Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE (NCT05001737), a na phase 3 study. The primary outcome is Proportion of Subjects With Complete Response (CR) at Week 8 After First Administration of Emapalumab.

2. Clinical Question

The question is clinically and statistically specific: it concerns response at a defined follow-up time and uses a composite definition combining clinical assessment with laboratory criteria. The population spans MAS associated with Still's disease and MAS associated with SLE, which the record assigns to separate cohorts. These groups are not randomized arms and should not be treated as a controlled comparison. The endpoint therefore describes response in the treated study population; without a concurrent comparator, it cannot isolate the effect of emapalumab from other influences on participants' outcomes.

3. Trial Design

This is a phase 3, open-label, single-arm, multicenter study sponsored by Swedish Orphan Biovitrum. The registry lists an enrollment of 33 participants and a completed study status. The listed start date is 2021-12-15, and the primary completion date is 2024-06-30. There is no allocation to competing treatments, and masking is listed as none.

The record describes two cohorts: Cohort 1 for MAS in sJIA and AOSD, and Cohort 2 for MAS in SLE. Both cohorts receive emapalumab; the registry lists no separate comparator intervention. The adverse-event groups include 25 participants at risk in Cohort 1 and 8 in Cohort 2. These group sizes describe the safety record and should not be taken as evidence of a randomized comparison.

The primary endpoint is the proportion of all treated participants with complete response at week 8 after the first emapalumab administration. The record also lists secondary outcomes concerning glucocorticoid tapering, time to tapering, complete and overall response, MAS recurrence after complete response, and withdrawal due to lack of response. It lists 20 outcome measures overall, but no analysis entries are listed in the extract.

Because the trial is open-label and has a single group, participant and investigator expectations may be relevant to assessments, particularly clinical signs evaluated using a visual analog scale. The design can describe outcomes observed after treatment in this study population, but it does not offer a randomized control comparison. Details such as the protocol's sample-size justification, interim analyses and complete statistical 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.

Overall Study

Analysis population for the primary outcome, as defined in the registry: All treated

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.

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Subjects With Complete Response (CR) at Week 8 After First Administration of Emapalumab, measured over 8 weeks.

The primary endpoint is the proportion of subjects with complete response at week 8 after the first administration of emapalumab. The population is described as all treated. The response definition combines clinical and laboratory criteria: it requires resolution of clinical signs and symptoms present at baseline and normalization of laboratory parameters relevant to MAS.

Clinical MAS activity is assessed on a 10 cm visual analog scale. A clinical sign is considered resolved when its score is at or below 1/10. The listed laboratory requirements include WBC above the lower limit of normal (LLN), platelet count above LLN, LDH below 1.5 times the upper limit of normal (ULN), ALT below 1.5 times ULN, AST below 1.5 times ULN, fibrinogen above 100 mg/dL, and a ferritin level decreased by at least 80 % from screening or baseline, whichever is higher, or below 2000 ng/ml, whichever is lower.

A composite endpoint is used to summarize more than one dimension of response. Here, clinical improvement alone would not satisfy the stated definition if the required laboratory normalization were absent, and laboratory values alone do not capture the specified clinical assessment. The endpoint gives a defined response status at a particular follow-up time. However, the registry record does not report how many treated participants met this definition or the resulting proportion, so the endpoint definition can be described but the observed response cannot be interpreted from this record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical interpretation starts with the design. This study is a single-group, open-label phase 3 study, not a randomized comparison. A single-group result summarizes outcomes among participants who received the intervention; it does not directly estimate a contrast between treatment strategies. Random allocation is absent, and the registry lists masking as none. These features limit the kinds of causal conclusions that can be drawn from any response or safety summary.

What does a proportion summarize?

For a binary endpoint such as complete response, each participant is classified according to whether the stated response criteria were met at the specified assessment. The proportion is the number classified as responders relative to the relevant analysis population. In this record, the primary population is described as all treated, and the assessment is at week 8 after the first administration. The registry record does not report the responder count or the proportion, so no numerical primary estimate can be interpreted.

Even when a proportion is available, it is an estimate based on the participants observed in the study, not a guarantee that the same proportion would be seen in every similar population. A confidence interval, if reported, would express the uncertainty around an estimate under the statistical method used. A narrower interval generally indicates greater precision, while a wider interval indicates greater uncertainty. No primary confidence interval is reported in the registry record.

How should the composite response be read?

Complete response is defined using both clinical and laboratory requirements. The clinical component considers resolution of baseline signs and symptoms, with clinical activity measured on a visual analog scale and resolution defined at or below 1/10. The laboratory component specifies WBC and platelet counts above LLN; LDH, ALT and AST below 1.5 times ULN; fibrinogen above 100 mg/dL; and the stated ferritin condition. Because the endpoint is composite, the overall response classification relies on the combination specified in the registry, rather than on any single laboratory value alone.

