A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG): Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG) (NCT03759366), a non-randomized phase 3 study. The primary outcome is Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment.

2. Clinical Question

The study was designed to evaluate efficacy, safety, pharmacokinetics, and pharmacodynamics of eculizumab in pediatric refractory generalized myasthenia gravis. For the primary question, the registry identifies change in QMG total score at Week 26 as the outcome of interest. QMG is a disease-severity measure; higher scores indicate more severe disease, so movement toward a lower score represents a lower measured severity.

The registry reports an enrollment of 12, while the primary outcome population is defined by eligibility, receipt of at least 1 dose, and evaluability. The number evaluable for the primary outcome is not reported in the registry record. The Week 26 change estimate and its uncertainty are also not reported in the registry record. Consequently, the record does not establish from the posted primary outcome data how much participants’ scores changed or how precisely any change was estimated.

3. Trial Design

This was a Phase 3, open-label, multicenter study of eculizumab in pediatric participants with refractory generalized myasthenia gravis. Its allocation is recorded as non-randomized, and its model as single-group. There was no masking and no concurrent control arm. The registry lists the study as completed and reports enrollment of 12.

The intervention was eculizumab by intravenous infusion. During the 26-week Primary Evaluation Treatment Period, the described schedule was weekly administration during an initial induction phase and every 2 weeks during the maintenance phase. During the Extension Period, which could last up to 208 weeks, participants were to continue treatment every 2 weeks. The duration of the initial induction phase and any further details not contained in the registry description are not reported in the registry record.

The study began on 2018-12-28, and the primary completion date is 2022-01-06. The registry identifies change from baseline in QMG total score at Week 26, regardless of rescue treatment, as the primary outcome. Secondary outcomes include MG-ADL, MGC, EQ-5D-Y VAS, and Neuro-QoL Pediatric Fatigue measures, as well as threshold reductions in MG-ADL and QMG scores with and without rescue treatment. The registry lists 15 outcome measures.

Because participants were not randomized between treatment and control groups, changes over time cannot be separated from all other explanations using a between-group contrast. The design can describe outcomes among participants receiving eculizumab, but it does not provide a randomized estimate of what would have happened to a comparable group without the study treatment. The registry record does not report a comparator-based efficacy analysis.

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: All participants were offered participation in the Extension Period of the study.

Primary Evaluation Period (26 Weeks)

Reasons for not completing this period:

Extension Period (Up to 208 Weeks)

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Modified Full Analysis Set: all participants 12 to \<18 years of age who received at least 1 dose of eculizumab. Here, 'Overall Number of Participants Analyzed' signifies those participants who were evaluable for this outcome measure.

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: Safety Analysis Set: all participants who received at least 1 dose of eculizumab.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in the QMG Total Score at Week 26 Regardless of Rescue Treatment, measured over Baseline, Week 26.

The primary endpoint is change from baseline in the QMG total score at Week 26, regardless of rescue treatment. QMG is a disease-severity scale with 13 items covering ocular, facial, bulbar, gross motor, axial, and respiratory functions. Each item is graded from 0 to 3, with higher item scores indicating greater severity. The total score ranges from 0 to 39, and higher total scores indicate more severe disease.

Change from baseline compares a participant’s score at follow-up with that participant’s starting score. This focuses the outcome on change over the treatment period rather than the Week 26 score alone. As a general statistical point, baseline-adjusted change measures can help describe how scores move within participants, but interpretation still depends on the analysis method, the number of evaluable participants, and the uncertainty around the estimate. Those result details are not reported in the registry record.

QMG is used as a structured measure of disease severity. Its specified item content and scoring make the endpoint interpretable as a change on a defined clinical scale. A lower score corresponds to less severe measured disease; however, without the posted Week 26 estimate and its uncertainty, the magnitude and precision of any change cannot be assessed from the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry describes the primary outcome as a mean change in a continuous score, with standard deviation as the measure of dispersion. A mean is the arithmetic average of the analyzed observations. A standard deviation describes how spread out individual observations are around that average. These are different kinds of information: the mean describes the group’s average change, while the standard deviation describes variability among participants.

