Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma (NCT02443298), a randomized phase 2 study. The primary outcome is Time to First Asthma Worsening During the Planned 24 Week Treatment Period.

2. Clinical Question

The registry describes the study as randomized, double-blind, and parallel-group. Its stated objectives were to evaluate efficacy and safety and, following a meaningful clinical response, to identify biomarkers that might help target patients likely to respond. The posted primary result addresses the time-to-first-worsening endpoint; it does not establish whether any particular patient subgroup benefits, or whether a biomarker can identify such a subgroup.

3. Trial Design

This was a phase IIa, randomized, double-blind, placebo-controlled, parallel-group study in patients with severe persistent asthma. The registry lists 214 participants as enrolled and marks the study completed. The trial evaluated risankizumab as add-on therapy over a planned 24-week treatment period. The registry record gives a start date of 2015-06-23 and a primary completion date of 2017-10-13.

Patients assigned to risankizumab received subcutaneous injections once every 4 weeks at weeks 0, 4, 8, 12, 16, and 20. The placebo group received matching injections on the same schedule. The primary analysis population is described as the Full Analysis Set, comprising all randomized patients who received at least one dose of treatment. The posted result gives 105 patients in the risankizumab group and 109 in the placebo group for this endpoint.

The primary endpoint was time to first asthma worsening during the planned 24 weeks. Secondary outcomes included an alternative definition of asthma worsening, annualized worsening and severe-exacerbation rates, time to first severe exacerbation, lung-function measures, and an asthma control questionnaire score. The registry lists those outcomes but does not provide posted numerical results for every outcome in the registry record considered in this analysis.

The registry record does not report the original sample-size justification, the trial's planned power or significance threshold, interim analyses, detailed allocation procedures, or the full statistical analysis plan. Those details should not be inferred from the posted endpoint results or from planning illustrations based on the observed effects.

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 were screened for eligibility to participate in the trial. Patients attended a specialist sites which ensured that they (the patients) met all strictly implemented inclusion/exclusion criteria. Patients were not to be randomized to trial treatment if any one of the specific entry criteria was violated.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Full Analysis Set (FAS): All randomized patients who received at least one dose of treatment.

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: Randomized Set (RS): This patient set included all randomized patients, whether treated or not.

6. Primary Endpoint

The registry lists the primary outcome as Time to First Asthma Worsening During the Planned 24 Week Treatment Period, measured over 24 weeks.

The primary endpoint measures the time from the start of the treatment period until a patient's first qualifying asthma worsening, within the planned 24 weeks. It is a time-to-event outcome: the event is the first worsening that meets the trial definition, and the time records when it occurs. Patients without a recorded event during follow-up contribute information up to the point their follow-up ends, as handled by the analysis. The registry record does not report the detailed censoring rules.

Worsening could be triggered by any one of four criteria: a decrease from baseline of at least 30% in morning peak expiratory flow on at least 2 consecutive days; an increase from baseline of at least 50% and at least 4 puffs in daily rescue medication use for at least 2 consecutive days; an increase from baseline of at least 0.75 units in ACQ5; or a severe asthma exacerbation. The exacerbation definition included initiation of systemic corticosteroids for 3 or more consecutive days. For patients on maintenance systemic corticosteroids, at least doubling the maintenance dose to a total daily dose of at least 20 mg for 3 or more consecutive days also counted.

As a general statistical explanation, time-to-event endpoints use both whether an event occurs and how long it takes to occur, while allowing follow-up time to differ across participants. This can be useful when the timing of worsening matters, rather than only whether a patient has worsened by a fixed visit. The primary endpoint is a composite: different clinical or treatment-use criteria can qualify as an event. The registry record does not report how often each component individually accounted for primary events.

7. Results Posted in the Registry

• Risankizumab vs Placebo: hazard ratio 1.46 (95% CI 1.18–1.81), reported p = 0.025 (as reported in the registry).

