A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist (NCT02808819), a non-randomized phase 3 study. The primary outcome is Change From Baseline in Basophils, Full Analysis Set.

2. Clinical Question

In practical terms, the study continued observation of people who had already participated in a predecessor benralizumab study. Its stated purpose was to characterize safety during further treatment and monitor pharmacodynamic activity. The primary endpoint selected for the posted results is a laboratory measure, not a direct measure of asthma symptoms or exacerbations. Other listed outcomes include asthma exacerbations, health care encounters due to asthma, blood eosinophil count, anti-drug antibody responses, and duration of exposure. Those outcomes provide additional areas of observation, but numerical results for them are not reported in the registry record. The study can therefore be described in terms of its population, treatment schedules, and planned endpoint, but its primary question cannot be answered from the posted numerical results.

3. Trial Design

MELTEMI, registered as NCT02808819, is a completed Phase 3, multicenter, open-label safety extension study. The registered title identifies adults with asthma receiving inhaled corticosteroid plus long-acting β2 agonist. The study enrolled 447 participants. Its stated purpose was to continue characterizing benralizumab safety and monitor pharmacodynamic activity among participants who remained on treatment in predecessor study D3250C00021 (BORA, NCT02258542) for at least 16 weeks and not more than 40 weeks.

The registry describes a parallel model with non-randomized allocation and no masking. Benralizumab was administered subcutaneously every 4 weeks in Arm A and every 8 weeks in Arm B. Both arms received benralizumab, so the design does not include a placebo or untreated group in the arm descriptions. The different schedules are not a randomized comparison: the record explicitly cautions that the arms are not a like-for-like control comparison. The registry does not report how participants came to be assigned to either schedule.

The study started on 2016-06-30, reached primary completion on 2020-06-18, and has completed status. These dates describe the registered study timeline; they do not provide the duration of an individual participant’s exposure. Duration of exposure is listed as a secondary outcome, but its numerical result is not reported in the registry record.

The registry lists 17 outcome measures and no analysis entries. The record gives a primary endpoint and names several secondary outcomes, but does not provide numerical results for the primary endpoint. This distinction matters: a completed study and a stated endpoint do not, by themselves, establish what the endpoint values were or how precisely any treatment-schedule difference was estimated.

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: 170 participants from SIROCCO(NCT01928771)/CALIMA(NCT01914757) assigned to Benralizumab 30 mg every 4 weeks (q4w) with 1 participant not treated. 178 participants from SIROCCO/CALIMA received Benralizumab every 8 weeks (q8w). 51 participants from ZONDA(NCT02075255) received Benralizumab q4w. 48 participants from study ZONDA received Benralizumab q8w.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full analysis set. For each lab test, number of patients is the number of patients with available change from baseline value.

5. Baseline Characteristics

The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.

Population: Full analysis set is defined to include subjects who received at least 1 dose of investigational product (IP).

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in Basophils, Full Analysis Set, measured over From Week 0 to Benralizumab is available in the local market or early discontinuation. Change from week 0 to the end of treatment period/early discontinuation is presented..

The primary endpoint is change from baseline in basophils, reported as a mean for the full analysis set. The measurement unit is 10^9 cells/L. The registry describes the endpoint as change in a hematologic laboratory parameter and specifies a timeframe from Week 0 to when benralizumab is available in the local market or early discontinuation; it also describes change from Week 0 to the end of the treatment period or early discontinuation. For each laboratory test, the number of patients is defined as the number with an available change-from-baseline value.

A change-from-baseline measure expresses how a participant’s later value differs from that participant’s starting value. In general, using change can help focus an analysis on the direction and magnitude of movement during observation, rather than only on a value at the end. A mean summarizes the average change in the analyzed participants. It does not show how much individual participants varied; the registry identifies standard deviation as the dispersion measure.

Basophils are one of the hematologic laboratory measures recorded in this study. As a pharmacodynamic endpoint, a laboratory change can describe biological activity during treatment, but it is not itself a direct measure of symptoms, exacerbations, or health care use. The registry record does not report the mean change, its standard deviation, a confidence interval, or a test of the primary endpoint. Consequently, the endpoint’s observed direction, size, and precision cannot be described from the posted results.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The primary endpoint is a continuous laboratory measure summarized as a mean. The registry describes change from baseline in basophils and identifies standard deviation as the dispersion measure. It defines the analyzed number for each laboratory test as the number of participants with an available change-from-baseline value. No actual mean, standard deviation, confidence interval, or test result for this endpoint is reported in the registry record.

