Activity, Safety and Pharmacokinetics in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplant: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Activity, Safety and Pharmacokinetics in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplant (NCT03774082), a na phase 2 study. The primary outcome is Overall Response Rate (ORR) at Cycle 7 Day 1.

2. Clinical Question

3. Trial Design

This was a Phase II, open-label, multicenter, single-group study of ruxolitinib in pediatric participants with moderate or severe cGvHD after allogeneic stem cell transplantation. The official title describes ruxolitinib added to corticosteroids. The brief summary says it was added to the participant’s immunosuppressive regimen. These descriptions place the study treatment in the context of ongoing immunosuppressive care; the registry record does not give a complete account of each participant’s background regimen.

The registry record reports 46 enrolled participants and a completed study. The brief summary states that one participant in the age group from 6 years to under 12 years received study treatment beyond protocol requirements and was excluded from analyses. The safety groups cover 45 participants. The record does not report a complete participant-flow account explaining all analysis populations and exclusions beyond that statement.

Ruxolitinib was given twice a day as a tablet or oral solution, depending on the participant’s group. The safety information identifies groups aged 12 years to under 18 years receiving 10 mg twice a day, aged 6 years to under 12 years receiving 5 mg twice a day, and aged 2 years to under 6 years receiving 4 mg/m2 twice a day. These group descriptions do not establish the number of participants in every eligible age range, nor do they provide a full dosing schedule or treatment-duration account.

With no randomized allocation and no control arm, the design can describe outcomes among treated participants but cannot isolate the effect of ruxolitinib from the course of cGvHD, background treatment, or other influences. Details of the protocol’s sample-size justification, interim analyses, and statistical plan 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: Enrollment initiation into the youngest age group, Group 4, was subject to the availability of data in this age group from study CINC424F12201. However, no participants were enrolled in group 4 (aged ≥ 28 days to \< 2y) due to the completion of the overall study enrolment with participants in the older age groups (groups 1, 2, \& 3).

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS) comprised all subjects to whom study treatment has been assigned and who received at least one dose of study treatment.

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 all subjects to whom study treatment has been assigned and who received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Overall Response Rate (ORR) at Cycle 7 Day 1, measured over At Cycle 7 Day 1 (Day 168); Cycle = 28 Days.

The primary endpoint was overall response rate at Cycle 7 Day 1, corresponding to Day 168, with each cycle defined as 28 days. ORR is a binary participant-level outcome: a participant is counted as having a response if the assessment is a complete response or partial response, subject to the endpoint’s stated restriction on additional systemic therapy for an earlier progression, mixed response, or non-response.

The response assessment used National Institute of Health consensus criteria. The record says scoring was relative to the organ stage at the start of study treatment. This baseline reference matters because response is judged against a participant’s disease status at treatment initiation, rather than by comparing treated participants with a separate group.

In general, a response-rate endpoint gives a compact summary of how many participants meet a prespecified clinical-response definition at a specified assessment time. It does not by itself describe how long a response lasts, all changes in disease manifestations, or outcomes after the assessment. The registry lists duration of response and other outcomes separately, but their results are not reported in the registry record.

The record identifies a 90% confidence interval as the endpoint’s dispersion measure, but it does not report the ORR estimate or its interval. Therefore, the observed response rate and the precision of that estimate cannot be described from this registry entry.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the endpoint estimate?

In general, a binary response endpoint classifies each participant according to whether a defined event or status occurred. For ORR, the relevant status is whether the participant meets the complete-response or partial-response definition at the specified assessment, while also satisfying the stated condition concerning additional systemic therapy. A response proportion summarizes the share of the analysis population meeting that definition. The registry record does not report the observed count or proportion for this trial, so no estimate can be interpreted.

The endpoint is time-specific: the primary assessment was scheduled for Cycle 7 Day 1, identified as Day 168. An endpoint at a set visit answers a different question from a best-response measure, which can use assessments across a period, or a duration-of-response measure, which concerns persistence after response. The registry lists these as separate outcomes. Their definitions and results, beyond the names shown, are not reported in the registry record.

