A Phase 2a Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Adults With Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2a Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Adults With Asthma (NCT00783289), a randomized phase 2 study. The primary outcome is Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs).

2. Clinical Question

The registry describes a safety and tolerability study, not an efficacy trial. Its primary outcome counts participants with treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (TESAEs). A TEAE was an event absent before treatment or one that worsened relative to the participant’s pretreatment state, arising between the first study-drug dose and up to Day 161. An adverse event was defined as an untoward medical occurrence in a participant who received study drug, whether or not it was considered related to treatment.

The registry lists placebo and three benralizumab dose groups. The question is therefore about reported event counts across those groups during the stated observation period. It does not establish, by itself, whether an event was caused by the study drug. The registry’s definition of a serious adverse event includes specified severe outcomes or an event deemed significant for another reason.

The safety population included participants who received at least one dose of investigational product. The registry does not report an efficacy endpoint in the registry record for this analysis. It also does not report a single statistical comparison that combines the dose groups into one treatment-versus-placebo estimate.

3. Trial Design

This was a randomized, double-blind, parallel-group Phase 2a study in adults with asthma. It compared placebo with subcutaneous benralizumab administered at 25 mg, 100 mg, or 200 mg. The registry reports an enrollment of 35 and identifies MedImmune LLC as the sponsor. The study is marked completed, with a start date of 2008-11-14 and a primary completion date of 2009-11-17.

The intervention descriptions specify injections on Day 0, Day 28, and Day 56 for placebo and each benralizumab dose. The study is described as dose-escalation, but the registry record does not report the detailed operational rules for dose escalation or how randomization assigned participants to groups. It identifies the allocation as randomized, the masking as double, and the model as parallel.

The primary objective was to evaluate safety and tolerability of escalating multiple subcutaneous doses of MEDI-563, the study name for benralizumab. The primary outcome was the number of participants reporting TEAEs and TESAEs from Day 0 to Day 161. The safety population was defined as participants who received at least one dose of investigational product.

Secondary outcomes listed in the registry include benralizumab pharmacokinetic measures: time to maximum observed serum concentration, maximum observed serum concentration, area under the curve from time zero to infinity, and terminal-phase elimination half-life. The registry also lists the number of participants exhibiting anti-drug antibodies at any visit. The record does not report results for those secondary outcomes in the registry record for this analysis.

The registry record does not report the planned sample-size justification, the statistical analysis plan, or participant flow by randomized group. Those omissions limit the ability to assess how the study was designed to support comparisons among dose groups. Randomization and masking describe important design features, but they do not on their own establish the precision or interpretation of the reported event counts.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety population included all participants who received at least 1 dose of the investigational product.

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: Intent-to-treat (ITT) population included all participants randomized into the study.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Treatment-Emergent Serious Adverse Events (TESAEs), measured over Day 0 to Day 161.

The primary endpoint counts participants reporting treatment-emergent adverse events and treatment-emergent serious adverse events during the period from Day 0 to Day 161. It is a safety endpoint expressed as participant counts, rather than a measure of symptom improvement or clinical benefit. The registry defines a TEAE as an event that was absent before treatment or worsened relative to the pretreatment state, with treatment-emergent status based on when the event occurred.

The registry defines an adverse event broadly as an untoward medical occurrence in a participant who received study drug, without regard to whether a causal relationship was considered possible. Seriousness is determined by specified outcomes or by whether the event is otherwise deemed significant. These definitions distinguish event occurrence and seriousness from an investigator’s judgment about drug causality.

Counting participants with events is a direct way to report how many people in each safety group experienced an event. It is useful in a safety-focused study because it describes the observed burden of reported events over the stated follow-up period. However, a count does not describe event duration, severity beyond the serious/non-serious classification, recurrence, or the time at which an event occurred. The registry’s primary outcome does not provide those details in the registry record for this analysis.