What does a mean change describe?

In general, a change score is calculated by comparing a follow-up measurement with a baseline measurement for the same participant. A mean change then averages those participant-level changes among the participants included in the analysis. The mean is useful for conveying the group’s average direction and magnitude of change, but it does not imply that each participant changed by that amount. Individuals may have changes above, below, or opposite to the group average. The standard deviation describes the spread of participant values around the mean; it is not the same as uncertainty in the estimated mean.

The registry identifies Week 0 as the starting point and describes follow-up through the end of the treatment period or early discontinuation. It also refers to a period ending when benralizumab is available in the local market or at early discontinuation. The record does not clarify how these timeframe descriptions relate to each participant’s endpoint visit, nor does it report the distribution of follow-up times. The primary value should therefore be understood according to the registry’s stated endpoint description, without assuming a single fixed follow-up duration for all participants.

What would a confidence interval add?

In general, a confidence interval gives a range of values compatible with an estimate under the specified statistical model and sampling assumptions. It conveys precision: a narrower interval indicates a more precise estimate than a wider interval. It is not a guarantee that the true value lies in the interval, and it does not replace consideration of study design or possible bias. No confidence interval for the primary endpoint is reported in the registry record, so its precision cannot be assessed from the posted result information.

How should the two schedules be compared?

The design lists parallel arms with benralizumab given every 4 weeks or every 8 weeks. A between-arm contrast could describe a difference in observed outcomes, but the allocation was non-randomized. In general, randomization helps support causal interpretation because it reduces systematic differences between groups in expectation. With non-randomized allocation, observed group differences can be entangled with participant characteristics, prior treatment experience, clinical decisions, or other factors. The record does not report the allocation procedure, covariate adjustment, or a statistical model for comparing the schedules. An unadjusted contrast, if calculated from summary values elsewhere, would remain descriptive and would not by itself resolve confounding.

Open-label status indicates no masking. For laboratory endpoints, measurement may be more standardized than subjective outcomes, but interpretation still depends on collection, processing, and analysis procedures. Those procedures are not reported in the registry record. The record also does not describe any interim analyses, the statistical testing strategy, or the assumptions used for an analysis of the primary endpoint. These details should not be inferred from the phase designation or the fact that the study was completed.

What do the planning calculations mean?

General sample-size illustrations based on an observed effect are planning exercises, not descriptions of the trial’s achieved ability to detect an effect. The stated illustration assumptions are a two-sided significance level of 0.05, equal allocation between arms, and a normal approximation, with the target effect expressed as a stated fraction of the observed effect. For time-to-event illustrations, the total number of events is the quantity described; for other illustrations, the quantity is participants per arm. These assumptions describe the illustrations, not the original trial design. The registry record does not report that these assumptions were used to plan MELTEMI, and sample-size illustrations should not be called observed power. Because the primary observed effect is not reported in the registry record, the interpretation of any effect-based illustration must remain separate from the unreported primary result.

Over-dispersion is a general statistical concern when variability in observed data exceeds what a chosen model expects. If a model assumes less variation than the data contain, its uncertainty estimates can be too small and inference can appear more precise than warranted. Whether over-dispersion is relevant depends on the outcome and analysis model. The primary endpoint is a continuous laboratory measure, but no model specification or evidence about over-dispersion is reported in the registry record; it should not be assumed to have been assessed or found.

The registry lists 17 outcome measures, while the analysis entry count is zero. This means the record does not contain analysis entries describing statistical tests or model results. It does not establish that no analyses were performed outside the registry. Without analysis details, readers cannot verify which participants contributed to each estimate, how missing values were handled, whether adjustments were made, or how uncertainty was quantified. Those are material parts of interpreting an endpoint, rather than minor technical details.

