Efficacy and Safety of Benralizumab in Patients With Non-cystic Fibrosis Bronchiectasis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of Benralizumab in Patients With Non-cystic Fibrosis Bronchiectasis (NCT05006573), a randomized phase 3 study. The primary outcome is Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period.

2. Clinical Question

The study was designed to test whether benralizumab would reduce exacerbation rates relative to placebo in this population. The primary endpoint is a rate, so it reflects exacerbations relative to time under observation rather than simply the number of participants who experienced an exacerbation. The posted primary comparison is between the benralizumab and placebo groups in the Full Analysis Set.

The registry also describes an open-label extension for eligible participants who completed the double-blind treatment period on investigational product. In that extension, all participants received benralizumab. The open-label period therefore addresses a different treatment setting from the blinded placebo comparison and does not provide a continuing randomized comparison between the original groups.

3. Trial Design

This was a multicentre, randomized, double-blind, parallel-group, placebo-controlled phase III study. The registry lists triple masking. Participants were assigned to benralizumab 30 mg or matching placebo, both administered subcutaneously, with standard-of-care therapy. The registry enrollment is 100. The primary results include 54 participants in the benralizumab group and 45 in the placebo group.

The planned double-blind treatment period could last from 28 to 52 weeks, depending on the timing of randomization and when a revised study protocol became effective. The primary endpoint was measured through the end of that period. This variable follow-up window matters for interpretation: the annualized rate expresses events relative to exposure time, while the amount of observation available for an individual could vary.

Participants completing the double-blind period on investigational product could be eligible for an open-label extension. The revised extension was intended to allow approximately 32 weeks of open-label benralizumab treatment: 24 weeks followed by a follow-up visit 8 weeks after the last dose. In the posted extension groups, 38 participants are listed for benralizumab and 40 for placebo switched to benralizumab. Because both groups received benralizumab in the extension, those data do not retain the original placebo-controlled comparison.

The registry lists the study as terminated, with a start date of 2021-07-21 and a primary completion date of 2024-04-16. The reason for termination and whether the study ended as originally intended are not reported in the registry record. The original study-specific sample-size assumptions, planned interim analyses, and detailed statistical plan are also not reported in 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: All patients completed a screening period of 2 to 6 weeks during which inclusion/exclusion criteria was assessed, disease activity, lung function and patient reported outcomes (PROs) were recorded, medical history and clinical laboratory were taken.

Double-blind Treatment Period

Reasons for not completing this period:

Open-label Extension Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set: All patients randomized and receiving at least one (1) dose of Investigational Product are included in the full analysis set, 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.

Population: All participants who were randomized and received any Investigational Product were included in the full analysis set.

6. Primary Endpoint

The registry lists the primary outcome as Annualized Bronchiectasis Exacerbations Rate in the Double-blind Period, measured over through Double-blind period, at least 28 weeks and up to 52 weeks.

The primary endpoint is the annualized rate of non-cystic fibrosis bronchiectasis exacerbations during the double-blind treatment period. The registry describes the endpoint as a least-squares mean, with results expressed in exacerbations per year and uncertainty reported as a 95% confidence interval. The Full Analysis Set includes randomized participants who received at least one dose of investigational product, irrespective of protocol adherence or continued participation.

An event rate is used when the amount of time participants are observed can differ. Rather than comparing only the number of events, an annualized rate relates events to exposure time. That makes it possible to summarize event frequency over follow-up periods that were at least 28 weeks and up to 52 weeks. It does not mean that every participant was observed for a full year; the rate is expressed on an annual scale.

Exacerbations are clinically relevant events for the condition being studied, and the trial was designed around whether their rate differed between the randomized groups. A rate endpoint can account for repeated events, unlike an endpoint that records only whether a participant had any event. The registry’s result is a group-level estimate, however, and does not describe the experience of every participant. Its interpretation depends on the model and the uncertainty around the estimated comparison.

7. Results Posted in the Registry

• Benralizumab 30 mg: 1.44 versus 1.27 (exacerbations per year) on control; rate ratio 1.13 (95% CI 0.71–1.82, derived from the posted confidence limits); p ≈ 0.602.

8. Secondary Efficacy Endpoints

The registry also posts results for secondary outcomes. For each outcome below, the endpoint type, the test applied to the posted summary statistics, the result and its interpretation are given in turn. Secondary endpoints are usually not adjusted for multiple testing, so they support rather than confirm the primary finding.