What does a change score represent?

For each participant, change from baseline represents the follow-up score relative to that participant’s baseline score. The group mean change then summarizes those individual changes. Since higher QMG scores indicate more severe disease, a movement toward lower scores represents a reduction in measured severity. The registry’s primary endpoint is assessed at Week 26 and includes participants regardless of rescue treatment. The observed mean change and standard deviation are not reported in the registry record, so the actual result cannot be interpreted numerically.

As a general statistical explanation, a confidence interval describes uncertainty around an estimate under the assumptions of the statistical method. It is not a range containing a known proportion of individual participant scores. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. No confidence interval for the primary outcome is reported in the registry record. No p-value for that outcome is reported there either, so statistical significance cannot be assessed from the registry information.

Why does the study structure matter?

This is a single-group, non-randomized study with no masking. In a randomized comparison, differences between groups can help estimate how outcomes differ under assigned treatment conditions, subject to the study’s assumptions and limitations. Here, the registry reports no separate comparison group. A change over time within the treated group is descriptive, but it cannot isolate the effect of treatment from other possible influences on participants’ scores. The open-label design means that participants and study personnel were not masked to treatment assignment; further details about how QMG assessments were conducted are not reported in the registry record.

As a general concept, randomized allocation can reduce systematic differences between treatment groups at the time of assignment, while masking can reduce some influences of knowledge of treatment assignment on reporting or assessment. Neither feature is present in the design as recorded. That does not make the observed scores meaningless, but it places limits on causal interpretation. The record does not report a statistical adjustment intended to address the absence of a control group.

How should variability be read?

Participant responses may vary even when everyone receives the same intervention. The standard deviation is one way to describe that variation for a continuous outcome. It is not the standard error of the mean and does not directly express uncertainty about the average. The standard error and a confidence interval would depend on the analysis sample and statistical method. Those results are not reported in the registry record. The number of participants evaluable for the primary endpoint is also not reported, which further prevents reconstruction of precision.

Over-dispersion is a general concern for count outcomes when variability exceeds what a simple count model assumes. It is not the main framing for this continuous QMG change endpoint, which the registry specifies as a mean with standard deviation. For continuous data, the key interpretive questions include the distribution of participant changes, the presence of unusual values, and the suitability of the analysis assumptions. The registry record does not report diagnostic checks or a detailed model, so no claim about those features can be made.

What can planning illustrations tell readers?

Sample-size planning calculations are prospective illustrations of the number of participants that might be needed under stated assumptions; they are not observed results and are not observed power. The planning assumptions described for this study’s accompanying illustrations include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the effect to detect expressed as a fraction of the observed effect. The registry record does not report those calculations as the study’s own design justification. They should not be read as evidence that the study was designed with a particular power or as an estimate of the probability that a result is true.

The design recorded for the trial is single-group, so a hypothetical two-arm planning illustration does not describe the actual allocation used in the study. Any sample-size value in such an illustration would be conditional on its planning assumptions and would not change the fact that the registry describes no randomized control group. The protocol’s sample-size justification is not reported in the registry record. Interim analyses and a detailed statistical analysis plan are also not reported in the registry record.

The registry lists 15 outcome measures and two analyses. The exact methods used for each analysis, including any covariate adjustment or model specification, are not reported in the registry record. Consequently, statistical explanations of means, variability, confidence intervals, and design limitations are general guidance rather than a reconstruction of an undocumented analysis.

10. Confidence Intervals for Each Arm

No two-arm comparison is shown for this trial, but each arm's mean can be given with a t-based 95% confidence interval computed from the posted mean, spread and number of participants.

R code and output

arm <- c("Eculizumab")
n   <- c(10)
m   <- c(-6.1)
sp  <- c(4.56)
sd  <- sp      # posted standard deviations
for (i in seq_along(n)) {
  se <- sd[i] / sqrt(n[i]); h <- qt(0.975, n[i] - 1) * se
  cat(sprintf("CARM|%s|%d|%.3f|%.3f|%.3f|%.3f\n", arm[i], n[i], m[i], sd[i], m[i] - h, m[i] + h))
}

CARM  Eculizumab  10  -6.100  4.560  -9.362  -2.838

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 15 outcome measures, including the primary QMG change endpoint and secondary measures of daily activities, composite symptoms, quality of life, fatigue, and threshold score reductions. It also lists two analyses. The record does not report how the analyses relate to the outcomes or whether the outcomes were organized into a prespecified testing hierarchy.