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 Asthma Worsening During the Planned 24 Week Treatment Period According to Alternative Definition

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Cox proportional hazards model); it was not recalculated.
• Result:
  • Risankizumab vs Placebo: hazard ratio 1.47 (95% CI 1.20–1.79), reported p = 0.013 (as reported in the registry).
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the hazard of the event is statistically higher for Risankizumab vs Placebo than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Annualized Rate of Asthma Worsening During the Planned 24 Week Treatment Period

• Endpoint type: Event rate: events per unit of follow-up, compared as a rate ratio.
• Test: Poisson rate ratio, based on the estimated number of events and follow-up time.
• Result:
  • Risankizumab: 4.84 versus 3.24 (Events per patient year) on control; rate ratio 1.49 (95% CI 1.22–1.82, approximate, Poisson model); p ≈ <0.001.
• Interpretation:
  • The 95% confidence interval excludes no difference (a ratio of 1), so the event rate is statistically higher for Risankizumab than for the control. This is an unadjusted, secondary comparison, so it is suggestive rather than confirmatory.

Time to First Severe Asthma Exacerbation During the Planned 24 Week Treatment Period

• Endpoint type: Time to event: compared as a hazard ratio.
• Test: Hazard ratio as reported by the sponsor (Cox proportional hazards model); it was not recalculated.
• Result:
  • Risankizumab vs Placebo: hazard ratio 1.18 (95% CI 0.88–1.57), reported p = 0.462 (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 Risankizumab vs Placebo and the control. The interval gives the range of effects that remain compatible with the data.

The secondary outcomes cover several related aspects of asthma: alternative worsening criteria, annualized rates of worsening and severe exacerbation, time to first severe exacerbation, lung function, and asthma control. They provide different views of disease worsening and its measurement, rather than repeated versions of a single endpoint. The record posts numerical results for some secondary analyses, but not all secondary endpoints have numerical results in the registry record.

The available secondary results do not all provide the same kind of evidence. Time-to-event outcomes use hazard ratios, while event-rate outcomes use rates and rate comparisons; those quantities answer different questions. They should not be combined into a single overall estimate. The primary endpoint remains the central prespecified comparison described in the registry summary, and secondary outcomes are contextual evidence about other measures during the same treatment period.

Unadjusted secondary results carry less weight when several outcomes are examined because the chance of at least one apparently notable result can increase across multiple tests. A multiplicity procedure can address that issue, but the registry record does not report whether secondary analyses were adjusted, how they were ordered, or which were confirmatory. The reported secondary p-values should therefore not be treated as equivalent to a single primary test with a prespecified testing plan.

The broad pattern across the posted outcomes should be interpreted with this distinction in mind: they can add context to the primary time-to-first-worsening result, but they cannot establish that every outcome moved in the same direction or that any secondary finding is definitive. The registry record does not report complete numerical results for every listed secondary endpoint, so a comprehensive cross-endpoint comparison is not possible from these registry entries.

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

• Time to First Asthma Worsening During the Planned 24 Week Treatment Period According to Alternative Definition
• Annualized Rate of Asthma Worsening During the Planned 24 Week Treatment Period
• Time to First Severe Asthma Exacerbation During the Planned 24 Week Treatment Period
• Annualized Rate of Severe Asthma Exacerbation During the Planned 24-week Treatment Period
• Trough Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24
• Post-bronchodilator Forced Expiratory Volume in 1 Second (FEV1) In-clinic Change From Baseline at Week 24
• Weekly Asthma Control Questionaire Score at Week 24

9. Statistical Interpretation

10. Statistical Methods Explained

Time to first worsening was analyzed with a Cox proportional hazards model, according to the sponsor's reported analysis. A Cox model compares the rate at which the event occurs over follow-up between groups, using the ordering and timing of observed events. It can incorporate participants whose event was not observed before their follow-up ended, although the registry record does not give the detailed censoring rules used for this analysis.

What does the hazard ratio describe?

The reported hazard ratio is 1.46 for risankizumab versus placebo. A hazard is an instantaneous event rate among people who have not yet experienced the event. A hazard ratio compares those rates between groups, conditional on the model and its assumptions. It is not a ratio of the medians, a difference in days, or the probability that a particular participant will worsen. In the reported contrast direction, a value above 1 corresponds to a higher event hazard for risankizumab than for placebo. The observed medians point in the same direction.

One central Cox-model assumption is proportional hazards: the relative hazard between groups is treated as constant over follow-up. The registry record identifies the model but does not report a diagnostic assessment of that assumption, whether it was met, or whether time-varying effects were considered. A hazard ratio can be difficult to summarize if the relative hazards change substantially over time, so the estimate should be interpreted as a model-based summary rather than a complete description of every point in the follow-up period.