Time to First Exacerbation in the Double-blind Treatment Period

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Regression, Cox); it was not recalculated.
• Result:
  • Benralizumab 30 mg vs Placebo: hazard ratio 1.12 (95% CI 0.67–1.91), reported p = 0.668 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval includes no difference (a ratio of 1), so these data do not show a statistically significant difference between Benralizumab 30 mg vs Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The registry lists 12 posted secondary outcomes. They cover time to first exacerbation, respiratory symptoms and quality-of-life measures, lung function, and other quality-of-life scales. The posted numerical secondary comparison described in detail is time to first exacerbation; numerical results for the other listed measures are not reported in the registry record.

For time to first exacerbation, the registry reports a hazard ratio of 1.12, with a 95% confidence interval from 0.67 to 1.91 and p = 0.668. This result is not a second measurement of the primary endpoint: it considers the timing of the first event, while the primary endpoint concerns the annualized rate of exacerbations. Its estimate and uncertainty do not establish a clear difference between the groups. The remaining secondary outcomes cannot be used to claim a consistent or inconsistent pattern because their comparative numerical results are not reported in the registry record.

Secondary outcomes can add context by examining different aspects of the condition and treatment period, but their interpretation depends on the analysis plan, completeness of outcome reporting, and control of multiplicity. When many outcomes are examined, the chance of at least one apparently unusual result can increase if each is assessed separately without adjustment. Whether multiplicity was controlled, and how any outcome hierarchy was specified, are not reported in the registry record. Accordingly, unadjusted secondary results carry less weight than a prespecified primary result and should be treated as supportive or exploratory rather than as independent confirmation.

The secondary findings should be considered alongside, not substituted for, the primary comparison. In this record, the primary estimate itself is imprecise, and the available secondary comparison is also imprecise. The broader set of listed endpoints does not supply enough reported numerical evidence to characterize an overall pattern across symptoms, lung function, and quality of life.

Secondary outcomes registered for this trial, for reference (only those above were recalculated):

• Time to First Exacerbation in the Double-blind Treatment Period
• Change From Baseline in QoL-B-RSS Over the Double-blind Period
• Change From Baseline in Pre-dose Pre-BD FEV1 Over the Double-blind Treatment Period
• Change From Baseline in LCQ Total Score Over the Double-blind Period
• Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Physical Functioning Scale
• Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Role Functioning Scale
• Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Emotional Functioning Scale
• Change From Baseline in QoL-B Scales (Excluding QoL-B-RSS) Over the Double-blind Period: Social Functioning Scale

9. Statistical Interpretation

10. Statistical Methods Explained

The primary endpoint is an event rate, measured in exacerbations per year. An event-rate analysis is useful when participants contribute different amounts of observation time or can experience more than one event. General explanation: an event count alone can be misleading if one group has more time under observation, because more observed time creates more opportunity for events. A rate puts the count in relation to time at risk. Annualization expresses that rate on a common time scale but does not imply that all participants were followed for the same duration.

Why use a negative binomial model?

The registry identifies a negative binomial model for the sponsor’s primary comparison. General explanation: count outcomes often vary more across participants than a simple Poisson model expects. This extra variability is called over-dispersion. A negative binomial model can allow for over-dispersion when estimating event rates and comparing groups. The registry record does not report the model’s covariates, any exposure-time offset details, or other implementation choices, so those should not be inferred.

The sponsor reports the comparison as a risk ratio, with an estimate of 1.14 and a 95% confidence interval from 0.71 to 1.82. For a rate ratio, the reference value for no difference is 1. A value above 1 indicates a higher estimated rate in the first named group relative to the comparison group; a value below 1 indicates a lower estimated rate. The point estimate is not a certainty about the underlying effect. Its interval communicates how uncertain the estimate remains under the analysis.

What does a confidence interval describe?

General explanation: a confidence interval is a range of estimates compatible with the observed data under the statistical model and its assumptions. It is not a range containing a fixed proportion of individual participants’ outcomes, nor does it assign a probability to the true effect being inside the particular interval. A wider interval indicates less precision than a narrower interval on the same scale. For the primary comparison, the reported interval extends below and above 1, so it is compatible with effects in either direction as well as no difference.

What is the role of the p-value?

The sponsor reports p = 0.591 for the primary superiority analysis. General explanation: a p-value describes how unusual data at least as incompatible with a specified null hypothesis would be if that null hypothesis and the test assumptions held. It is not the probability that the null hypothesis is true, and it does not measure the size or clinical importance of an effect. The p-value should be interpreted alongside the estimated rate ratio and its confidence interval, not in isolation.