What would a confidence interval convey?

In general, a confidence interval expresses uncertainty around an estimate under the statistical method used to construct it. For a response proportion, the interval would show a range of values compatible with the observed data and the selected interval procedure. A narrower interval generally indicates greater precision under that procedure, while a wider interval indicates more uncertainty. An interval is not a guarantee that the true value lies within its particular bounds, and it does not account automatically for biases in design, measurement, or missing data.

The endpoint lists a 90% confidence interval, but neither its bounds nor the point estimate is reported in the registry record. The interval method is also not reported. It is therefore not possible to evaluate precision, compare an estimate with a benchmark, or assess whether the interval was calculated using an appropriate method for the trial’s data.

Why does the single-group design matter?

In general, random allocation to treatment groups can help balance measured and unmeasured prognostic factors between groups. A single-group study has no concurrent control group, so an observed outcome cannot distinguish the treatment’s contribution from the natural course of disease, background therapies, participant selection, or other influences. This is a design limitation, not a statistical adjustment that can be resolved by presenting a confidence interval around the single-group response rate.

This study was open-label and single-group, with allocation listed as not applicable. The registry does not report a comparative treatment estimate, and it would be incorrect to describe the ORR as a relative benefit or difference versus a control. The study can still provide descriptive information about outcomes and safety in the enrolled participants, subject to the limitations of the reported data.

How should the analysis population be understood?

In general, an analysis population defines which participants contribute to an endpoint estimate. The registry defines the Full Analysis Set as subjects to whom study treatment was assigned and who received at least one dose. The brief summary separately notes that one enrolled participant was excluded from analyses after receiving treatment beyond protocol requirements. The record does not report the primary endpoint’s participant denominator or a detailed flow from enrollment to each endpoint analysis. Thus, the analysis-set definition alone does not reveal how many participants had an evaluable Cycle 7 assessment.

Missing outcome data can affect a response-rate estimate because the result may depend on whether participants without an assessment are excluded, counted as nonresponders, or handled by another prespecified method. In general, these choices can change both the estimate and its uncertainty. The registry record does not report the missing-data approach, the number of missing primary assessments, or sensitivity analyses. No particular handling rule should be assumed.

What can be said about statistical testing?

The primary outcome is described as a percentage with a confidence interval, but the registry record does not report a hypothesis test, a benchmark response rate, or a treatment-effect contrast. It also does not report the detailed statistical analysis plan. A confidence interval around a single-group estimate would quantify sampling uncertainty under its method; by itself, it would not establish a causal treatment effect.

In general, over-dispersion is relevant when observed variation is greater than a statistical model expects. For a simple binary endpoint, the chosen interval procedure and its assumptions matter, particularly with a limited analysis population or sparse outcomes. The trial-specific method for assessing or addressing such issues is not reported in the registry record. No recalculated estimate is available to compare with a sponsor analysis.

The record lists 12 outcome measures and no posted analyses. The existence of multiple outcomes raises a general question about multiplicity: when many hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan addresses it. However, the registry does not report enough information to determine which outcomes were tested, whether testing was planned, or whether any multiplicity adjustment was used. These are unknowns, not evidence that an adjustment was or was not made.

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("≥ 12y - < 18y RUX 10mg BID (Group 1)", "≥ 6y - < 12y RUX 5mg BID (Group 2)", "≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)")
n      <- c(22, 16, 7)
events <- c(8, 8, 2)
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  ≥ 12y - < 18y RUX 10mg BID (Group 1)  22  8  36.4  17.2  59.3  19.7  57.0  19.7  57.3
ARM  ≥ 6y - < 12y RUX 5mg BID (Group 2)  16  8  50.0  24.7  75.3  28.0  72.0  27.8  72.2
ARM  ≥ 2y - < 6y RUX 4mg/m2 BID (Group 3)  7  2  28.6  3.7  71.0  8.2  64.1  8.5  65.1

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the primary ORR assessment at Cycle 7 Day 1 and a set of secondary outcomes. These include ruxolitinib concentrations by timepoint, duration of response, ORR at Cycle 4 Day 1, best overall response, failure-free survival, cumulative incidence of malignancy relapse or recurrence, non-relapse mortality, and overall survival. The record reports 12 outcome measures in total, but detailed results and analyses are not posted for these outcomes.

