This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma (NCT02322775), a randomized phase 3 study. The primary outcome is Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT02322775 |
| Phase | Phase 3 |
| Condition | Asthma |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 211 |
| Arms in the primary outcome | n/a |
| Lead sponsor | AstraZeneca |
| Results posted | Yes |
2. Clinical Question
Population
Adult patients with mild to moderate persistent asthma. The Full Analysis Set included randomized patients who received any investigational product, regardless of protocol adherence or continued participation.
Intervention
Benralizumab 30 mg administered subcutaneously every 4 weeks.
Comparator
Placebo administered subcutaneously every 4 weeks.
Primary question
How did pre-bronchodilator FEV1 change from baseline through Week 12 in the benralizumab group compared with the placebo group?
The primary endpoint is change from baseline in pre-bronchodilator forced expiratory volume in 1 second (FEV1), measured in litres. The stated timeframe includes Baseline, Week 4, Week 8 and Week 12, with the primary comparison focused on change at Week 12. The registry describes the trial’s purpose as confirming benralizumab’s safety and clinical benefit in mild to moderate persistent asthma and understanding its benefit/risk across the spectrum of asthma disease.
The registry identifies this as a randomized, double-blind, parallel-group, placebo-controlled Phase 3 study. Enrollment was 211. It also lists secondary measures that include home morning and evening peak expiratory flow, asthma symptoms, rescue medication use, nocturnal awakenings, ACQ-6, exacerbations, and AQLQ(S)+12 scores. Numerical results for these measures are not reported in the registry record. The primary outcome’s numerical comparison is likewise not reported in the registry record, so the direction and magnitude of the observed difference cannot be described from this record.
3. Trial Design
This was a Phase 3, randomized, double-blind, parallel-group, placebo-controlled study of benralizumab in adults with mild to moderate persistent asthma. AstraZeneca is identified as the sponsor. Enrollment was 211, and the registry status is Completed. The recorded start date is 2015-02-02, and the primary completion date is 2015-10-07.
One group received benralizumab 30 mg subcutaneously every 4 weeks; the other received placebo subcutaneously every 4 weeks. Randomization assigns participants to treatment groups by chance, while double blinding is intended to keep treatment assignment concealed from participants and relevant study personnel. The parallel-group model means the treatment groups are followed as distinct groups rather than participants crossing from one treatment to the other. These are general descriptions of the design terms; further operational details are not reported in the registry record.
The primary measure was change from baseline in pre-bronchodilator FEV1 in litres. The stated assessment schedule includes Baseline, Week 4, Week 8 and Week 12, and the registry describes the Week 12 change as calculated for patients with both baseline and Week 12 measurements. The Full Analysis Set is defined as all randomized patients who received any investigational product, irrespective of protocol adherence and continued participation.
The registry lists 11 outcome measures and 12 analyses. The secondary outcomes cover lung function, asthma symptoms, rescue medication use, nocturnal awakenings, asthma exacerbations and quality of life. The available record does not give a sample-size justification, the allocation ratio, treatment adherence, participant flow, or detailed procedures for randomization and masking. Those details are not reported in the registry record and cannot be inferred from the design label alone.
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: Eligible adult patients were stratified by baseline blood eosinophil count (\<300 cells/μL or ≥300 cells/μL) and by region (USA versus Rest of the World per the IVRS). Patients were then randomized to either benralizumab 30 mg Q4W or placebo in a 1:1 ratio.
Overall Study
| Stage | Benralizumab 30 mg Q4W | Placebo |
|---|---|---|
| STARTED | 106 | 105 |
| COMPLETED | 101 | 99 |
| NOT COMPLETED | 5 | 6 |
Reasons for not completing this period:
| Reason | Benralizumab 30 mg Q4W | Placebo |
|---|---|---|
| Adverse Event | 1 | 0 |
| Lost to Follow-up | 0 | 1 |
| Protocol Violation | 1 | 0 |
| Withdrawal by Subject | 3 | 4 |
| Not willing to perform all FU visits | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set comprised all patients randomised and receiving any investigational product (IP), irrespective of their protocol adherence and continued participation in the study.