A simple recalculation from the posted arm-level rates and confidence intervals yields a rate ratio of 1.134, a 95% confidence interval from 0.707 to 1.818, and an unadjusted p-value of 0.602. That calculation is a summary-statistic check, not a reproduction of the negative binomial model. The registry record does not give enough model detail to reconstruct the sponsor’s analysis from first principles. Small differences between the two sets of estimates are therefore best described as results from different analysis approaches, without assigning a specific cause that is not reported.

How does the secondary time-to-event analysis differ?

The secondary time-to-first-exacerbation result uses a Cox regression analysis and is expressed as a hazard ratio. General explanation: a hazard ratio compares the instantaneous event rates among participants who have not yet experienced the event, under the model’s assumptions. It is not the same quantity as a rate ratio for all exacerbations, since the time-to-first analysis counts only the first event for this purpose. A hazard ratio of 1 represents equal hazards. The registry reports 1.12, with a 95% confidence interval from 0.67 to 1.91 and p = 0.668.

Median time-to-event estimates describe the time by which half of the relevant event-time distribution has been reached, subject to the analysis and censoring. The registry reports medians of 233.0 days for benralizumab and 316.0 days for placebo. The reported confidence limits are incomplete on the upper side for both groups, with no upper confidence limit reported. These medians should not be treated as interchangeable with the primary annualized rates.

Finally, the Full Analysis Set is defined as all randomized participants who received at least one dose, regardless of adherence or continued participation. That definition identifies who contributes to the primary analysis, but it does not tell the reader how missing outcome observations were handled, whether follow-up time was censored in a particular way, or what sensitivity analyses were conducted. Those details are not reported in the registry record.

11. Confidence Intervals and Precision

The primary rate ratio is 1.14, with a 95% confidence interval from 0.71 to 1.82. The interval is wide enough to include values below 1 and above 1. In practical statistical terms, the posted data leave considerable uncertainty about the direction and size of the relative rate difference. The p-value of 0.591 is consistent with the interval’s failure to exclude the no-difference value, but neither statistic proves that the groups are equivalent.

The arm-specific annualized rates are 1.44 exacerbations per year for benralizumab, with a 95% confidence interval from 1.05 to 1.97, and 1.27 for placebo, with a 95% confidence interval from 0.89 to 1.8. Each interval describes uncertainty in an arm-level rate estimate. The comparison interval is the more direct measure of uncertainty for the relative treatment contrast; arm-level intervals alone do not answer whether the groups differ.

The time-to-first-exacerbation hazard ratio is 1.12, with a 95% confidence interval from 0.67 to 1.91. This interval is also compatible with either a lower or a higher hazard relative to the reference value of 1. The registry reports median estimates of 233.0 days and 316.0 days, with lower confidence limits of 118.0 days and 141.0 days, respectively; upper limits are not reported. That missing upper-limit information further restricts how fully the precision of the medians can be described.

Confidence intervals describe statistical uncertainty under their respective models and do not capture every limitation, such as uncertainty about missing-data handling or whether the planned analysis was followed. They also do not establish clinical importance. The registry record does not report a threshold for a clinically important difference in exacerbation rate.

12. Planning a Similar Trial: Sample Size

This is a planning illustration, not a re-evaluation of the original trial. It asks: if a new study wanted to detect a difference like the one observed, or a smaller one, how large would it need to be? It is deliberately not “observed power” of the finished trial, which is not a meaningful quantity.

The sample-size illustrations are planning calculations based on the observed effect, not the study’s original design assumptions. For the primary rate comparison, the figures are participants per arm. For the time-to-first-exacerbation analysis, the figures are total events across the comparison, not participants per arm. These are different units and should not be compared as though they represented the same quantity.

The planning illustrations assume a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. The effect to detect is set to the stated fraction of the observed effect. The registry’s own original sample-size justification and design assumptions are not reported in the registry record.

The 80% power column describes the number of participants per arm, or total events for the time-to-event calculation, that the planning calculation indicates would be needed to have an 80% chance of detecting the specified effect under those assumptions. The 90% power column describes the corresponding requirement for a 90% chance. These are conditional planning quantities, not predictions about the actual trial result.