When several outcomes or statistical tests are considered, the chance of at least one apparently notable result can increase. As a general statistical approach, multiplicity procedures can control that risk, or an analysis plan can distinguish confirmatory outcomes from exploratory ones. Whether any correction or hierarchy was used is not reported in the registry record. The registry record also does not report a detailed statistical analysis plan or interim analyses.

Missing-data handling is not reported in the registry record. In particular, the record does not specify how missing Week 26 QMG scores, incomplete assessments, or discontinuations were handled in the primary analysis. It also does not report sensitivity analyses addressing missing outcomes. These details matter because the interpretation of a mean change depends on which participants contribute data and how unavailable measurements are treated.

The primary analysis population is described as participants 12 to <18 years of age who received at least 1 dose of eculizumab, with the overall number analyzed referring to those evaluable for the outcome. The actual number evaluable is not reported in the registry record. Enrollment is 12, but that enrollment figure does not establish how many participants contributed to the primary endpoint. The criteria used to determine evaluability beyond the stated description are not reported in the registry record.

Rescue treatment is included in the primary endpoint regardless of its use. The registry lists secondary threshold outcomes both with no rescue treatment and regardless of rescue treatment, but does not report the detailed analysis rules for those outcomes. These gaps prevent a full assessment of the estimand, multiplicity control, and robustness to missing observations.

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: pyrexia (9.1%), peritonsillar abscess (9.1%), myasthenia gravis (9.1%), myasthenia gravis crisis (9.1%), suicide attempt (9.1%).

The registry reports 11 participants at risk for serious adverse events and 4 affected by at least one serious adverse event. It also lists 11 participants at risk for other adverse events and 11 affected. No deaths are reported. These figures describe counts in the eculizumab group; they are not comparisons with an untreated or alternative-treatment group.

The listed serious adverse event terms are pyrexia, peritonsillar abscess, myasthenia gravis, myasthenia gravis crisis, and suicide attempt. Each term is reported at 9.1%. These are registry-listed terms and percentages; the record does not provide further event-level details in the information summarized for this trial. A term’s percentage should not be treated as a measure of severity or duration.

As a general statistical point, participant counts and event counts are not necessarily interchangeable: one participant can experience more than one event or event type. The record’s affected-participant counts describe how many participants were recorded as affected, while the listed terms describe serious-event categories. With no control group, these figures cannot quantify a comparative risk or establish whether an event was caused by treatment. The registry record does not report further details needed to assess timing, duration, or individual outcomes for these events.

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

The study addresses an important descriptive question: how QMG scores and other outcomes were assessed during eculizumab treatment in pediatric participants with refractory generalized myasthenia gravis. The registry identifies a Week 26 primary endpoint, defines the QMG scale, and records a safety experience. Those details help readers understand the intended measurement and the design in which it was collected.

However, the registry record does not report the primary outcome estimate, its standard deviation, the number analyzed, or an interval estimate. It therefore does not show the magnitude or precision of the mean QMG change. The absence of those statistics means that a reader cannot determine from this record whether the average score moved upward or downward, how variable participant changes were, or how uncertain the estimate was.

Even if a within-group change estimate were available, the single-group, non-randomized design would not provide a randomized comparison. As a general principle, an observed before-and-after change can be described, but it does not by itself identify what caused that change. The open-label design and lack of a comparator also limit interpretation of subjective or assessment-dependent outcomes.

The safety counts are useful as a description of events recorded among participants in the study. They do not establish comparative safety, because no control group is reported. The small enrollment of 12 also means the study’s size is limited for characterizing uncommon events; this is a general limitation of small studies, not a calculation of risk from these data.

