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 Study of Pharmacokinetics, Activity and Safety of Ruxolitinib in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease (NCT03491215), a na phase 1, phase 2 study. The primary outcome is Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03491215 |
| Phase | Phase 1, Phase 2 |
| Condition | Acute Graft Versus Host Disease |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 45 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis Pharmaceuticals |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned infants, children, and adolescents from 28 days of age to younger than 18 years with grade II-IV acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The brief summary includes patients with steroid-refractory acute graft-versus-host disease as well as patients with acute graft-versus-host disease. Four age groups were planned, from adolescents aged 12 to younger than 18 years through infants aged 28 days to younger than 2 years.
Intervention
Participants received ruxolitinib added to their immunosuppressive regimen, including corticosteroids. The regimen was planned for 24 weeks, with dosing twice a day. Tablet, capsule, or oral solution was used depending on the participant group. The study was open-label, so treatment assignment was not masked.
Comparator
There was no separate control group. The registry classifies the study as single-group, with allocation not applicable. Consequently, the study does not provide a randomized, like-for-like comparison of ruxolitinib plus background treatment against a control treatment. Changes during follow-up cannot by themselves distinguish treatment effects from other influences.
Primary question
The primary Phase I question was pharmacokinetic: what was the area under the concentration-time curve from time zero to the last measurable concentration, or AUClast, in participants with acute or steroid-refractory acute graft-versus-host disease? The registry specifies a geometric mean as the summary measure and a geometric coefficient of variation for dispersion. Numerical AUClast results are not reported in the registry record, so the primary pharmacokinetic estimate cannot be described from that record.
3. Trial Design
This was a Phase I/II, open-label, multicenter, single-arm study of ruxolitinib added to corticosteroids and the participant's immunosuppressive regimen. The registry lists an enrollment of 45 and a completed status. The listed start date is 2019-02-21, and the primary completion date is 2021-03-11. The sponsor was Novartis Pharmaceuticals.
The planned population was pediatric patients aged at least 28 days and younger than 18 years with grade II-IV acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation. The summary also describes grade II-IV steroid-refractory acute graft-versus-host disease. The design divided participants into four age groups: 12 to younger than 18 years, 6 to younger than 12 years, 2 to younger than 6 years, and 28 days to younger than 2 years.
Ruxolitinib was given twice a day for a planned duration of 24 weeks, in tablet, capsule, or oral-solution form according to group. The registry lists no masking and no allocation to a comparator arm. Although the design included four planned age groups, the reported on-treatment safety groups with participants at risk cover the first three age ranges; the group-four safety row lists zero participants at risk. Whether any younger participants were enrolled is not reported in the registry record.
The primary endpoint was a pharmacokinetic measure, not a clinical response measure. The listed secondary outcomes include response rates, pharmacokinetic relationships with response and safety, duration of response, and cumulative steroid dose. The registry lists 33 outcome measures and 15 analyses. The protocol's sample-size justification, detailed statistical plan, and any interim-analysis 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: Five subjects were to be enrolled to each age group with no minimum for Group 4, although no subjects were enrolled in Group 4. All subjects participating in Phase I also participated in Phase II so the number of subjects in each phase is identical. The study was conducted in 8 countries and 19 centers.
Overall Study
| Stage | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| STARTED | 18 | 12 | 15 | 0 |
| Rux Formulation - Received Tablet | 18 | 10 | 0 | 0 |
| Rux Formulation - Received Capsule | 0 | 2 | 7 | 0 |
| Rux Formulation - Received Oral Solution | 0 | 0 | 8 | 0 |
| COMPLETED | 11 | 10 | 14 | 0 |
| NOT COMPLETED | 7 | 2 | 1 | 0 |
Reasons for not completing this period:
| Reason | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y |
|---|---|---|---|---|
| Death | 6 | 2 | 1 | 0 |
| Physician Decision | 1 | 0 | 0 | 0 |
Analysis population for the primary outcome, as defined in the registry: PAS: The Pharmacokinetic Analysis Set (PAS) included all subjects who provided at least one evaluable PK concentration. For a concentration to be evaluable, subjects were required to: * Take the dose of ruxolitinib prior to PK sample. * For pre-dose samples, to not vomit within 2 hours after the previous dosing of ruxolitinib prior to sampling; for post-dose samples, to not vomit within 2 hours after the dosing of ruxolitinib. No subjects were enrolled in Group 4.