Rows planning for 100% of the observed effect use the full observed effect as the target; rows for 75% and 50% use smaller target effects. Smaller effects are harder to distinguish from no effect, so the calculations require more participants or events. The posted primary illustrations are 1,374 participants per arm for 80% power and 1,839 for 90% power when planning for 100% of the observed effect; for 75% of the observed effect, they are 2,479 and 3,318; and for 50%, they are 5,661 and 7,578. The time-to-event illustrations are total-event counts under the same effect fractions. These calculations are not observed power.

13. How the Sample Size Is Derived

Power is the probability that a study of a given size rejects the null hypothesis when a specific true effect exists. It depends on four things: the effect to detect, the variability of the outcome, the significance level (here a two-sided α of 0.05, so z_1−α/2 = 1.960) and the desired power (z_1−β = 0.842 for 80% and 1.282 for 90%).

Formula

n is the number of participants in each arm, λ₀ and λ₁ are event rates per patient-year, and T is follow-up per participant in years. This assumes Poisson counts and equal follow-up.

Worked calculation for this trial

1. Control rate λ₀ = 1.2700; treatment rate λ₁ = 1.4400 events per patient-year; follow-up T = 0.54 years.
2. n = (1.96 + 0.842)² × (1/1.2700 + 1/1.4400) / (0.54 × [ln(1.134)]²) = 1,373.4, rounded up to 1,374 participants per arm for 80% power.

The smaller-effect rows in the table above repeat the same calculation with the effect multiplied by 0.75 and 0.5 (for ratios, applied to the logarithm of the ratio).

R code

alpha <- 0.05
z_a   <- qnorm(1 - alpha / 2)          # two-sided
lambda0 <- 1.27                      # control rate, events per patient-year
lambda1 <- 1.44                      # treatment rate
tt      <- 0.536604062859333                       # follow-up per participant, years
n_per_arm <- function(power, frac = 1) {
  l1 <- lambda0 * (lambda1 / lambda0)^frac   # smaller effect = fraction of the observed log rate ratio
  ceiling(round((z_a + qnorm(power))^2 * (1 / lambda0 + 1 / l1) / (tt * log(l1 / lambda0)^2), 6))
}
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: n per arm = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(n_per_arm(0.80, f), big.mark = ","), format(n_per_arm(0.90, f), big.mark = ",")))

# Simulation 1: Poisson counts. Simulation 2: over-dispersed counts (variance = 1.5 x mean), analysed with the matching variance.
set.seed(5006573)
n    <- n_per_arm(0.80)
reps <- 20000
m0 <- lambda0 * n * tt; m1 <- lambda1 * n * tt
x0 <- rpois(reps, m0); x1 <- rpois(reps, m1)
z  <- log(x1 / x0) / sqrt(1 / x0 + 1 / x1)
cat(sprintf("Simulated power, Poisson counts, n = %s per arm: %.3f\n", format(n, big.mark = ","), mean(abs(z) > z_a, na.rm = TRUE)))
phi <- 1.5
y0 <- rnbinom(reps, mu = m0, size = m0 / (phi - 1)); y1 <- rnbinom(reps, mu = m1, size = m1 / (phi - 1))
z2 <- log(y1 / y0) / sqrt(phi * (1 / y0 + 1 / y1))
cat(sprintf("Simulated power, over-dispersed counts (phi = 1.5), same n: %.3f\n", mean(abs(z2) > z_a, na.rm = TRUE)))

Output from running the code

100% of observed effect: n per arm = 1,374 (80% power), 1,839 (90% power)
 75% of observed effect: n per arm = 2,479 (80% power), 3,318 (90% power)
 50% of observed effect: n per arm = 5,661 (80% power), 7,578 (90% power)
Simulated power, Poisson counts, n = 1,374 per arm: 0.803
Simulated power, over-dispersed counts (phi = 1.5), same n: 0.630

The first simulation draws Poisson counts and should land close to the target power. The second allows extra variability (variance 1.5 times the mean, a purely illustrative value), which lowers the power at the same sample size, so rate trials usually need more participants than the Poisson formula suggests.

14. Analyses Reported by the Sponsor

The sponsor’s reported primary analysis uses a negative binomial model and gives a rate ratio of 1.14, a 95% confidence interval from 0.71 to 1.82, and p = 0.591. The simple recalculation from posted arm-level summary statistics gives a rate ratio of 1.134, a 95% confidence interval from 0.707 to 1.818, and an unadjusted p-value of 0.602.