Accordingly, the record documents the study’s purpose, methods, endpoints, and selected safety counts, but does not provide enough outcome information for a quantitative interpretation of the primary endpoint. It should not be read as demonstrating a treatment effect or its absence. The registry record does not report the results needed to make either claim.

14. Why This Trial Matters Statistically

This trial is statistically notable for the population and design it records: a Phase 3 study of eculizumab in pediatric participants with refractory generalized myasthenia gravis, conducted as an open-label, non-randomized, single-group study. The registry describes an enrollment of 12 and a defined primary outcome at Week 26. These features make clear both the focused scope of the investigation and the limits of what its design can establish.

QMG is a structured, multi-item score with a defined range and direction. Stating that higher scores indicate more severe disease helps readers interpret the endpoint’s direction without confusing a higher score with improvement. The primary outcome is also explicitly framed regardless of rescue treatment, while selected secondary outcomes distinguish analyses with no rescue treatment from those regardless of rescue treatment. Those distinctions are relevant to defining what each outcome represents.

Statistically, the absence of a control group is central. A single-group study can describe observed trajectories, but it cannot provide a randomized between-group contrast. The registry record also does not include the primary estimate or its uncertainty, so readers cannot evaluate the size or precision of the reported endpoint from the available outcome information.

The record’s safety counts provide a separate descriptive dimension, including serious adverse events and deaths. They cannot support comparative risk estimates without a comparator. Together, the design, outcome definitions, and missing result details illustrate why statistical interpretation requires more than a named endpoint: sample size, analysis population, estimates, uncertainty, and design context all shape what can reasonably be concluded.

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 trial-specific limitation is its single-group, non-randomized design. There is no concurrent comparator in the registry record, so the study cannot estimate a randomized difference between eculizumab and another treatment or no treatment. Change from baseline, if reported, would remain a within-group description rather than a controlled treatment contrast.

The study is open-label, with no masking. The registry record does not report additional safeguards for outcome assessment, so the influence of awareness of treatment on assessment cannot be evaluated from the record. The study enrolled 12 participants, and the number evaluable for the primary outcome is not reported in the registry record. The primary analysis population is narrower than the overall enrollment description, requiring participants to be 12 to <18 years of age, to have received at least 1 dose, and to be evaluable.

Most importantly for interpretation, the primary outcome estimate and its precision are not reported in the registry record. The record also does not report the detailed statistical model, missing-data approach, multiplicity strategy, interim analyses, or protocol sample-size justification. Without these details, readers cannot independently assess the analysis assumptions, robustness, or the basis for the planned enrollment.

The registry describes a primary evaluation period of 26 weeks and an extension of up to 208 weeks. The primary endpoint is assessed at Week 26; the registry description does not provide the primary outcome result or enough information to interpret longer-term outcome patterns. The schedule’s induction duration and other details not included in the description are not reported in the registry record.

Safety counts are descriptive and have no concurrent comparison. The record does not report further event-level context in the information, such as timing or duration. These limitations mean the registry entry is informative about the study structure and selected counts, but insufficient for a full quantitative assessment of efficacy or comparative safety.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 3 Open-Label Study of Eculizumab in Pediatric Participants With Refractory Generalized Myasthenia Gravis (gMG) — NCT03759366.
• Registry record last updated 2024-12-11; status last verified 2024-12.
• Results first posted 2022-08-25.
• 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

The registry record describes a completed Phase 3, open-label, multicenter, non-randomized, single-group study of intravenous eculizumab in pediatric participants with refractory generalized myasthenia gravis. Enrollment was 12. The study began on 2018-12-28, with primary completion on 2022-01-06.

The primary outcome was change from baseline in QMG total score at Week 26, regardless of rescue treatment. The registry defines QMG as a 13-item scale ranging from 0 to 39, with higher scores indicating more severe disease. The primary outcome estimate and its uncertainty are not reported in the registry record.

Safety information includes 4 participants affected by serious adverse events among 11 at risk, 11 affected by other adverse events among 11 at risk, and no deaths. The registry lists five serious-event terms at 9.1% each. Because the study has no control group, these figures are descriptive rather than comparative.