Composite endpoints can capture several aspects of disease status in a single summary. They can also conceal variation among components: the overall response result does not, by itself, show which component was most often met or which one most often prevented a complete response. Component-level results would be needed to describe those patterns. Such component results are not reported in the registry record.

What does the study design allow?

In general, randomization helps balance measured and unmeasured factors between comparison groups. Because this study has no randomized comparator, its observed outcomes cannot distinguish treatment-associated change from the natural course of illness, concurrent care, measurement variation or other influences. The open-label design also means participants and study personnel know the intervention being given. That knowledge may be relevant to assessments involving judgment, including clinical activity scoring. These are design considerations, not claims that any particular bias occurred.

The two disease cohorts should be interpreted descriptively. Cohort 1 concerns sJIA and AOSD, while Cohort 2 concerns SLE. A difference in outcomes between them, if reported, would not be a randomized comparison and could reflect differences between the populations or their disease contexts. The record does not present an analysis comparing these cohorts.

What do the sample-size illustrations mean?

The page includes calculated sample-size material as a planning illustration based on the observed effect, not the trial's own design. The stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the effect to detect is a stated fraction of the observed effect. For time-to-event tables, the figures represent total events using the Schoenfeld approach; other tables represent participants per arm. These hypothetical calculations do not describe the actual single-arm design, and they are not observed power. The registry record does not report the study's sample-size justification or the assumptions used in its own planning.

For a binary outcome, a planning calculation depends on the assumed response levels and the effect to be detected, as well as the chosen error rate and allocation. Illustrative values can show how planning requirements change under specified assumptions, but they do not validate an analysis or establish that the study had adequate precision. Since no primary response estimate is reported in this record, the interpretation of any planning display must remain separate from the missing primary outcome result.

What can be inferred from safety summaries?

Serious adverse-event counts describe participants affected within each cohort, while event terms may describe the types recorded. A count of participants with at least one event is not necessarily a count of all event occurrences. The registry extract lists participants at risk, participants affected and deaths by cohort, but does not supply all details needed to reconstruct event timing, recurrent events, exposure-adjusted rates or causal attribution. The figures are therefore descriptive, and cross-cohort contrasts should not be read as comparative safety estimates.

The registry lists 20 outcome measures and zero analysis entries in the extract. This does not establish that the investigators performed no analyses; it means analyses are not listed in the registry record excerpt represented on this page. A full account of model choices, confidence interval methods, handling of repeated measures, covariate adjustment and prespecified analysis populations is not reported in the registry record.

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("Cohort 1 (sJIA and AOSD)", "Cohort 2 (SLE)")
n      <- c(25, 8)
events <- c(11, 4)
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  Cohort 1 (sJIA and AOSD)  25  11  44.0  24.4  65.1  26.7  62.9  26.6  63.1
ARM  Cohort 2 (SLE)  8  4  50.0  15.7  84.3  21.5  78.5  21.2  78.8

11. Multiplicity, Missing Data and Analysis Populations

The record lists 20 outcome measures, including the primary complete-response endpoint and secondary outcomes concerning glucocorticoid tapering, time to response, overall response, recurrence and withdrawal due to lack of response. When a study assesses multiple outcomes or performs multiple comparisons, the chance of a nominally notable result arising by chance can increase. Statistical methods may address multiplicity, but the approach used for this study is not reported in the registry record. The zero analysis entries in the extract do not establish whether multiplicity procedures were used.

The registry identifies the primary outcome population as all treated and gives the primary assessment time as week 8 after the first administration. It does not report a full analysis plan, a sample-size justification, interim analyses, the treatment of missing primary outcome values, or whether sensitivity analyses were planned. The status of incomplete follow-up and the number of participants with an evaluable primary assessment are also not reported in the registry record.

Missing data matter because a response proportion depends on how participants without an observed assessment are handled. Excluding them, classifying them as nonresponders, or using another method can lead to different estimates. These are general statistical considerations; the approach used is not reported in the registry record. The record also does not describe the analysis populations for secondary outcomes beyond the primary endpoint's all-treated population. Readers should therefore avoid assuming that every listed outcome used the same participants or missing-data rule.

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: still's disease (24.0%), pneumonia (20.0%), condition aggravated (16.0%), lupus nephritis (12.5%), abscess limb (12.5%).

The serious adverse-event summaries are organized by cohort. In Cohort 1 (sJIA and AOSD), 25 participants were at risk and 18 were affected by serious adverse events; 2 deaths are listed. In Cohort 2 (SLE), 8 participants were at risk and 4 were affected by serious adverse events; 0 deaths are listed. These figures describe participants in the study groups, not a comparison with an untreated or alternative-treatment group.

The record also lists other adverse-event participants: 24 of 25 in Cohort 1 and 8 of 8 in Cohort 2. The listed serious-event terms include Still's disease (24.0%), pneumonia (20.0%), condition aggravated (16.0%), lupus nephritis (12.5%), abscess limb (12.5%) and prothrombin level decreased (12.5%). The registry extract does not specify enough detail to interpret these percentages as event rates over time or to assign causal relationships. A serious adverse event is a safety-reporting category; its appearance in the record does not by itself mean the intervention caused it. These summaries should be read as descriptive safety information, with cohort size and the limits of the registry detail in view.