In general, when a study evaluates multiple outcomes or performs repeated hypothesis tests, multiplicity can make chance findings more likely across the full set of tests. Prespecified ordering, adjustment procedures, or a distinction between confirmatory and exploratory outcomes can help readers understand how results should be interpreted. The registry record does not report the statistical plan, whether multiplicity was addressed, or whether the secondary outcomes were treated as confirmatory or exploratory. No conclusion about the sponsor’s approach is warranted from the information posted.

The primary endpoint’s numerical result and confidence interval are not reported. The record also does not report the number of missing Cycle 7 assessments, the handling of missing endpoint data, or sensitivity analyses. In general, missing-data assumptions matter because excluding participants without an assessment can yield a different response estimate from treating missing outcomes as nonresponse or using another method. Which approach was used in this study is not reported in the registry record.

The Full Analysis Set definition and the note about one participant excluded after treatment beyond protocol requirements provide some population information, but they do not establish the primary endpoint denominator or explain the disposition of every enrolled participant. The safety results refer to 45 participants. The registry record does not say whether all those participants contributed to every efficacy outcome.

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: febrile neutropenia (14.3%), pyrexia (14.3%), aspergillus infection (14.3%), human bocavirus infection (14.3%), parainfluenzae virus infection (14.3%).

The safety information separates on-treatment and post-treatment periods and reports counts by age group, as well as an all-participants group. In the on-treatment all-participants group, 26 of 45 were recorded in the serious adverse-event count, and 44 of 45 were recorded in the other adverse-event category. In the post-treatment all-participants group, the corresponding counts were 3 of 45 and 6 of 45. These are the registry’s event-group figures; they do not provide a randomized comparison.

The age-specific on-treatment serious adverse-event counts were 15 of 22 for ages 12 years to under 18 years, 7 of 16 for ages 6 years to under 12 years, and 4 of 7 for ages 2 years to under 6 years. The post-treatment serious adverse-event counts were 3 of 22, 0 of 16, and 0 of 7, respectively. The registry also lists deaths by period and age group: 3 in the on-treatment all-participants group and 8 in the post-treatment all-participants group. These entries do not establish cause or attribution.

The listed serious adverse-event terms each have a reported value of 14.3%: febrile neutropenia, pyrexia, Aspergillus infection, human bocavirus infection, parainfluenzae virus infection, and viral pneumonia. The record does not explain the denominator or calculation basis for these term-specific percentages. Counts and classifications should therefore be read as registry descriptions, not as evidence that treatment caused the events.

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

The study addresses a clinically focused question: what response and safety outcomes were recorded when ruxolitinib was added to immunosuppressive treatment for pediatric participants with moderate or severe cGvHD after allogeneic stem cell transplantation? Its Phase II, open-label, single-arm design can describe outcomes among participants who received study treatment. The safety groups and the endpoint definition give readers some context for what was measured.

However, the primary ORR estimate and its stated 90% confidence interval are not reported in the registry record. That omission prevents readers from knowing the observed response proportion or its statistical precision from this entry. Results for the listed secondary outcomes are also not reported. The treatment description and endpoint definition cannot substitute for outcome data.

Even with a reported response proportion, a single-arm result would not show how the outcome compares with a control group. Differences in disease course, background immunosuppression, participant characteristics, and other factors could contribute to observed outcomes. The open-label design is another feature to consider when interpreting assessments, though the record does not report enough detail to quantify any influence.

The safety figures are counts in the registry’s stated treatment-period groups. They can describe how many participants were recorded in each category, but without a comparator they do not establish excess risk attributable to ruxolitinib. The listed deaths are not accompanied by cause or attribution details in the information, and the serious-event term percentages lack a stated denominator in the record.