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.
| Characteristic | Unit | Benralizumab 30 mg Q4W | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 106 | 105 | 211 | |
| Age, Continuous | Years | 48.3 (SD 14.40) | 51.1 (SD 12.60) | 49.7 (SD 13.58) |
| Age, Customized: >=18-<50 years | Participants | 49 | 44 | 93 |
| Age, Customized: >=50-<65 years | Participants | 43 | 46 | 89 |
| Age, Customized: >=65-<=75 years | Participants | 14 | 15 | 29 |
| Sex: Female, Male: Female | Participants | 62 | 67 | 129 |
| Sex: Female, Male: Male | Participants | 44 | 38 | 82 |
| Race/Ethnicity, Customized: Asian | Participants | 1 | 0 | 1 |
| Race/Ethnicity, Customized: Black or African American | Participants | 7 | 4 | 11 |
| Race/Ethnicity, Customized: White | Participants | 98 | 99 | 197 |
| Race/Ethnicity, Customized: Other | Participants | 0 | 2 | 2 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 6 | 3 | 9 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 100 | 102 | 202 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Pre-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) (L) at Week 12, measured over Baseline, Week 4, Week 8 and Week 12.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Litre |
| Endpoint classification | Continuous Endpoint |
FEV1 is the volume of air a person can forcefully exhale in the first second of a breath, measured in litres. The primary outcome is the change from baseline in pre-bronchodilator FEV1. “Pre-bronchodilator” identifies the timing of the lung-function measurement relative to bronchodilator use; the registry does not provide further measurement procedures.
Change from baseline expresses the Week 12 measurement relative to the participant’s baseline measurement. Comparing change between randomized groups is intended to assess how lung function shifted over the same follow-up period in participants assigned benralizumab and those assigned placebo. FEV1 is a continuous measure, and the registry says the endpoint is summarized as a mean with a standard deviation. General statistical context: a mean describes the central level of a continuous measurement, while a standard deviation describes how spread out individual measurements are around that mean.
The registry specifies assessments at Baseline, Week 4, Week 8 and Week 12, and identifies Week 12 as the primary comparison time. The stated analysis uses a mixed-effect repeated measures approach and adjusts for listed baseline and study factors. However, the registry record does not report group means, the estimated difference between groups, a confidence interval, or a p-value for the primary endpoint. Consequently, this endpoint description explains what was intended to be measured, not the size or precision of an observed treatment contrast.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record specifies a primary endpoint and an analysis method, but does not report a numerical primary-outcome result. It gives no group-specific mean change, between-group estimate, confidence interval, or p-value. Therefore, the magnitude, direction, and statistical precision of the primary comparison are not reported in the registry record. No conclusion about the primary outcome can be drawn from the analysis description alone.
The trial enrolled 211 participants and compared benralizumab 30 mg every 4 weeks with placebo every 4 weeks. Randomization and double blinding are design features intended to support a fair comparison and limit certain sources of bias. They do not replace the need for outcome estimates and their uncertainty. General statistical context: an estimated treatment contrast describes the difference between groups, while a confidence interval conveys the range of values compatible with the data and the analysis assumptions. Neither is reported for the primary comparison in this record.
The primary endpoint is change from baseline in pre-bronchodilator FEV1 at Week 12, with measurements also specified for Week 4 and Week 8. The planned mixed-effect repeated measures analysis includes treatment-by-visit interaction and several baseline or design factors. The registry also notes that Week 12 changes were calculated from patients with both baseline and Week 12 data. These details describe the analytic approach, but they do not reveal how many participants contributed measurements at each visit or how missing observations affected estimates.
Other listed outcomes include morning and evening peak expiratory flow, asthma symptom score, rescue medication use, nocturnal awakenings, ACQ-6, asthma exacerbations and AQLQ(S)+12. The registry lists 11 outcome measures and 12 analyses, but numerical results for these measures are not reported in the registry record. Their presence in the outcome list should not be mistaken for evidence about their observed values or treatment-group comparisons.
The safety data list 2 serious adverse events in each group among 106 participants at risk in the benralizumab group and 105 in the placebo group. Other adverse event counts are also listed, but the registry does not provide enough detail to establish event timing, severity beyond the serious classification, or whether affected participants experienced more than one event. Deaths are not reported in the registry record. These figures describe recorded counts and should not be treated as a complete account of safety without the relevant definitions and fuller results.
The registry’s trial status is Completed, but completion does not itself establish the outcome of the primary comparison. The reported analysis plan and outcome definitions permit readers to understand what the investigators intended to estimate. Without the estimate and its uncertainty, the treatment effect remains undetermined from this record.
9. Statistical Methods Explained
The primary endpoint is continuous: change from baseline in pre-bronchodilator FEV1, measured in litres. The registry reports the outcome parameter as a mean and the dispersion measure as a standard deviation. General statistical context: continuous measurements can vary across participants, so a group mean provides a concise description of the average while the standard deviation describes individual-level spread. The registry does not report the actual means or standard deviations for the primary endpoint.