The endpoint is relevant to safety and tolerability, but it does not answer whether benralizumab changes asthma outcomes. Nor does a count alone establish that treatment caused an event. Interpretation requires attention to the group denominators, the limited number of observations, the event definitions, and the lack of a reported inferential comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The study’s design and outcome type determine what can be learned from its reported results. It was randomized, double-blind, and parallel-group. Randomization is generally used to reduce systematic differences between groups at assignment, while masking is generally intended to limit the influence of treatment knowledge on care or assessment. These design features are relevant context, but they do not replace examination of the outcome definitions, the observed counts, or the statistical analyses actually reported.

What kind of endpoint is this?

The primary endpoint is a participant count for treatment-emergent adverse events and treatment-emergent serious adverse events. In general, a binary outcome records whether a participant experienced an event or did not experience it during the defined period. A group count is the number of participants recorded as having the event; a denominator indicates the participants at risk or assessed in that group. Here, the registry lists group-specific counts and at-risk denominators, but does not report an inferential comparison for the primary endpoint.

The count does not capture all aspects of an event. A participant count does not indicate how many episodes occurred, how long an episode lasted, or when it started. The registry gives a definition of seriousness and a treatment-emergent time window, but the registry entries available do not include event-level timing or a breakdown by specific non-serious event term. The list of top serious-event terms is empty, and individual serious-event terms are not reported in the registry record.

How should group comparisons be understood?

In general, comparing groups on a binary outcome can involve a difference in proportions, a ratio of proportions, or a statistical test. Each approach answers a somewhat different question and depends on the chosen analysis population and assumptions. A confidence interval can communicate the range of values compatible with the observed data under a specified method. These are general statistical concepts, not methods claimed to have been used for this study.

The registry record does not report an effect estimate, confidence interval, p-value, or a model for the primary safety outcome. It lists no analyses. The endpoint is also described in more than one category, and the record does not reduce it to one comparison. Consequently, the event counts can be described, but there is no reported estimate with which to quantify a treatment-versus-placebo contrast or its precision.

Small or sparse counts require particular care. In general, when events are uncommon or group sizes are limited, statistical estimates can be unstable and uncertainty can be wide. A zero observed count does not mean the underlying event probability is exactly zero; it means no event was recorded in the observed participants during the specified period. This general principle does not supply an unreported probability or interval for this trial.

What do the outcome definitions establish?

The registry defines TEAEs by both timing and comparison with the pretreatment state: an event must arise after the first dose within the stated window and be absent before treatment or have worsened relative to the pretreatment condition. The record defines adverse events without regard to the possibility of a causal relationship. Thus, treatment-emergent status describes when an event occurred and how it related to baseline status; it is not itself evidence that the drug caused the event.

Seriousness is a separate classification. The definition includes death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, congenital anomaly, or another event deemed significant. The serious-event counts therefore concern a defined subset of safety outcomes. No deaths are reported as numeric results in the registry entries; the death fields are not reported in the registry record.

What can be said about statistical planning?

The registry record does not report a statistical analysis plan, a sample-size justification, planned interim analyses, or the methods used to handle multiplicity. These details matter because they establish which comparisons were planned, how uncertainty was to be quantified, and how conclusions were to be controlled when multiple outcomes or dose comparisons are examined. Their absence means those choices cannot be evaluated from the registry record.

In general, multiplicity arises when researchers assess several outcomes or make several comparisons. Testing many questions can increase the chance of a misleading positive result if no suitable approach is specified. This study lists placebo and multiple dose groups and several secondary outcomes, but the record does not say how any multiplicity was handled. It would be inappropriate to assume a correction method or a prespecified testing sequence.

Any sample-size calculation is a planning illustration, not observed power. The registry’s stated planning assumptions describe an illustration based on an observed effect, equal allocation between two arms, a two-sided significance level of 0.05, and a normal approximation. The primary outcome, however, is not reduced in the registry record to a single comparison, and no analysis result is listed. A planning illustration cannot substitute for a reported estimate and its uncertainty, nor establish what the study was capable of detecting in practice.

What is unknown about missing data and analysis populations?

The primary outcome specifies a safety population of participants who received at least one dose. The record does not report participant flow from enrollment through treatment, missing outcome status, reasons for missingness, or any imputation or sensitivity method. General statistical practice distinguishes the intended analysis population from the observations actually available for a particular endpoint; without the relevant flow and missing-data details, the completeness of the safety outcome cannot be assessed.