The recalculation uses the displayed rates and confidence intervals and is not a refitting of the sponsor’s negative binomial model. It is useful as a check on the direction and approximate scale of the comparison, but it cannot reproduce model details that the registry does not report. The two approaches yield broadly similar estimates, while their exact values and p-values differ. The reason for each difference is not reported in the registry record.

For the primary inferential result, the sponsor’s own model-based analysis is the relevant reported analysis. The recalculation should be identified as a separate, unadjusted summary-statistic calculation rather than presented as an alternative sponsor result. Both estimates are centered above 1, and both confidence intervals include 1; neither provides a precise estimate that excludes no difference.

15. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary endpoint and a range of secondary outcomes, including time to first exacerbation, quality-of-life measures, and lung function. When an analysis includes multiple outcomes or repeated opportunities to test effects, interpreting each p-value as if it were the only test can overstate the strength of evidence. General explanation: multiplicity procedures can limit that problem by adjusting tests, defining a hierarchy, or distinguishing confirmatory from exploratory outcomes.

The multiplicity strategy, the ordering or hierarchy of secondary endpoints, and whether reported p-values were adjusted are not reported in the registry record. The primary p-value is reported as 0.591 and the time-to-first-exacerbation p-value as 0.668, but the record does not state how these tests fit into any broader testing strategy. The other listed secondary outcomes do not have numerical comparative results reported in the registry record. Claims based on a selective subset of outcomes would therefore be especially difficult to evaluate.

The registry defines the Full Analysis Set as all randomized participants who received at least one dose of investigational product, regardless of protocol adherence or continued participation. This clarifies the stated primary analysis population. It does not, by itself, specify how missing endpoint data were treated, how participants who discontinued were handled in the model, or whether sensitivity analyses assessed assumptions about missingness. Those methods are not reported in the registry record.

The reason for the terminated status is also not reported in the registry record. Without that information, it is not possible to determine whether termination affected recruitment, follow-up, endpoint ascertainment, or the planned analysis. The registry does not report interim analyses, stopping rules, or the original sample-size justification. These omissions limit assessment of how the posted analyses relate to the study’s original statistical plan; they are not evidence that any particular method was or was not used.

16. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: bronchiectasis (14.8%), incarcerated inguinal hernia (2.6%), intestinal obstruction (2.6%), covid-19 (2.6%), pneumonia pseudomonal (2.6%).

During the double-blind period, serious adverse events affected 10 of 54 participants in the benralizumab group and 3 of 45 in the placebo group. Other adverse events affected 33 of 54 and 18 of 45, respectively. The registry lists zero deaths in each double-blind group. These are descriptive counts of participants affected, not estimates of comparative risk adjusted for follow-up or other factors.

For the open-label extension, serious adverse events affected 5 of 38 participants in the benralizumab group and 4 of 40 participants who switched from placebo to benralizumab. Other adverse events affected 9 participants in each group, and the registry lists zero deaths in both extension groups. The extension is open-label and has no concurrent placebo group, so these figures do not retain the blinded randomized comparison.

Serious adverse event terms listed in the registry include Bronchiectasis at 14.8%, and Incarcerated inguinal hernia, Intestinal obstruction, COVID-19, Pneumonia pseudomonal, and Hypertension at the listed percentages. The registry record does not provide additional context for interpreting these term-level percentages. Adverse event counts alone do not establish causation, and differences in follow-up or participant selection should be considered when reading the double-blind and extension figures.

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

The primary result is an estimate of the relative annualized exacerbation rate during the double-blind period. The sponsor’s negative binomial analysis reports a rate ratio of 1.14, with a 95% confidence interval from 0.71 to 1.82 and p = 0.591. The interval includes the no-difference value and spans estimates on either side. The data therefore leave substantial uncertainty about the direction and magnitude of the relative rate difference.

This result does not demonstrate equivalence. Establishing equivalence would require a suitable design and a prespecified margin, neither of which is reported in the registry record. Nor does the point estimate alone establish that one group had a reliably higher underlying rate. A non-significant result is not proof that the treatments have identical effects, and it is not a measure of whether any effect would be clinically important.

The secondary time-to-first-exacerbation result is a separate analysis, with a hazard ratio of 1.12 and a 95% confidence interval from 0.67 to 1.91. It addresses time to the first event, rather than the rate of all exacerbations, and is also imprecise. Numerical results for the other listed secondary outcomes are not reported in the registry record, so they cannot establish a broader pattern of benefit or harm.