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

The study addresses emapalumab in children and adults with MAS associated with Still's disease or SLE, in the context described by the registry as inadequate response to high dose glucocorticoid treatment. It is a phase 3, open-label, single-arm study with an enrollment of 33. The record defines a complete response endpoint at week 8 and gives detailed clinical and laboratory criteria. It also provides cohort-specific safety summaries and lists secondary outcomes.

What the posted record does not provide is the observed primary response result. It contains no reported count or proportion of participants who achieved complete response at week 8. It therefore cannot support a numerical description of primary response frequency or its precision. The completed study status does not fill this gap, and the outcome definition should not be mistaken for evidence that the endpoint was achieved.

Even if a response estimate is available in another display, the single-arm design would still need to guide interpretation. A response proportion can describe outcomes among treated participants, but without a control group it cannot establish what would have happened under another treatment or without emapalumab. The open-label structure and clinical assessment component are also relevant when considering how outcomes were measured.

The safety summaries report participants affected and deaths by cohort, but these figures are descriptive. They do not establish whether emapalumab caused any listed event. Nor do the cohort summaries amount to a randomized safety comparison. Overall, this registry record is useful for understanding the study question, design, endpoint definition and reported safety counts, while important outcome and methods details remain unavailable. The interpretation should remain bounded by what the record actually reports.

14. Why This Trial Matters Statistically

This trial is statistically notable because it asks a focused response question in two clinically distinct MAS contexts while using a single-group, open-label design. The primary endpoint combines clinical assessment with laboratory criteria, making its operational definition central to interpreting any response estimate. The registry gives that definition in detail, including a visual analog scale criterion and specified laboratory thresholds.

The study also illustrates the distinction between outcome definition and outcome reporting. A precise endpoint can make the intended measure understandable, but it does not reveal the observed result. Here, the registry record does not report the primary response count or proportion. That absence prevents readers from assessing the response frequency or its precision from this record, regardless of the completed status listed for the study.

The design raises familiar statistical questions about interpretation. Without randomization or a concurrent comparator, outcome summaries describe the treated cohort rather than a treatment contrast. Cohort labels based on underlying disease do not create comparable control groups. The open-label setting is also relevant to a clinical outcome measure that includes assessment of signs and symptoms.

Finally, the record lists several secondary outcomes and safety information, making clarity about analysis populations, missing data and multiplicity important. Those methods are not fully reported in the registry record. Sample-size illustrations on the page are planning tools under stated assumptions, not a reconstruction of the trial's own design process and not observed power. Together, these features show why statistical interpretation must consider the design and completeness of reporting, not just the label of the study phase or the detail of the endpoint definition.

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 central limitation for interpreting efficacy from this registry record is that the primary response result is not reported. The record defines complete response at week 8 but does not give the count, proportion or uncertainty interval. Although the study is marked completed, that status does not provide the missing outcome data.

The study has a single group, no randomized allocation and no masking. There is no concurrent control group for a like-for-like comparison, so descriptive outcomes cannot establish a treatment contrast. The two cohorts differ by disease context and should not be treated as comparator arms. The open-label design may also be relevant to the clinical component of the endpoint, which uses an assessment of clinical activity.

The endpoint is composite. The registry specifies several clinical and laboratory requirements, but the component-level results are not reported. Without them, readers cannot determine how the overall response classification relates to each individual component. The record also does not report the handling of missing primary assessments, the evaluable population, or the analysis methods for the listed secondary outcomes.

Other details important to a full statistical assessment are not reported in the registry record, including the protocol's sample-size justification, interim analyses, complete statistical analysis plan, multiplicity approach and details of outcome-specific analysis populations. Safety information is descriptive, and the registry extract does not provide all context needed to interpret event timing or causal attribution. These limitations concern what can be inferred from this record; they do not establish that additional study information does not exist elsewhere.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Evaluate Efficacy, Safety and Tolerability, PK and PD of Emapalumab in Children and Adults With MAS in Still's or SLE — NCT05001737.
• Registry record last updated 2026-08-26; status last verified 2026-02.
• Results first posted 2026-02-19.
• 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

NCT05001737 is a completed phase 3, open-label, single-arm, multicenter study sponsored by Swedish Orphan Biovitrum. It enrolled 33 participants and evaluated emapalumab in children and adults with MAS in Still's disease, including sJIA and AOSD, or in SLE. The listed study start date is 2021-12-15, and the primary completion date is 2024-06-30.

The primary outcome is complete response at week 8 after the first administration, among all treated participants. The record details the clinical and laboratory criteria but does not report the observed primary response result. It lists 20 outcome measures and no analysis entries in the extract. Safety summaries include serious adverse events, other events and deaths by cohort. As a single-arm study without a randomized comparator, the record supports descriptive interpretation rather than a like-for-like treatment comparison.