The listed safety denominators are the appropriate context for reading the group counts in this record. They do not reveal why a participant might be absent from a particular denominator. The record also does not report whether analyses were adjusted for baseline characteristics or other factors. No such adjustment should be inferred from the randomized design alone.

10. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary safety outcome with TEAE and TESAE categories, several benralizumab dose groups, and secondary pharmacokinetic and antibody outcomes. It does not report a statistical analysis plan, a prespecified testing sequence, or a method for controlling multiplicity. In general, multiplicity matters when several outcomes or comparisons are considered, because the interpretation of isolated statistical tests can be affected by how many questions are examined. No particular multiplicity approach can be attributed to this study from the registry record.

The record does not report an inferential analysis for the primary outcome. It provides descriptive participant counts and denominators, but no effect estimate, confidence interval, or p-value. It also does not state whether any subgroup, adjusted, or sensitivity analyses were planned or performed. The registry’s description of planning assumptions is not a substitute for analysis results and does not establish observed power.

The safety population included participants who received at least one dose of investigational product. Participant flow, endpoint-specific missingness, reasons for missing data, and methods for handling missing outcomes are not reported in the registry record. It is therefore not possible to assess whether missingness affected the results or whether any imputation was used. Randomization describes assignment to groups; it does not answer these questions about outcome availability or analytic handling.

The registry lists secondary outcomes for pharmacokinetics and anti-drug antibodies, but the registry entries available for this analysis do not report their results. It would be speculative to infer whether those outcomes were analyzed, how multiplicity across them was addressed, or how missing observations were handled.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 0% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports zero treatment-emergent serious adverse events among 6 placebo participants, among 7 participants receiving benralizumab 25 mg, among 6 receiving benralizumab 100 mg, and among 6 receiving benralizumab 200 mg. These are observed counts within the safety population and the stated follow-up period, Day 0 to Day 161. They do not show that serious events are impossible, nor do they establish equal safety across groups.

The other adverse-event counts are 3 among 6 for placebo, 4 among 7 for benralizumab 25 mg, 4 among 6 for benralizumab 100 mg, and 4 among 6 for benralizumab 200 mg. The record does not provide event terms for these counts in the registry record for this analysis, so their clinical nature cannot be characterized further. The serious-event terms list is empty.

Counts depend on the group denominator and the period and definitions used. In general, a small number of observed participants gives limited precision about event frequency in a wider population. No confidence intervals or comparative statistical tests are reported. The registry also does not report numeric death results; the death fields are not reported in the registry record.

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

The results describe recorded safety events among participants in a randomized, double-blind, placebo-controlled study of multiple-dose subcutaneous benralizumab in adults with asthma. The primary endpoint counts participants with treatment-emergent adverse events and serious adverse events over the period from Day 0 to Day 161. The reported group counts show that no treatment-emergent serious adverse events were recorded in the listed groups, while other adverse-event counts were recorded in each group.

These observations are useful as a description of what was recorded in this study. They should not be interpreted as proof that benralizumab caused or prevented any event. The registry definition of an adverse event does not require a possible causal relationship to treatment, and no causal analysis is reported. Similarly, the absence of recorded serious events in these groups does not establish that the risk is absent or identical across groups.

The registry does not report a single inferential comparison for the primary outcome, and it gives no effect estimate, confidence interval, or p-value. As a result, the counts do not establish statistical significance, equivalence, or a dose-response relationship. The group denominators are limited, and the record does not provide enough detail about missing outcomes or participant flow to evaluate completeness beyond the stated safety-population definition.

The study’s primary objective was safety and tolerability. The registry entries available for this analysis do not report an efficacy result for asthma. Therefore, these safety observations do not answer whether treatment changes asthma symptoms, exacerbations, or other disease outcomes. Nor do they support treatment recommendations. They are descriptive findings from the recorded study population and follow-up period, with important uncertainty about how well they generalize beyond that study.

