endpoint describe all aspects of ITP, all possible benefits or harms, or outcomes beyond the blinded assessment period. The response definition requires a specified pattern of measurements and no rescue therapy, so the estimate is specific to those rules.

The adolescent result is less precise: the posted response proportions are 11.1% and 0%, and the recalculated risk-difference interval from -0.034 to 0.256 includes zero. The registry does not report a sponsor analysis for the adolescent comparison. These results should not be interpreted as a definitive estimate of the effect in adolescents.

General statistical context: a trial estimate is an estimate for its study population, outcome definition, and follow-up, with uncertainty. It cannot guarantee the same result in another population or under different clinical circumstances. The registry record does not report enough information to assess every design and analysis assumption, including missing-data methods and multiplicity handling. The results are statistical evidence about the recorded outcomes, not individual treatment guidance.

16. Why This Trial Matters Statistically

This trial is statistically informative because it uses randomization and masking to compare rilzabrutinib with placebo during a blinded treatment period. The parallel-group design supports a comparison between groups, while masking can reduce the influence of expectations on outcome assessment and other study processes. The primary endpoint also uses repeated scheduled platelet measurements rather than a single measurement, defining durable response through a prespecified pattern over time.

The endpoint’s structure illustrates a broader issue in clinical-trial analysis: a clinically meaningful question must be translated into an operational outcome rule. Here that rule specifies platelet thresholds, the proportion and timing of measurements required, and the absence of rescue therapy. Those choices shape what the estimate means and how missing measurements affect whether an outcome can be established.

The registry presents both a sponsor-adjusted analysis and summary-based recalculations for selected comparisons. Their close adult primary estimates offer a useful demonstration that an unadjusted check can broadly align with the trial’s reported analysis while remaining methodologically distinct. The adolescent interval also illustrates why point estimates should be read together with precision, especially when group sizes are smaller.

Finally, the mix of primary and secondary outcomes shows why inferential hierarchy matters. Several related outcomes may offer complementary information, but multiple analyses can complicate interpretation if the testing strategy is not reported. Since multiplicity procedures and important missing-data details are not reported in the registry record, conclusions should remain centered on the primary sponsor analysis and appropriately qualified by its endpoint definition and uncertainty.

17. 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.
• Participant counts were reconstructed from posted percentages and arm sizes, so small rounding differences are possible.

Several trial-specific features limit how completely the registry results can be interpreted. The primary endpoint is defined for regions except the European Union and United Kingdom, while the record lists a separate bleeding-scale outcome guided by European Union and United Kingdom guidance. The registry does not explain how the primary endpoint definition relates to participants in those regions or whether any regional analysis was conducted.

The blinded treatment period is described as lasting 12 to 24 weeks, while the primary endpoint definition refers to the final 12 weeks of a 24-week blinded period. The arm descriptions say treatment was given for up to 24 weeks. The record does not clarify the operational handling of participants with shorter blinded treatment exposure for this endpoint. The required number of non-missing measurements and the absence-of-rescue condition are explicit, but the treatment of participants who fail to meet the measurement requirement is not reported.

The adult and adolescent primary results are separated, and the registry’s sponsor-reported comparison covers adults. The adolescent results have wider uncertainty, and no sponsor-reported adolescent primary analysis is listed. The record does not report a prespecified age-group testing plan or a pooled estimate.

Although many secondary outcomes are listed, numerical results are not available in the record for every measure. Multiplicity adjustment, detailed missing-data methods, model specifications beyond the named methods, and the planned sample-size justification are not reported. These omissions restrict assessment of robustness and of the intended inferential hierarchy. Finally, the open-label safety period is not a randomized placebo comparison, so its serious adverse event counts should be interpreted separately from the blinded treatment-period counts.

18. Related Tutorials

19. Related Statistical Calculators

20. Sources

• ClinicalTrials.gov: Study to Evaluate Rilzabrutinib in Adults and Adolescents With Persistent or Chronic Immune Thrombocytopenia (ITP) — NCT04562766.
• Registry record last updated 2026-10-07; status last verified 2026-09.
• Results first posted 2026-02-23.
• 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.

21. Record Summary

The registry describes a completed, randomized, double-blind, quadruple-masked, parallel-group Phase 3 study of rilzabrutinib versus placebo in adults and adolescents with persistent or chronic ITP. Enrollment was 232. Participants received rilzabrutinib or matching placebo 400 mg twice daily during blinded treatment for up to 24 weeks, with an open-label period and follow-up also described.

The primary outcome was durable platelet response during the blinded period, defined using repeated platelet counts and the absence of rescue therapy. In adults, the posted response proportions were 23.3% with rilzabrutinib and 0% with placebo. The sponsor-reported risk difference was 23.1, with a 95% confidence interval from 15.95 to 30.31 and p < 0.001. The adolescent estimate was less precise.

The registry also reports secondary platelet outcomes, time-to-event analysis, and serious adverse event counts. Multiplicity procedures, detailed missing-data methods, and the sample-size justification are not reported in the registry record.