The registry also reports adverse-event counts for the double-blind period and the open-label extension. Those counts describe events recorded in the listed groups, but do not by themselves show that treatment caused an event or provide a complete comparative safety assessment. The extension’s groups both received benralizumab, and the extension is not a continued blinded comparison.

Finally, the record’s terminated status should be noted, but the reason is not reported. It cannot be used on its own to infer that the study was stopped for efficacy, safety, recruitment, or another reason. The results describe the posted analyses and their precision; they do not settle questions the registry record does not address.

18. Why This Trial Matters Statistically

This study illustrates why the endpoint and its analysis scale matter. The primary outcome is an annualized event rate, designed to account for differing exposure time and repeated exacerbations. Its interpretation differs from an analysis of whether any participant experienced an event or an analysis of time until the first event. The registry includes both the rate comparison and a time-to-first comparison, but they answer distinct questions.

The results also show why a point estimate should not be read without its confidence interval. The primary rate ratio is 1.14, but the 95% confidence interval from 0.71 to 1.82 includes values below and above the no-difference value. The estimate’s direction alone cannot resolve the uncertainty. The separate time-to-first analysis has the same broad interpretive issue: its interval includes the no-difference value and is wide.

Another statistical issue is the difference between a sponsor’s model-based analysis and a simple recalculation from arm-level summaries. The negative binomial model is the reported primary approach; a recalculation can serve as a check but cannot reconstruct analysis details not reported in the registry. Keeping those approaches distinct avoids treating a summary-statistic calculation as though it were the trial’s full analysis.

Finally, many secondary outcomes can enrich a study’s scientific questions, but they also require transparent reporting and careful attention to multiplicity. In this record, the numerical comparative results for most listed secondary measures are not reported, and the multiplicity strategy is not reported. Those gaps matter when assessing how much weight to place on secondary evidence. The study is therefore a useful example of interpreting effect estimates, uncertainty, analysis populations, and reporting limits together rather than reducing the assessment to a single p-value.

19. 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.
• Rate comparisons use a Poisson approximation unless the sponsor posted confidence limits; real event counts are often over-dispersed.

The registry record identifies the study as terminated but does not report the reason. It is therefore not possible to determine from the record whether termination affected enrollment, follow-up, the number of observed exacerbations, or the intended analysis. The record lists enrollment of 100, while the primary analysis groups include 54 participants receiving benralizumab and 45 receiving placebo. The registry does not explain the relationship between the enrollment figure and the analysis-group counts.

The double-blind treatment period varied from at least 28 weeks up to 52 weeks according to randomization timing and the effective date of a revised protocol. Annualization addresses exposure time in the rate endpoint, but the registry does not report the distribution of follow-up or the detailed handling of incomplete observation. Missing-data procedures, sensitivity analyses, and the extent of missing outcome information are not reported in the registry record.

The registry does not report the study’s original sample-size justification, detailed model covariates, interim analyses, or multiplicity strategy. It also does not provide numerical comparative results for most listed secondary outcomes. These reporting gaps constrain evaluation of the design and of consistency across outcomes. The planning illustrations based on the observed effect are not a substitute for the study’s original design rationale.

The open-label extension has no placebo group because participants in both listed groups received benralizumab. Extension safety counts therefore should not be interpreted as a randomized comparison. The registry record also does not provide enough detail to explain the term-level serious adverse event percentages or to establish causal relationships between treatment and events.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of Benralizumab in Patients With Non-cystic Fibrosis Bronchiectasis — NCT05006573.
• Registry record last updated 2025-07-20; status last verified 2025-07.
• Results first posted 2025-07-20.
• 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.

23. Record Summary

The registry describes a randomized, triple-masked, parallel-group phase III study of benralizumab 30 mg versus matching placebo, on top of standard-of-care therapy, in adults with non-cystic fibrosis bronchiectasis and eosinophilic inflammation. The double-blind period lasted at least 28 weeks and up to 52 weeks, with an open-label extension in which all participants received benralizumab.

The primary endpoint was annualized bronchiectasis exacerbation rate. The sponsor’s negative binomial analysis reported a rate ratio of 1.14, with a 95% confidence interval from 0.71 to 1.82 and p = 0.591. This estimate is imprecise and its interval includes the no-difference value. The record lists the study as terminated; the reason, original sample-size justification, missing-data methods, and multiplicity strategy are not reported in the registry record.