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) comprised all subjects to whom study treatment was assigned and who received at least one dose of study treatment. No subjects were enrolled in Group 4.
| Characteristic | Unit | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg BID | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg BID | Group 3: Subjects ≥ 2y to < 6y - RUX 4mg/m^2 BID | Group 4: Subjects >= 28 Days to < 2y | Total |
|---|---|---|---|---|---|---|
| Participants analysed | 18 | 12 | 15 | 0 | 45 | |
| Age, Continuous | Months | 172.7 (SD 18.94) | 86.1 (SD 11.08) | 45.5 (SD 14.57) | — | 107.2 (SD 58.43) |
| Sex: Female, Male: Female | Participants | 5 | 7 | 5 | 0 | 17 |
| Sex: Female, Male: Male | Participants | 13 | 5 | 10 | 0 | 28 |
| Race/Ethnicity, Customized: White | Participants | 11 | 5 | 4 | — | 20 |
| Race/Ethnicity, Customized: Asian | Participants | 3 | 3 | 5 | — | 11 |
| Race/Ethnicity, Customized: Missing -Note: race is not collected in France | Participants | 4 | 4 | 6 | — | 14 |
6. Primary Endpoint
The registry lists the primary outcome as Phase I: Measurement of Pharmacokinetic (PK) Parameter, AUClast, in aGvHD and SR-aGvHD Patients, measured over Day 1: at predose, 0.5,1,1.5, 2, 4, 6, 9 hours post dose.
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | ng*hr/mL |
| Endpoint classification | not reduced to a single comparison |
The primary Phase I endpoint was AUClast, the area under the concentration-time curve from time zero to the last measurable concentration sampling time, Tlast. It summarizes drug exposure across the observed concentration-time profile, rather than measuring a clinical response directly. Pharmacokinetic exposure measures help characterize how much drug is present over time and can inform the description of dosing across age groups.
The registry specifies that AUClast was summarized using a geometric mean, with a geometric coefficient of variation describing dispersion. A geometric mean is a useful summary for positive measurements that vary multiplicatively or have a right-skewed distribution. The geometric coefficient of variation describes relative variation on a multiplicative scale; it is not the same as a standard deviation on the original scale.
Sampling was scheduled on Day 1 at predose and at 0.5, 1, 1.5, 2, 4, 6, and 9 hours after dosing. The description says Groups 1-3 had extensive pharmacokinetic sampling and Group 4 had sparse sampling. Sparse sampling can reduce the amount of blood collection required, but individual concentration-time profiles are less densely observed. The actual AUClast estimates, group-specific results, and uncertainty measures are not reported in the registry record.
Because AUClast is a pharmacokinetic endpoint, its value alone does not establish whether participants experienced clinical response or how ruxolitinib compares with another treatment. Those are distinct questions addressed, if reported, through clinical outcomes and comparative designs.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry identifies pharmacokinetic exposure as the primary Phase I endpoint. It defines AUClast and specifies a geometric-mean summary with geometric coefficient of variation, but does not report the numerical estimate, its dispersion, or the number of participants contributing to the primary analysis. Accordingly, the magnitude and precision of the primary pharmacokinetic result cannot be interpreted from the registry record.
The study's single-arm design is central to reading any clinical outcome. Participants received ruxolitinib alongside their existing immunosuppressive treatment, with no separate control arm. Any response or change observed during follow-up would describe outcomes in this treated group; without a concurrent comparator, it would not isolate the contribution of ruxolitinib from background treatment, disease course, supportive care, or other influences. A randomized comparison is not reported.
The registry lists several secondary clinical and pharmacokinetic outcomes, including complete or partial response, response at Day 14, exposure relationships with overall response at Day 28 and durable response at Day 56, duration of response, weekly cumulative steroid dose through Day 56, and exposure relationships with bleeding and infection. The names of these outcomes do not establish their results. Their numerical estimates and precision are not reported in the registry record.
The safety information does include reported counts. During on-treatment follow-up, serious adverse events affected 24 of 45 participants across the all-subjects group, and other adverse events affected 45 of 45. The registry lists zero on-treatment deaths in each of the three age-specific groups with participants at risk. Separate post-treatment survival follow-up rows list deaths for the first three age groups. These counts describe events recorded in the study; they do not provide a comparison with an untreated or differently treated group.
