Study of Mepolizumab Autoinjector in Asthmatics: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study of Mepolizumab Autoinjector in Asthmatics (NCT03099096), a na phase 3 study. The primary outcome is Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram.

2. Clinical Question

3. Trial Design

This was a Phase III, open-label, single-arm, repeat-dose, multicentre study of a mepolizumab autoinjector in participants with severe eosinophilic asthma. The registry record lists enrollment of 159 participants. It describes an expected enrollment of approximately 158 participants in the study summary. The study began on 2017-05-04, had primary completion on 2017-11-30, and is listed as completed.

Participants were to receive mepolizumab 100 mg subcutaneously as three doses at 4-weekly intervals. The first and third administrations, at Week 0 and Week 8, were to be self-administered under observation at the clinic. The second administration, at Week 4, was to be self-administered outside the clinic and without observation. The study description allows administration by a caregiver in specified circumstances. The stated treatment period was 12 weeks, with an end-of-study assessment 4 weeks after the last dose; participation was described as lasting up to 18 weeks including screening.

The study was not blinded, and there was no randomized control group. Its primary endpoint concerns successful self-administration of the observed Week 8 dose with the pictogram labelling approach. The record also lists secondary outcomes on successful unobserved Week 4 self-administration under the pictogram and standard-label-only approaches. These label descriptions do not establish a randomized comparison, and no like-for-like control comparison is reported.

The record does not report a statistical analysis plan, a sample-size justification, or details of any interim analyses. It also does not provide the primary endpoint result. Consequently, the design and study objective can be described, but the degree of observed success and its precision cannot be assessed from 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: Of the total 181 participants screened, 22 were screen failures and 159 were enrolled in this open-label, single arm, repeat dose study of mepolizumab and attempted to self-administer at least one dose of study treatment.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: All Subjects (Safety) Population

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 Percentage of Participants With Successful Self-administration of Their Observed Third Dose at Week 8 - Autoinjector With Standard Label + Pictogram, measured over Week 8.

The primary endpoint is the percentage of participants with successful self-administration of their observed third dose at Week 8 using an autoinjector with standard labelling plus a pictogram. It is a binary participant-level outcome: each participant with an evaluable administration is classified according to whether the administration was successful, and the endpoint expresses the proportion meeting that definition. The registry record describes the endpoint unit as percentage of participants.

This endpoint addresses whether participants or caregivers could use the device correctly during an observed administration. It is distinct from a measure of asthma control, symptom change, or comparative treatment efficacy. Observation in clinic means site staff were present for the Week 8 administration, so the endpoint reflects performance in that setting. The Week 4 administration was unobserved and is addressed by secondary outcomes, not by the primary endpoint.

The outcome description does not give the operational criteria used to classify an administration as successful. Those criteria, the number of participants with Week 8 data, the observed percentage, and a confidence interval are not reported in the registry record. The record says that only participants with data available at Week 8 were analyzed. Without the result and its denominator, it is not possible to quantify the observed success rate or how precisely it was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry record identifies a percentage endpoint, but does not report its observed value, confidence interval, analysis details, or a statistical analysis plan. The explanations below describe general statistical concepts relevant to a binary percentage endpoint; they do not fill in missing trial-specific methods.

What does a percentage endpoint represent?

For a binary outcome, each eligible participant contributes an outcome classified into one of two categories, such as successful or not successful administration. The percentage summarizes the share classified as successful within the analysis population. Its interpretation depends on the definition of success and on which participants are included in the denominator. In this study, the primary endpoint is described as the percentage with successful self-administration of the observed Week 8 dose under the pictogram labelling approach. The operational success criteria are not reported in the registry record.

A percentage is a descriptive estimate, not a guarantee that the same proportion would be observed in another group of participants or another setting. Sampling variability means that an estimate from a study can vary from the underlying rate in the population. A confidence interval is a range calculated using a statistical procedure to express uncertainty around an estimate. Its width depends on factors including the number of evaluable observations and the observed outcome frequency. Neither the estimate nor an interval for the primary endpoint is reported in the registry record, and no interval can be inferred from the enrollment count alone.

Why does the analysis population matter?

The primary outcome description says only participants with data available at Week 8 were analyzed. This means the endpoint denominator is tied to Week 8 availability, rather than necessarily including everyone enrolled. The registry record does not state how many participants had endpoint data or how missing outcomes were handled. If people with missing assessments differ from those assessed, a complete-case percentage may not represent the full enrolled group. Statistical adjustment or imputation can sometimes be considered, but their appropriateness depends on assumptions about why data are missing and on a prespecified analysis plan. Such methods are not reported in the registry record.

The description of the safety population is also specific: it includes enrolled participants attempting at least one self-administration. This population definition should not automatically be assumed to be the same as the endpoint analysis population. The registry record does not provide enough detail to reconcile the participant sets or to determine the flow from enrollment to Week 8 assessment.

What can an open-label, single-arm study estimate?