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("Benra 30 mg q.4 Weeks", "Benra 30 mg q.8 Weeks")
n   <- c(173, 178)
m   <- c(0.014, 0.012)
sp  <- c(0.0229, 0.0243)
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  Benra 30 mg q.4 Weeks  173  0.014  0.023  0.011  0.017
CARM  Benra 30 mg q.8 Weeks  178  0.012  0.024  0.008  0.016

11. Multiplicity, Missing Data and Analysis Populations

The registry lists 17 outcome measures, including the primary basophil endpoint and secondary outcomes related to asthma exacerbations, asthma-related health care encounters, blood eosinophils, anti-drug antibody responses, and duration of exposure. When several outcomes are examined, the chance of obtaining at least one apparently notable result can increase if many statistical tests are conducted. In general, a prespecified hierarchy or multiplicity adjustment can help control how results are interpreted across multiple tests. The registry record does not report a multiplicity strategy, a testing hierarchy, or adjusted inferential results. No claim should therefore be made that a particular multiplicity approach was used.

The endpoint population is described as the full analysis set. For each laboratory test, the number of participants is defined as those with an available change-from-baseline value. This identifies an availability-based rule for the laboratory result, but the registry record does not report the full analysis set definition, the count contributing to the primary endpoint, or the amount and pattern of missing data. It also does not report whether missing values were imputed, whether participants with incomplete measurements were excluded, or what sensitivity analyses were conducted.

In general, missing data can affect both the number of observations and the interpretation of an estimate. If measurement availability is related to participant characteristics or outcomes, the analyzed participants may differ from those without measurements. The direction and extent of any effect depend on why data are missing and on the analytic approach. Those details are not reported in the registry record, so the impact of missing endpoint values cannot be evaluated.

The registry contains no analysis entries. As a result, the statistical methods used for the listed outcomes, any adjustment for baseline characteristics, and any handling of repeated or incomplete observations are not reported in the registry record. This limits the ability to assess how the reported endpoint population would translate into a particular analysis result.

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: asthma (5.8%), influenza (1.4%), asthenia (0.9%), lower limb fracture (0.9%), pneumonia (0.9%).

The safety record lists serious adverse event counts for each benralizumab schedule. In the every-4-weeks arm, 44 participants were recorded as affected among 220 at risk; in the every-8-weeks arm, 47 were recorded as affected among 226 at risk. The record also lists other adverse event counts: 169 among 220 at risk in the every-4-weeks arm and 145 among 226 at risk in the every-8-weeks arm. Death counts are 1 and 0, respectively. These are counts recorded for the arms, not causal conclusions.

The listed top serious adverse event terms include Asthma at 5.8%, Influenza at 1.4%, Asthenia at 0.9%, Lower limb fracture at 0.9%, Pneumonia at 0.9%, and Limb injury at 0.9%. The registry record does not provide the context needed to interpret each percentage’s denominator or to determine whether events were judged related to treatment. It also does not provide exposure-adjusted rates or a randomized control group.

In general, adverse events occurring during a study are not necessarily caused by the study treatment. Counts can describe what was recorded during observation, but comparisons between non-randomized groups may reflect differences in participants, follow-up, or other factors. The death counts do not establish cause of death, and the registry record does not report such attribution. These safety figures should therefore be read as descriptive registry reporting rather than as proof of causation or a direct estimate of comparative risk.

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

The record shows that MELTEMI was a completed, open-label, non-randomized Phase 3 extension study of benralizumab in adults with asthma who continued from a predecessor study. It reports two subcutaneous dosing schedules and defines a primary laboratory endpoint: mean change from baseline in basophils in the full analysis set. It also records selected adverse-event counts and names additional clinical and laboratory outcomes. These details establish what the study was designed to observe and what safety information is posted.

The record does not report numerical results for the primary endpoint. Without the observed mean change and a measure of its uncertainty, the direction, size, and precision of that result cannot be evaluated. It is not appropriate to infer that basophils changed or did not change, or to infer a statistically meaningful result, from the endpoint description alone. Numerical results for the named secondary outcomes are also not reported in the registry record.

The safety counts indicate participants recorded with serious and other adverse events in each arm, along with the recorded death counts. They do not establish that benralizumab caused any particular event. Nor should the two arm counts be treated as a definitive comparative safety estimate: allocation was non-randomized, the registry cautions that the arms are not a like-for-like comparison, and the record does not report an adjusted comparative analysis.