What does the repeated-measures model do?
The stated method is a mixed-effect repeated measures analysis (MMRM). General statistical context: repeated-measures models are designed for outcomes measured at multiple visits on the same participants. They account for the fact that observations from one participant over time are related, rather than treating every visit measurement as independent. The precise covariance structure, estimation details, and any model diagnostics are not reported in the registry record.
The protocol-specified visits in the primary description are Week 4, Week 8 and Week 12, with baseline information also included. The model lists visit and a treatment-by-visit interaction as fixed effects. General statistical context: a treatment-by-visit interaction allows the estimated contrast between treatment groups to vary across visits. The primary clinical question is focused on Week 12, even though measurements across visits contribute to the repeated-measures framework.
Which factors enter the stated model?
The registry lists baseline blood eosinophil count category (≥300 cells/μL or <300 cells/μL), protocol-specified visit, region (Europe or North America), and treatment-by-visit interaction as fixed effects. Baseline pre-bronchodilator FEV1 is included as a covariate. General statistical context: adjustment for baseline measurements and prespecified factors can account for differences in those characteristics when estimating treatment contrasts. The registry does not report the fitted coefficients or the results within the listed eosinophil or regional categories.
A covariate is a variable included in a statistical model alongside the treatment and outcome. Here, baseline pre-bronchodilator FEV1 is the specified covariate. The stated model also incorporates baseline blood eosinophil category and region. The description does not report other potential adjustment variables, nor does it indicate whether any additional analyses were conducted.
What does a confidence interval communicate?
General statistical context: a confidence interval expresses uncertainty around an estimated effect, conditional on the statistical model and its assumptions. A narrower interval indicates greater precision than a wider interval, while an interval spanning values on both sides of no difference may be compatible with more than one interpretation. These are general principles, not findings from this trial. A primary-outcome confidence interval is not reported in the registry record, so the precision of the treatment contrast cannot be assessed.
General statistical context: over-dispersion matters when observed variability is greater than a model’s assumptions allow. If variability is understated, uncertainty estimates may be too small; if it is adequately represented, estimates of precision are more credible. The registry identifies a continuous outcome and a standard deviation, but does not report an over-dispersion assessment or any alternative variance model. No claim about over-dispersion in this trial is possible from the record.
What is known about the analysis population?
The Full Analysis Set comprised all randomized patients who received any investigational product, irrespective of protocol adherence or continued participation. This definition describes who was eligible for that analysis population; it does not report the actual number analyzed for the primary outcome. The registry also states that Week 12 changes were calculated based on patients with both baseline and Week 12 data. The number of participants meeting that measurement requirement is not reported in the registry record.
General statistical context: missing measurements can reduce the information available for a longitudinal analysis, and the impact depends in part on why data are missing and on the analysis assumptions. MMRM methods can use available repeated measurements under specified assumptions, but the registry does not give enough detail to identify the missing-data assumptions or procedures used in this trial. It does not report reasons for missing measurements, imputation procedures, or sensitivity analyses.
How should planning illustrations be understood?
General statistical context: sample-size planning illustrations explore how many participants might be needed under stated assumptions to detect an effect of a chosen size. They are not observed results, and they do not state the probability that this completed trial found a true effect. The planning assumptions described for this record use a two-sided significance level of 0.05, equal allocation, a normal approximation, and effects expressed as fractions of an observed effect. For time-to-event outcomes, the stated planning convention is total events; for other outcomes, it is participants per arm. The registry does not report a sample-size justification for the trial itself. Any planning illustrations should therefore be read as calculations based on the posted effect and assumptions, not as the trial’s original design rationale or as observed power.
The record does not report an interim-analysis plan, stopping rules, multiplicity adjustment, or a detailed statistical analysis plan beyond the primary model description. Those matters are not reported in the registry record. This limits the ability to evaluate how the analysis was governed or how multiple outcomes and analyses were handled.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 11 outcome measures and 12 analyses. Multiple outcomes and analyses raise a general statistical issue: when many hypotheses are assessed, the chance of at least one apparently unusual result can increase if each is interpreted separately without accounting for multiplicity. Whether and how a study controls that issue depends on its prespecified testing strategy. No multiplicity adjustment or testing hierarchy is reported in the registry record, so it is not possible to determine whether the reported analyses were intended to support confirmatory claims or were treated as exploratory.