For serious adverse-event terms, the registry lists pyrexia at 13.3%, septic shock at 11.1%, acute kidney injury at 11.1%, febrile neutropenia at 8.3%, pericardial effusion at 8.3%, and intestinal perforation at 8.3%. These percentages should be read as registry-reported figures, not as evidence of comparative risk. The record excerpt does not give the term-specific counts or explain the denominator used for each percentage.
Overall, the posted information supports a description of the study design, endpoint definition, and selected safety counts. It does not support a conclusion about the size or precision of the primary pharmacokinetic result, nor a causal estimate of treatment benefit or harm versus a comparator.
9. Statistical Methods Explained
The main statistical feature of the primary endpoint is its focus on exposure. AUClast integrates measured drug concentrations over the observed time interval, from time zero through the last measurable sample. It is therefore a summary of a concentration-time profile. It does not directly measure symptom improvement, response, or survival. The registry defines AUClast in these terms and identifies it as the primary Phase I measure.
Why use a geometric mean?
General statistical explanation: measurements such as drug exposure are positive, and their variability can be proportional rather than additive. For example, a change by a multiplicative factor can be more meaningful than a fixed absolute change across all participants. In such settings, analysts often transform values to a logarithmic scale, calculate a mean there, and transform the summary back. The resulting geometric mean represents a central value on the original scale while respecting multiplicative variation.
The registry names the geometric mean as the parameter for AUClast. It does not report the actual geometric mean or a confidence interval. A confidence interval, in general, expresses the range of values compatible with the data and the analysis under its assumptions. Without the estimate and interval, readers cannot assess how precisely the exposure was estimated.
What does geometric coefficient of variation describe?
General statistical explanation: the geometric coefficient of variation summarizes relative spread for measurements analyzed on a multiplicative scale. A larger value indicates greater relative variation among measurements; it should not be read as a standard deviation in the original measurement units. The registry specifies this measure of dispersion but does not report its value. The causes of any variation, such as differences between participants or age groups, cannot be assessed from the endpoint description alone.
How does the sampling schedule matter?
The registry describes Day 1 sampling at predose and at 0.5, 1, 1.5, 2, 4, 6, and 9 hours after dosing. It states that Groups 1-3 used extensive sampling and Group 4 used sparse sampling. General statistical explanation: an area-under-the-curve estimate depends on the concentration measurements available over time and on the method used to represent the curve between observations. Dense sampling can characterize the observed profile more directly, while sparse sampling involves fewer observed time points and requires appropriate analysis to estimate exposure. The specific estimation method and its assumptions are not reported in the registry record.
The registry describes a Pharmacokinetic Analysis Set as including subjects who provided at least one evaluable pharmacokinetic concentration. It states that an evaluable concentration required the participant to take ruxolitinib before the sample; it also begins a condition for predose samples concerning vomiting within 2 hours after dosing. The available description is incomplete, so the full criteria for evaluability and the number of participants in this analysis set are not reported in the registry record.
What can the single-arm structure estimate?
General statistical explanation: a single-arm study can describe outcomes and measurements in the participants who received the study regimen. It does not directly estimate a between-group treatment contrast because there is no concurrent comparator group. Differences from a historical or expected outcome would depend on assumptions about comparability, and such a comparison is not described in the registry record. The design is open-label, so treatment knowledge could also influence outcome assessment or participant reporting for outcomes that involve judgment or subjective experience. Whether response assessment was blinded is not reported in the registry record.
The registry lists 33 outcome measures and 15 analyses, including pharmacokinetic and clinical measures. A list of outcome measures does not by itself specify the statistical model, adjustment variables, handling of repeated measures, or inferential testing strategy. Those details are not reported in the registry record. Likewise, the record does not report a statistical plan for estimating precision or comparing age groups.
How should planning illustrations be understood?
General statistical explanation: a sample-size calculation asks how many observations a hypothetical design might require under stated assumptions about the effect to detect, variability, significance level, allocation, and analysis. The planning illustration associated with the posted results uses a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. It describes effects as fractions of the observed effect; time-to-event illustrations use a total event count, while other illustrations use participants per arm.