In general, a study’s design, outcome estimates, and uncertainty all contribute to interpretation. A completed study with a specified endpoint is not the same as a posted numerical result, and a numerical result would still need to be considered in light of the design and analysis methods. The registry does not report the statistical plan, analysis details, missing-data methods, or numerical endpoint estimates needed for a fuller assessment. The most defensible reading is therefore descriptive: the record identifies the extension’s aims, population, dosing schedules, endpoint, and selected safety counts, while leaving the primary efficacy-related laboratory result and its precision unreported.

14. Why This Trial Matters Statistically

This study illustrates why a registry description and an analysis result answer different questions. The record identifies the trial’s purpose, population, design, treatment schedules, and primary endpoint. It does not provide the numerical primary-endpoint result or inferential analysis. Recognizing that distinction prevents the study’s completed status or endpoint label from being mistaken for evidence about the observed outcome.

The non-randomized, open-label design also makes the comparison structure important. Two groups may receive different schedules, but their observed outcomes cannot automatically be attributed to schedule when allocation was not randomized. This is a general issue in clinical statistics: a contrast can be numerically descriptive without being a clean causal estimate. The registry itself warns that these arms are not a like-for-like control comparison.

The chosen primary endpoint is a laboratory measure summarized as a mean change, while the stated study purpose includes safety characterization and pharmacodynamic monitoring. That distinction matters because a laboratory endpoint answers a different question from patient-centered outcomes such as exacerbations or health care encounters. The latter are listed among secondary outcomes, but their numerical results are not reported in the registry record.

Finally, the safety information shows why counts need context. The record reports participants affected, top serious-event terms, and deaths, but those entries do not by themselves establish attribution or comparative risk. Without exposure-adjusted analyses, a randomized comparator, or reported causal assessments, these counts should be interpreted descriptively. Together, these features make MELTEMI a useful example of reading the design and reporting limits alongside the endpoint definition rather than treating a registry entry as a complete statistical analysis.

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 the primary endpoint is that its numerical result is not reported in the registry record. The record does not give the mean change in basophils, the standard deviation, a confidence interval, or an inferential test. Without those values, the observed endpoint and its precision cannot be assessed.

The arms were non-randomized and open-label. The registry explicitly cautions that they are not a like-for-like control comparison. It does not report the allocation process, baseline comparability, adjustment methods, or a model for comparing schedules. This limits causal interpretation of any apparent differences between arms. The information also does not describe masking of laboratory assessors or detailed measurement procedures.

The study population came from a predecessor trial and was restricted to participants who remained on treatment for at least 16 weeks and not more than 40 weeks in that study. This means the extension’s population was defined by continued participation and treatment in the predecessor study; it should not be assumed to represent all adults with asthma or all people who might begin benralizumab treatment. The registry does not report details of who entered the extension among those eligible or reasons for non-entry.

Although the primary endpoint defines an available-value population for laboratory changes, the record does not report the number contributing to that endpoint, the extent or pattern of missing data, or how missing measurements were handled. It also does not report multiplicity procedures despite listing 17 outcome measures, or provide analysis entries. Numerical results for the named secondary outcomes are not reported in the registry record. For safety, the posted counts lack reported exposure-adjusted rates and do not establish event causality. These limitations restrict conclusions to a description of the study design and recorded safety information.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Safety Extension Study With Benralizumab for Asthmatic Adults on Inhaled Corticosteroid Plus Long-acting β2 Agonist — NCT02808819.
• Registry record last updated 2021-04-13; status last verified 2021-03.
• Results first posted 2021-04-13.
• 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

NCT02808819 is the completed Phase 3 MELTEMI study, a multicenter, open-label, non-randomized safety extension of benralizumab in adults with asthma receiving inhaled corticosteroid plus long-acting β2 agonist. It enrolled 447 participants and followed participants continuing from predecessor study D3250C00021 (BORA, NCT02258542). The registered arms used subcutaneous benralizumab every 4 weeks or every 8 weeks.

The primary endpoint was mean change from baseline in basophils, measured in 10^9 cells/L in the full analysis set. The registry lists 17 outcome measures and no analysis entries. Numerical results for the primary endpoint and the named secondary outcomes are not reported in the registry record. Safety reporting includes serious and other adverse-event counts, deaths, and selected serious-event terms. Because the study was non-randomized and the arms are not a like-for-like comparison, the arm counts should be interpreted descriptively rather than as a causal comparison.