The primary outcome description specifies MMRM for change from baseline in pre-bronchodilator FEV1, with measures at Week 4, Week 8 and Week 12. It also states that Week 12 changes were calculated based on patients with both baseline and Week 12 measurements. This establishes a measurement requirement for the Week 12 change, but does not report how many participants had the required data or the extent of missingness at each visit.
The Full Analysis Set is defined as randomized participants who received any investigational product, regardless of adherence or continued participation. The actual primary analysis count is not reported in the registry record. The record does not describe missing-data assumptions, imputation methods, sensitivity analyses, or reasons for missing measurements. General statistical context: missingness can affect both the amount of information and the interpretation of an estimate, particularly if the chance of a missing observation is related to participant characteristics or outcomes. Without the analysis details and participant-level flow, the potential impact cannot be assessed.
The sample-size planning description is an illustration based on the observed effect and specified assumptions, rather than a reported justification for the trial’s original enrollment. No interim analyses or related adjustment procedures are reported in the registry record. The available information therefore supports describing the stated model and analysis population, but not a full assessment of multiplicity control or missing-data handling.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Benralizumab 30 mg Q4W | 2 | 106 | 1.9% |
| Placebo | 2 | 105 | 1.9% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 3% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Benralizumab 30 mg Q4W | 19 of 106 |
| Placebo | 14 of 105 |
Most frequent serious adverse event terms
| Event term | Organ system | Benralizumab 30 mg Q4W | Placebo |
|---|---|---|---|
| Pancytopenia | Blood and lymphatic system disorders | 1 of 106 | 0 of 105 |
| Cervix carcinoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 106 | 1 of 105 |
| Colon adenoma | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | 0 of 106 | 1 of 105 |
| Suicide attempt | Psychiatric disorders | 1 of 106 | 0 of 105 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Benralizumab 30 mg Q4W | Placebo |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 8 of 106 | 8 of 105 |
| Upper respiratory tract infection | Infections and infestations | 5 of 106 | 5 of 105 |
| Asthma | Respiratory, thoracic and mediastinal disorders | 4 of 106 | 3 of 105 |
| Headache | Nervous system disorders | 4 of 106 | 1 of 105 |
Serious events with the highest arm-level rate: cervix carcinoma (1.0%), colon adenoma (1.0%), pancytopenia (0.9%), suicide attempt (0.9%).
The serious adverse event figures list 2 events in the benralizumab 30 mg Q4W group among 106 participants at risk, and 2 in the placebo group among 105 participants at risk. These are the registry’s posted counts. They should be read as event counts in the listed groups, not automatically as counts of distinct participants: the record does not specify whether a participant could contribute more than one event.
The record also lists 19 other adverse events among 106 participants at risk in the benralizumab group and 14 among 105 participants at risk in the placebo group. The available description does not define the “other” category in further detail, so these counts should not be combined with the serious-event counts or treated as a single severity category without additional information.
Several serious-event terms are listed with percentages: Cervix carcinoma and Colon adenoma at 1.0% each, and Pancytopenia and Suicide attempt at 0.9% each. The record does not identify the denominator or clarify whether these terms represent unique participants or events. Deaths are not reported in the registry record; that is different from a report of no deaths. These data are a limited description of the posted safety figures, not a complete assessment of event timing, relatedness, severity, or overall safety.
12. What the Result Does, and Does Not, Mean
The registry record describes a randomized comparison of benralizumab and placebo, identifies the primary lung-function endpoint, and specifies a repeated-measures analysis. It does not report the primary endpoint’s numerical results. Accordingly, the record does not establish the size, direction, or precision of the Week 12 treatment contrast. It also does not support a conclusion about whether a difference was statistically significant.
The result would need to be interpreted using an estimated between-group contrast and its uncertainty, together with the outcome definition and analysis population. General statistical context: statistical evidence and clinical relevance are different questions. A precise estimate may still require clinical context, while an imprecise estimate can leave a wide range of effects compatible with the data. In this record, the estimate and its uncertainty are not reported, so neither dimension can be evaluated for the primary endpoint.
The outcome schedule includes Baseline, Week 4, Week 8 and Week 12. The planned model accounts for repeated measurements and includes specified baseline and study factors, but the description does not report the model output. Listing an outcome, a visit, or an analysis method is not equivalent to reporting an outcome result.
The safety figures provide counts for serious and other adverse events and list several serious-event terms. They do not establish the full safety profile because event definitions, participant-level counts, timing, relatedness, and death data are not reported. The registry’s Completed status confirms the study status recorded there, but does not by itself indicate what the outcome comparison showed.