The record also identifies secondary pharmacokinetic and anti-drug antibody outcomes, but does not report their results in the registry record. The interpretation should remain bounded by the endpoints and data actually recorded: observed safety counts, their group denominators, and the stated event definitions.

13. Why This Trial Matters Statistically

This study illustrates a common statistical challenge in early-phase safety research: event counts can be central to the clinical question even when the study is not designed or reported as a definitive comparative test. The registry identifies a safety-focused objective and describes TEAEs and TESAEs over a defined period. Presenting the counts alongside their group denominators helps readers understand what was observed without turning sparse data into a stronger conclusion than they support.

The distinction between an event and an event caused by treatment is especially important. The registry defines an adverse event without regard to whether a causal relationship is possible. Treatment-emergent status is based on timing and change from pretreatment status; it does not, by itself, establish causation. Seriousness is another separate classification, based on the listed outcomes or an event deemed significant.

The registry also shows why design labels and outcome evidence must be considered together. Randomization and double masking are relevant safeguards, but they do not supply the missing effect estimate, uncertainty interval, analysis plan, or participant-flow details. Without a reported inferential comparison, the group counts remain descriptive. A zero serious-event count is meaningful as an observation, but not as proof of zero underlying risk.

Finally, this record highlights the value of transparent reporting beyond headline outcomes. The registry lists pharmacokinetic and antibody outcomes, while the registry entries do not include their results. Statistical interpretation depends not only on design and observed counts, but also on clear reporting of analysis populations, missingness, planned comparisons, and uncertainty. Those elements determine how far readers can responsibly extend a study’s descriptive findings.

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 primary limitation for interpreting the posted results is that the registry record does not report a statistical analysis for the primary outcome. Group counts are available, but no effect estimate, confidence interval, p-value, or comparative model is reported. The endpoint includes TEAE and TESAE categories and is not reduced in the registry record to a single comparison.

The listed safety group denominators are limited, and serious events were not observed in the recorded groups. Sparse event data provide limited precision about the frequency of uncommon outcomes. The counts also do not describe event duration, recurrence, timing within follow-up, or detailed non-serious event terms in the registry record for this analysis. The serious-event terms list is empty.

The record states that enrollment was 35 and defines the safety population as participants who received at least one dose. It does not report participant flow, reasons for any differences between enrollment and the listed at-risk denominators, or endpoint-specific missingness. It also does not describe how missing outcomes were handled. These gaps prevent an assessment of the completeness and potential impact of missing safety information.

The statistical analysis plan, sample-size justification, planned interim analyses, multiplicity strategy, and any adjusted analyses are not reported in the registry record. The registry entries available also do not report results for the listed pharmacokinetic or anti-drug antibody outcomes. These omissions limit assessment of the intended analysis and the full set of study findings.

The findings are confined to the studied adults with asthma, the listed dose groups, the specified administration schedule, and the Day 0 to Day 161 safety window. They should not be generalized beyond the record without evidence addressing the differences in population, treatment, and follow-up.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Phase 2a Study to Evaluate the Safety and Tolerability of Benralizumab (MEDI-563) in Adults With Asthma — NCT00783289.
• Registry record last updated 2019-12-27; status last verified 2019-12.
• Results first posted 2019-12-27.
• 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.

18. Record Summary

NCT00783289 is a completed randomized, double-blind, parallel-group Phase 2a study of subcutaneous benralizumab in adults with asthma. The registry reports enrollment of 35 and identifies MedImmune LLC as sponsor. Study dates are 2008-11-14 to 2009-11-17 for start and primary completion.

Placebo and benralizumab at 25 mg, 100 mg, or 200 mg were administered on Day 0, Day 28, and Day 56. The primary safety outcome counted participants reporting TEAEs and TESAEs from Day 0 to Day 161. The registry reports no serious events in the listed safety groups and reports other adverse-event counts of 3, 4, 4, and 4 for placebo, 25 mg, 100 mg, and 200 mg, respectively.

No inferential analysis, confidence interval, p-value, or participant-flow account is reported in the registry record. Secondary outcomes are listed for pharmacokinetics and anti-drug antibodies, but their results are not reported in the registry record for this analysis.