Those assumptions describe a hypothetical planning exercise, not this trial's design. This study was single-arm, and the illustration's equal allocation between two arms is not a description of observed enrollment. The illustrated sample sizes are planning scenarios, not observed power and not evidence that the completed study had a particular probability of detecting an effect. The study's own sample-size justification is not reported in the registry record.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 33 outcome measures and 15 analyses. Multiple outcomes and analyses create a multiplicity question: if many hypotheses are tested, the chance of at least one apparently positive finding can increase when each is assessed without adjustment. General statistical explanation: prespecified priorities and an explicit multiplicity strategy help readers distinguish confirmatory findings from exploratory ones. The registry record does not report whether multiplicity adjustments were planned or used, how the secondary outcomes were prioritized, or which analyses were intended as confirmatory.
The primary endpoint is pharmacokinetic, while listed secondary outcomes span response, steroid exposure, duration of response, and safety relationships with AUClast. The registry names these measures but does not report their numerical results, analysis models, or uncertainty estimates. It is therefore not possible to determine from the registry record how many participants contributed to each secondary outcome or whether all listed analyses were completed as planned.
Missing-data handling is also not reported in the registry record. The available Pharmacokinetic Analysis Set description requires at least one evaluable concentration and gives partial criteria for evaluability, but the complete criteria are not available in the record description. The number of participants excluded from pharmacokinetic analyses, reasons for missing samples, and any imputation or sensitivity analysis are not reported in the registry record.
The registry does not state how missing clinical response assessments, incomplete follow-up, treatment discontinuation, or missing steroid-dose measurements were handled. It also does not report whether analyses used all enrolled participants or outcome-specific analysis populations, apart from the partial definition of the Pharmacokinetic Analysis Set. These gaps limit assessment of whether the analyzed participants represented the full enrolled group and how missing observations might affect the findings.
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 |
|---|---|---|---|
| Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | 11 | 18 | 61.1% |
| Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | 7 | 12 | 58.3% |
| Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | 6 | 15 | 40.0% |
| All Subjects | 24 | 45 | 53.3% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | 0 of 18 |
| Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | 0 of 12 |
| Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | 0 of 15 |
| All Subjects | 0 of 45 |
| Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | 6 of 18 |
| Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) | 2 of 12 |
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 |
|---|---|
| Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | 18 of 18 |
| Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | 12 of 12 |
| Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | 15 of 15 |
| All Subjects | 45 of 45 |
| Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | 0 of 0 |
| Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) | 0 of 0 |
Most frequent serious adverse event terms
| Event term | Organ system | Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | All Subjects | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) |
|---|---|---|---|---|---|---|---|
| Pyrexia | General disorders | 1 of 18 | 1 of 12 | 2 of 15 | 4 of 45 | n/a of 0 | n/a of 0 |
| Febrile neutropenia | Blood and lymphatic system disorders | 1 of 18 | 1 of 12 | 0 of 15 | 2 of 45 | n/a of 0 | n/a of 0 |
| Sepsis | Infections and infestations | 0 of 18 | 1 of 12 | 1 of 15 | 2 of 45 | n/a of 0 | n/a of 0 |
| Septic shock | Infections and infestations | 2 of 18 | 0 of 12 | 0 of 15 | 2 of 45 | n/a of 0 | n/a of 0 |
| Viral haemorrhagic cystitis | Infections and infestations | 1 of 18 | 0 of 12 | 1 of 15 | 2 of 45 | n/a of 0 | n/a of 0 |
| Acute kidney injury | Renal and urinary disorders | 2 of 18 | 0 of 12 | 0 of 15 | 2 of 45 | n/a of 0 | n/a of 0 |
| Haemorrhagic disorder | Blood and lymphatic system disorders | 1 of 18 | 0 of 12 | 0 of 15 | 1 of 45 | n/a of 0 | n/a of 0 |
| Immune thrombocytopenia | Blood and lymphatic system disorders | 1 of 18 | 0 of 12 | 0 of 15 | 1 of 45 | n/a of 0 | n/a of 0 |