Accordingly, the registry entry documents a pediatric treatment study and the outcomes it set out to assess, but it does not provide the numerical efficacy results needed to characterize the primary response finding. It also does not provide the analytic detail needed to evaluate missing data, multiplicity, or the full statistical plan. Those absences limit what can be concluded from the posted record; they are not evidence for a particular clinical outcome.

14. Why This Trial Matters Statistically

This trial is statistically notable for the gap between a clearly defined primary question and the outcome information posted in the registry record. The primary endpoint specifies a response definition, a scheduled assessment, a reference to baseline organ stage, and a confidence-interval measure. Yet the numerical response estimate and interval are not reported. A precise endpoint definition supports interpretation only when accompanied by the result and enough analysis detail to understand its denominator.

The single-group design is also important for clinical researchers reading response outcomes. A response rate in treated participants is descriptive; it does not estimate a randomized contrast. This distinction prevents a common interpretive error: treating a within-group outcome as if it measured what would have happened under a different treatment. The design can inform descriptions of observed participants, but causal comparisons require a different evidentiary structure.

The registry also illustrates why analysis populations and missing-data rules matter. It identifies a Full Analysis Set and notes an exclusion after treatment beyond protocol requirements, but it does not report the primary endpoint denominator or missing-assessment handling. Without those details, readers cannot fully trace the path from enrollment to the endpoint estimate, even if that estimate were present.

Finally, the multiple listed outcomes raise questions about how results were selected and interpreted. In general, a prespecified analysis plan and transparent reporting of all planned outcomes help readers distinguish primary evidence from exploratory findings. The statistical plan and outcome results are not reported in the registry record. The value of this entry is therefore principally in documenting the design, endpoint framework, and safety categories rather than supporting an estimate of treatment effect.

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 of the posted record is that the primary ORR result and its confidence interval are not reported. Without the point estimate, interval bounds, and endpoint denominator, readers cannot assess the observed response frequency or its precision. The registry also does not report results for the listed secondary outcomes, including response at Cycle 4 Day 1, best overall response, duration of response, failure-free survival, relapse or recurrence, non-relapse mortality, overall survival, and pharmacokinetic outcomes.

The design was open-label and single-group, with no control arm. As a result, observed outcomes cannot be compared directly with a concurrent control or attributed solely to ruxolitinib. The registry does not report a detailed account of background immunosuppressive treatment, response-assessment procedures beyond the stated criteria, or measures used to limit assessment bias.

The brief summary reports 46 enrolled participants and identifies one participant excluded from analyses after treatment beyond protocol requirements. Safety groups cover 45 participants, but the record does not give a complete participant flow for each outcome. The primary endpoint denominator, number of missing assessments, and missing-data method are not reported. These omissions limit assessment of how exclusions or incomplete follow-up may have affected the endpoint.

The statistical plan, sample-size justification, interim-analysis approach, and handling of multiplicity are not reported in the registry record. The record also does not state the method used to calculate the primary confidence interval. Safety-term percentages are listed without a stated denominator, and the death entries do not include attribution details in the information described.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Activity, Safety and Pharmacokinetics in Pediatric Subjects With Moderate and Severe Chronic Graft vs. Host Disease After Allogeneic Stem Cell Transplant — NCT03774082.
• Registry record last updated 2025-12-11; status last verified 2025-11.
• Results first posted 2025-04-17.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

19. Record Summary

NCT03774082 is a completed Phase II, open-label, multicenter, single-group study sponsored by Novartis Pharmaceuticals. The study start date was 2020-05-20, and primary completion was 2022-02-25. It enrolled 46 pediatric participants with moderate or severe cGvHD after allogeneic stem cell transplantation.

Participants received ruxolitinib twice a day as a tablet or oral solution, in addition to immunosuppressive treatment. The primary endpoint was ORR at Cycle 7 Day 1, defined as Day 168, with a 90% confidence interval specified. One participant was excluded from analyses after receiving treatment beyond protocol requirements.

The registry record does not report the primary endpoint estimate or its confidence interval, and it does not report results for the listed secondary outcomes. Safety counts are reported for 45 participants across treatment periods and age groups. The detailed statistical plan, missing-data handling, and multiplicity approach are not reported in the registry record.