Secondary measures address lung function, symptoms, medication use, nocturnal awakenings, exacerbations, and quality of life. Their numerical results are not reported in the registry record. The evidence that can be described is therefore about the trial’s design, outcome definitions, analysis plan, and limited safety counts—not the magnitude of its efficacy results or a comprehensive benefit/risk conclusion.
13. Why This Trial Matters Statistically
This trial illustrates why an outcome definition and an analysis plan are not substitutes for numerical results. The registry identifies a clinically interpretable continuous endpoint—change from baseline in pre-bronchodilator FEV1—and specifies the Week 12 comparison. It also describes an MMRM analysis that uses repeated measurements across visits and adjusts for listed factors. These details help readers understand the intended estimand and model structure, even though the estimated contrast is not reported.
The design combines randomization, double blinding, parallel groups and placebo control. General statistical context: these design features can help structure a comparison and limit some biases, but they cannot show how large or precise an observed effect was. For interpretation, readers need group results, a between-group estimate and an uncertainty measure, as well as information about the number analyzed and missing data. Those results and details are not reported in the registry record.
The record also illustrates the distinction between trial planning and observed evidence. Its sample-size description concerns planning illustrations computed from an observed effect under stated assumptions; it is not identified as the original study’s design justification. Such calculations can explore planning scenarios, but should not be mistaken for observed power or a result of the randomized comparison. The trial’s own sample-size justification is not reported in the registry record.
Finally, the registry lists multiple outcome measures and analyses, yet does not report a multiplicity strategy. That omission matters for assessing how a set of results would be interpreted if reported. Overall, the record permits a clear account of the intended primary question and the method named for addressing it, while leaving the effect estimate, precision, missing-data impact and multiplicity handling unresolved.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The principal limitation for interpreting the trial’s efficacy is that numerical outcome results are not reported in the registry record. There is no primary between-group estimate, group-specific mean change, confidence interval, or p-value. Numerical results for the listed secondary outcomes are also not reported. The study design and analysis description therefore cannot establish the observed treatment effect.
The record does not report the number of participants included in the primary analysis or the number with measurements at each visit. Although the Full Analysis Set is defined and Week 12 change is described as based on patients with both baseline and Week 12 data, participant flow and missing-data procedures are not reported. The effects of missing measurements on the estimate cannot be evaluated.
Further statistical details are absent, including the model covariance structure, diagnostic checks, multiplicity strategy, interim analyses, and sensitivity analyses. These are not reported in the registry record. The protocol’s sample-size justification is also not reported; the planning description is an illustration based on the observed effect and specified assumptions.
The safety information is limited to counts and selected event terms. Definitions and denominators for the listed serious-event percentages are not clear in the record, and it does not specify whether counts refer to events or unique participants. Deaths are not reported in the registry record. These gaps prevent a comprehensive interpretation of the safety figures.
The record gives the trial population, interventions, design labels, and endpoint but does not provide additional details about eligibility criteria, treatment adherence, allocation procedures, or the conduct of masking. Those features should not be inferred beyond what is explicitly recorded. These limitations concern what can be evaluated from the registry record and do not establish that unreported analyses or procedures were absent from the full study documentation.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study to Evaluate the Efficacy and Safety of Benralizumab in Adult Patients With Mild to Moderate Persistent Asthma — NCT02322775.
- Registry record last updated 2017-08-15; status last verified 2017-08.
- Results first posted 2017-02-14.
- 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.
Continue through the Clinical Biostats statistical pathway
Use this trial's endpoint as a starting point for deeper study of effect measures, confidence intervals, and sample-size planning.
18. Record Summary
NCT02322775 is a completed Phase 3 randomized, double-blind, parallel-group, placebo-controlled trial sponsored by AstraZeneca. It enrolled 211 adults with mild to moderate persistent asthma. Benralizumab 30 mg was administered subcutaneously every 4 weeks, with placebo administered on the same schedule in the comparison group.
The primary endpoint was change from baseline in pre-bronchodilator FEV1 at Week 12, assessed within a stated repeated-measures analysis that included Week 4 and Week 8 visits. The registry defines the Full Analysis Set and lists secondary measures covering lung function, symptoms, rescue medication use, nocturnal awakenings, exacerbations and quality of life.
Numerical primary and secondary outcome comparisons are not reported in the registry record. Serious adverse event counts are listed as 2 in each group; deaths are not reported. The record does not report multiplicity control, missing-data procedures, or the trial’s sample-size justification.