| Neutropenia | Blood and lymphatic system disorders | 1 of 18 | 0 of 12 | 0 of 15 | 1 of 45 | n/a of 0 | n/a of 0 |
| Thrombocytopenia | Blood and lymphatic system disorders | 1 of 18 | 0 of 12 | 0 of 15 | 1 of 45 | n/a of 0 | n/a of 0 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Group 1: Subjects >=12y - <18y - RUX 10mg (On-treatment) | Group 2: Subjects >=6y - <12y - RUX 5mg (On-treatment) | Group 3: Subjects >=2y - <6y - RUX 4mg/m2 (On-treatment) | All Subjects | Group 1: Subjects ≥ 12y to < 18y - RUX 10mg (Post-treatment Survival Follow-up) | Group 2: Subjects ≥ 6y to < 12y - RUX 5mg (Post-treatment Survival Follow-up) |
|---|---|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | 6 of 18 | 5 of 12 | 9 of 15 | 20 of 45 | n/a of 0 | n/a of 0 |
| Neutrophil count decreased | Investigations | 5 of 18 | 2 of 12 | 5 of 15 | 12 of 45 | n/a of 0 | n/a of 0 |
| Neutropenia | Blood and lymphatic system disorders | 6 of 18 | 2 of 12 | 1 of 15 | 9 of 45 | n/a of 0 | n/a of 0 |
| Alanine aminotransferase increased | Investigations | 5 of 18 | 2 of 12 | 2 of 15 | 9 of 45 | n/a of 0 | n/a of 0 |
| Hypertension | Vascular disorders | 2 of 18 | 2 of 12 | 5 of 15 | 9 of 45 | n/a of 0 | n/a of 0 |
| Thrombocytopenia | Blood and lymphatic system disorders | 6 of 18 | 0 of 12 | 2 of 15 | 8 of 45 | n/a of 0 | n/a of 0 |
| Platelet count decreased | Investigations | 0 of 18 | 2 of 12 | 6 of 15 | 8 of 45 | n/a of 0 | n/a of 0 |
| White blood cell count decreased | Investigations | 0 of 18 | 2 of 12 | 5 of 15 | 7 of 45 | n/a of 0 | n/a of 0 |
| Hypokalaemia | Metabolism and nutrition disorders | 4 of 18 | 3 of 12 | 0 of 15 | 7 of 45 | n/a of 0 | n/a of 0 |
| Pyrexia | General disorders | 2 of 18 | 2 of 12 | 2 of 15 | 6 of 45 | n/a of 0 | n/a of 0 |
Serious events with the highest arm-level rate: pyrexia (13.3%), septic shock (11.1%), acute kidney injury (11.1%), febrile neutropenia (8.3%), pericardial effusion (8.3%).
The registry reports on-treatment adverse-event counts for three age-specific groups and an all-subjects group. In the all-subjects group, serious adverse events affected 24 of 45 participants, while other adverse events affected 45 of 45. The listed on-treatment death count is zero for each age-specific group with participants at risk. The registry also gives separate post-treatment survival follow-up rows, with deaths listed for the first three age groups; those counts are follow-up records and should not be combined with the on-treatment rows.
The listed serious adverse-event terms and percentages are pyrexia, 13.3%; septic shock, 11.1%; acute kidney injury, 11.1%; febrile neutropenia, 8.3%; pericardial effusion, 8.3%; and intestinal perforation, 8.3%. These are registry-reported percentages. The term-specific counts and percentage denominators are not reported in the registry record, so the figures cannot be independently interpreted as counts or compared across groups from this information alone.
General statistical explanation: adverse-event counts describe events recorded during a defined observation period and in a defined population. In an uncontrolled study, they do not establish whether an event was caused by treatment or whether its frequency differs from another treatment. Follow-up duration and exposure can also affect opportunities to observe events; detailed event-specific exposure and follow-up data are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The study addresses pharmacokinetics, activity, and safety of ruxolitinib added to immunosuppressive treatment in pediatric patients with acute graft-versus-host disease. Its primary Phase I endpoint is AUClast, a measure of drug exposure through the last measurable concentration. The registry defines the measure and its planned summary statistics, but does not report the numerical AUClast result. The primary endpoint's magnitude and precision therefore cannot be assessed from the registry record.
The safety information offers a descriptive account of events recorded during treatment and post-treatment survival follow-up. Serious adverse events affected 24 of 45 participants in the all-subjects on-treatment group, and other adverse events affected 45 of 45. The reported serious-event terms and percentages provide additional descriptions, but the registry does not give the term-specific counts or denominators in the information available. Such figures do not, on their own, identify causes or establish comparative risks.
The study had no control group. It can describe measurements and events among participants who received the regimen, but it cannot directly show how those outcomes compare with outcomes under another regimen. The registry also lists clinical response and other secondary outcomes, but their numerical results are not reported in the registry record. The outcome names alone are not evidence of response or of a treatment effect.