A single-arm study can describe outcomes observed among participants receiving the study intervention. Without a concurrent control group, it cannot isolate the intervention’s effect from other influences through a randomized comparison. Open-label conduct means participants and study staff were not masked to the intervention. For an outcome involving device use, observation and awareness of the study context may be relevant to performance and assessment. The record does not report independent blinded assessment or any adjustment intended to address these considerations.

The label descriptions in the registry record identify a pictogram-plus-standard-label approach and a standard-label-only approach. The study is nevertheless listed as single-arm, and allocation is not applicable. Those descriptions alone do not establish randomized assignment, balance between groups, or a planned comparative analysis. No statistical comparison between labelling approaches is reported in the registry record.

How should planning illustrations be read?

Sample-size illustrations are planning calculations, not observed results. The stated illustration assumptions use a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation, with the target effect expressed as a fraction of the observed effect. The record also distinguishes calculations reported as participants per arm from time-to-event calculations reported as total events. Those assumptions describe illustrations for planning and do not describe this trial’s single-arm design. The observed effect, the target fractions, and numerical illustration results are not reported in the registry record. Such planning quantities are not observed power and should not be interpreted as evidence that the trial had a particular probability of detecting an effect.

More broadly, a significance level is a chosen threshold used in some hypothesis-testing procedures; it does not measure the size or importance of an effect. A normal approximation is a mathematical simplification used to estimate sampling behavior under specified conditions. Equal allocation is a design assumption for a two-arm planning calculation, not a feature that can be attributed to this single-arm trial. The registry record does not report that these assumptions formed the trial’s own design or analysis plan.

What is not available for statistical appraisal?

The registry record lists no reported analyses. It does not provide the primary endpoint estimate, its denominator, a confidence interval, a hypothesis test, or a detailed statistical plan. It does not report methods for missing data, adjustment for covariates, subgroup analysis, or multiplicity control. These absences limit assessment of the endpoint’s precision and of how the analysis was conducted. They should not be replaced by assumptions about usual practice or by calculations from enrollment alone.

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("Mepolizumab Liquid Autoinjector")
n      <- c(103)
events <- c(102)
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  Mepolizumab Liquid Autoinjector  103  102  99.0  94.7  100.0  94.7  99.8  94.8  99.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists one primary endpoint and secondary outcomes concerning successful self-administration of the unobserved Week 4 dose under the pictogram and standard-label-only approaches. It does not report a statistical analysis plan, a testing hierarchy, or a method for controlling multiplicity. When several outcomes are tested, the chance of at least one apparently unusual result can increase if each is interpreted as a separate confirmatory test. Whether that issue applies to formal testing cannot be determined because the record does not report inferential analyses or their intended role.

The primary endpoint description states that only participants with Week 8 data were analyzed. The number with available data, the extent and reasons for missingness, and any missing-data method are not reported in the registry record. It is therefore unclear how the endpoint denominator relates to enrollment, or whether any missing outcomes were excluded, imputed, or handled another way. No assumption about the missing outcomes should be made.

The safety population is described as all enrolled participants attempting at least one self-administration. That definition differs in wording from the primary endpoint’s Week 8 data-available population. The registry record does not report participant flow or specify whether the populations overlap completely. This distinction matters because outcome and safety counts can use different denominators and answer different questions.

No subgroup analyses, sensitivity analyses, or interim analyses are reported in the registry record. Their absence from the record does not establish whether they were conducted; it means their methods and results are not reported there. The available information is insufficient to judge multiplicity procedures or the robustness of the primary endpoint to missing data.

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 3% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: alveolitis allergic (0.6%), asthma (0.6%), pneumothorax (0.6%), chest discomfort (0.6%), cervical vertebral fracture (0.6%).

The registry record reports safety counts for the mepolizumab liquid autoinjector group. Serious adverse events affected 4 of 159 participants at risk, and other adverse events affected 27 of 159 at risk. The record reports 0 deaths. These are participant counts as recorded, not estimates of comparative risk, because the study had no control group.

The listed serious-event terms each have a reported frequency of 0.6%: Alveolitis allergic, Asthma, Pneumothorax, Chest discomfort, Cervical vertebral fracture, and Facial bones fracture. These terms describe events recorded in the registry. The listing does not establish that each event was caused by mepolizumab or by the autoinjector. Nor should the listed terms be added together to infer a total, since the registry record does not state whether participants could have more than one event or how event terms relate to the participant counts.

Serious adverse events and other adverse events are different reporting categories. The registry record does not provide event-level timing, duration, severity details beyond the serious classification, or causal assessments. The counts therefore describe reported safety experience in this study group, but they do not establish a comparative safety profile or explain the cause of individual events.

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

The study addresses practical use of a mepolizumab autoinjector, with the primary endpoint focused on successful self-administration of an observed Week 8 dose using a pictogram-plus-standard-label approach. Its design is suited to describing what happened among participants in that study setting. The registry record does not report the primary endpoint result, however, so it does not reveal the observed percentage of successful administrations or the uncertainty around that percentage.