General statistical explanation: a treatment effect is a contrast between outcomes under different treatment conditions. A single-arm study observes one treatment condition, so causal interpretation requires assumptions that cannot be checked through a concurrent randomized comparison within the study. The findings should therefore be understood as descriptive evidence from the enrolled group, rather than as a controlled estimate of the effect of adding ruxolitinib.
The study does not establish that its results apply equally across all pediatric ages. Although four age groups were planned, the on-treatment safety rows with participants at risk cover three age ranges, and the group-four row lists zero at risk. Whether younger participants were enrolled and how their data were analyzed are not reported in the registry record.
13. Why This Trial Matters Statistically
This study illustrates how a clinical trial can have a primary endpoint that is not a clinical response. AUClast describes pharmacokinetic exposure, while response, safety, and steroid-use outcomes address different questions. Keeping those endpoint types distinct matters: an exposure estimate characterizes drug levels over time, but it does not by itself establish clinical benefit or harm.
The age-spanning design also raises a practical statistical issue. The planned groups ranged from adolescents to infants, and the registry describes extensive sampling in Groups 1-3 but sparse sampling in Group 4. General statistical explanation: sampling strategies can differ when feasibility and participant burden differ, but estimates from differing schedules depend on appropriate methods and should be interpreted with their uncertainty. The registry does not report group-specific exposure estimates or the method used to derive them.
The single-arm structure is equally important. A study may describe what was observed among treated participants, but a comparator is needed for a direct estimate of how outcomes differ under another treatment condition. This distinction prevents descriptive counts or response measures from being mistaken for causal evidence.
Finally, the record reports numerous outcome measures and analyses, while leaving key details about multiplicity, missing data, and the statistical plan unreported. Recognizing those gaps is part of statistical interpretation, not a judgment about the conduct of the study. The registry allows readers to identify the endpoint framework and selected safety counts, while the absence of numerical primary and secondary efficacy results limits conclusions about the study's activity findings.
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 registry information does not include the numerical result for the primary AUClast endpoint, its geometric coefficient of variation, a confidence interval, or the number of participants contributing to that analysis. It also does not report numerical results for the listed secondary clinical outcomes. This prevents assessment of the magnitude and precision of pharmacokinetic or clinical findings from the registry record.
The single-arm, open-label design has no concurrent comparator. It therefore cannot provide a randomized estimate of the difference between ruxolitinib plus background treatment and another treatment. The absence of masking may be relevant to assessment of outcomes involving judgment or reporting; whether any outcome assessment was blinded is not reported in the registry record.
The trial planned four age groups, but on-treatment safety rows with participants at risk are listed for the first three groups only. The fourth group's safety row lists zero participants at risk. Enrollment and analysis details by age group, including whether the youngest group contributed pharmacokinetic data, are not reported in the registry record.
Other details needed to evaluate the analyses are also not reported: the sample-size justification, statistical models, multiplicity strategy, complete analysis-population definitions, missing-data methods, and interim-analysis plan. The pharmacokinetic analysis-set description is partial. For safety, the registry lists selected serious adverse-event terms and percentages but not their term-specific counts or denominators. These limitations constrain interpretation of precision, representativeness, and comparative risk.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Pharmacokinetics, Activity and Safety of Ruxolitinib in Pediatric Patients With Grade II-IV Acute Graft vs. Host Disease — NCT03491215.
- Registry record last updated 2025-05-04; status last verified 2025-05.
- Results first posted 2024-11-08.
- 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.
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18. Record Summary
NCT03491215 is a completed Phase I/II, open-label, multicenter, single-arm study sponsored by Novartis Pharmaceuticals. The registry lists enrollment of 45, a start date of 2019-02-21, and a primary completion date of 2021-03-11. The study evaluated ruxolitinib added to immunosuppressive treatment, including corticosteroids, in pediatric patients with grade II-IV acute graft-versus-host disease.
The primary Phase I endpoint was AUClast, summarized as a geometric mean with geometric coefficient of variation. Numerical results for this endpoint are not reported in the registry record. The record lists secondary response, pharmacokinetic, safety, duration-of-response, and steroid-dose outcomes but does not report their numerical results. On-treatment safety counts include serious adverse events in 24 of 45 participants and other adverse events in 45 of 45. Because the study had no comparator, its findings are descriptive rather than randomized treatment contrasts.