Even if an endpoint percentage were available, its meaning would be limited to the endpoint definition, the participants included in the analysis, and the study conditions. The Week 8 dose was administered under observation in clinic. The Week 4 dose was unobserved and is addressed by secondary outcomes. These settings are not interchangeable: observed use and use outside the clinic can differ in the assistance available and in how administration is assessed. The operational criteria for successful administration are not reported in the registry record.

The single-arm, open-label design does not establish how outcomes would compare with a different device, labelling approach, training method, or treatment. The different labelling descriptions do not, on their own, establish a randomized comparison. The registry record also does not report a statistical analysis plan or endpoint analysis results. Thus, neither a comparative effect nor a formal test of differences can be interpreted from the information recorded.

The safety counts provide a separate description of adverse events observed in the study group. They do not determine whether events were caused by treatment, and without a control group they cannot establish relative safety. The record reports no deaths and lists serious and other adverse-event counts, but does not include the detail needed to attribute individual events.

In short, the registry record describes a study intended to evaluate repeat autoinjector use and reports selected safety information. It does not report the primary success percentage, its denominator, or its confidence interval. It therefore does not support a numerical conclusion about the primary endpoint, its precision, or comparisons with alternatives.

14. Why This Trial Matters Statistically

Device-use outcomes differ from many clinical endpoints because the central question is whether a participant can complete an administration correctly, rather than whether a symptom or biological measurement changes. A clearly defined binary measure can make such a question understandable, but its statistical interpretation still depends on the success criteria, the assessment setting, and the analysis population. In this trial, the primary endpoint concerns the observed Week 8 administration, while an unobserved Week 4 administration is described by secondary outcomes.

The design also illustrates the boundary between description and comparison. A single-arm study can document observed use under its study procedures, but it cannot provide a randomized estimate of what would have happened under an alternative device or labelling approach. The registry record names two labelling approaches, yet lists the study as single-group and does not report a like-for-like control comparison. This makes it important not to read label descriptions as evidence of a comparative design.

Missing endpoint information is itself consequential for interpretation. Enrollment does not reveal how many participants contributed Week 8 data, what proportion met the success definition, or how precise the estimate was. The registry record does not report the primary result or the methods needed to judge missing observations. Those omissions prevent a statistical assessment of the main device-use question, despite the study’s completed status.

Finally, the safety counts show why outcome categories and denominators need to be kept distinct. Serious events, other adverse events, and successful administration are different endpoints, with potentially different analysis populations. The record reports selected counts but does not provide a control group or causal attribution. A careful statistical reading therefore separates the study’s practical question, its descriptive design, and the limited results recorded.

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 main limitation for interpreting the primary question is that the registry record does not report the Week 8 success percentage, its denominator, or an uncertainty interval. The endpoint description also does not state the operational criteria used to classify an administration as successful. Without those details, neither the outcome magnitude nor its precision can be assessed.

The study is open-label and single-arm, with no randomized control group reported. This limits interpretation to observed experience under the study procedures and does not support a controlled comparison with another treatment or device. Although the record describes more than one labelling approach, it does not establish a randomized comparison between them.

The primary endpoint includes only participants with Week 8 data available, but the number with such data and the handling of missing outcomes are not reported. The record also does not give participant flow or explain how the endpoint analysis population relates to the safety population. This leaves uncertainty about the denominator and the possibility that participants with missing data differed from those assessed.

The registry record does not report the statistical analysis plan, a sample-size justification, interim analyses, multiplicity procedures, or detailed endpoint analyses. It also does not report event-level safety details or causal assessments. These omissions constrain evaluation of both the primary result and the safety findings; they should not be filled in by assumptions about standard practice.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Study of Mepolizumab Autoinjector in Asthmatics — NCT03099096.
• Registry record last updated 2023-06-28; status last verified 2023-06.
• Results first posted 2018-06-29.
• 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

NCT03099096 is a completed Phase III, open-label, single-arm, multicentre study of a mepolizumab subcutaneous autoinjector in severe eosinophilic asthma. Enrollment was 159 participants. The study description specifies three 100 mg doses at 4-weekly intervals, with the Week 0 and Week 8 administrations observed in clinic and the Week 4 administration unobserved outside the clinic.

The primary endpoint concerns the percentage of participants who successfully self-administered the observed Week 8 dose using standard labelling plus a pictogram. The endpoint result, its denominator, and its precision are not reported in the registry record. The record also lists secondary outcomes for unobserved Week 4 administration under two labelling approaches, but does not report a randomized comparison or statistical analysis plan.

Safety reporting includes 4 participants with serious adverse events, 27 with other adverse events, and 0 deaths. The record does not establish causality. It describes the study’s purpose and selected safety information, but does not provide the primary endpoint result needed to assess the central device-use question.