Why report medians as well?

The median time to first worsening gives a time-scale summary that is easier to relate to the duration of follow-up than a hazard ratio. It is the estimated time by which half of the group has experienced the event. The posted medians were 40.0 days for risankizumab and 85.5 days for placebo. Their accompanying 80% confidence intervals indicate uncertainty in each median estimate. Comparing two medians alone does not provide the same information as the Cox model, and the registry does not report a separate test of the median difference.

Time-to-event methods are generally useful when participants can have different lengths of follow-up or when some do not experience the event before observation ends. As a general statistical explanation, censoring means that the exact event time is unknown for a participant whose observation ends before a qualifying event; their observed follow-up can still inform the analysis. The record does not report the number or reasons for censored observations, missing endpoint data, or the specific censoring conventions. These omissions limit independent assessment of how incomplete follow-up affected the result.

How should the p-value be read?

The sponsor reported p = 0.025 for the primary comparison. A p-value describes how unusual data at least as incompatible with the model's null hypothesis would be if that null hypothesis and the analysis assumptions were true. It is not the probability that the null hypothesis is true, nor the probability that the result arose by chance. The registry record does not report a trial-wide multiplicity plan or the original testing hierarchy, so the p-value should be read as the reported result for this endpoint rather than as evidence that all outcomes were tested without concern for multiple comparisons.

The significance level and power assumptions for the trial's original design are not reported in the registry record. A separate planning illustration based on the observed effect uses a two-sided significance level of 0.05, equal allocation, and a normal approximation. That illustration is not evidence about the design choices used by the investigators. For time-to-event calculations, the planning quantity is the total number of events, not the number of participants per arm.

What does the endpoint definition imply?

The primary outcome is a composite endpoint: any one of several specified changes can count as worsening. Composite endpoints can capture multiple clinically relevant forms of deterioration, but the overall result depends on the events making up the composite. Here, qualifying components include changes in peak expiratory flow, rescue medication use, ACQ5, and severe exacerbation. The registry record does not report the number or proportion of events attributable to each component, so the overall hazard ratio cannot be assigned to any single component.

The primary analysis population excludes randomized patients who did not receive at least one dose, according to the stated Full Analysis Set definition. The registry record does not report the numbers excluded from that population, how missing data were handled, or sensitivity analyses for alternative assumptions. The posted Cox result is the sponsor's analysis; it is the appropriate source for the reported treatment comparison, while planning calculations based on summary results remain illustrative rather than a substitute for the trial analysis.

11. Confidence Intervals and Precision

The primary median estimates are 40.0 days for risankizumab and 85.5 days for placebo. Their 80% confidence intervals are 30.0 to 52.0 days and 63.0 to 131.0 days, respectively. The intervals communicate uncertainty about the median estimates; they are not ranges containing 80% of individual participants' event times. The registry reports 80% intervals, so they should not be described as 95% confidence intervals.

For the sponsor-reported hazard ratio of 1.46, the 80% confidence interval is 1.18 to 1.81. The interval lies above 1, indicating that the reported model-based range is on the side of a higher event hazard for risankizumab relative to placebo. Its width reflects uncertainty about the magnitude of the relative hazard. The interval does not show the range of effects that are equally plausible, and it does not account for limitations such as unreported model diagnostics or multiplicity handling.

As a general statistical explanation, a confidence interval is a procedure that, under its assumptions and repeated use, captures the target parameter at the stated rate. It is not a probability statement about whether the specific fixed parameter lies inside this particular interval. An interval also does not decide whether an effect is clinically important: that requires a clinical interpretation or threshold, which the registry record does not report.

The median confidence intervals overlap, but overlap alone is not a formal test of the difference between medians. The reported Cox model provides the trial's inferential comparison. The registry record does not report a 95% interval for the primary hazard ratio, so one should not infer it from the posted 80% interval. Precision is therefore best described using the reported estimates and their stated 80% intervals, without extending them beyond what the record reports.

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 planning figures are illustrations based on the observed effect, not the trial's own design calculations. For time-to-event endpoints, the figures are total events needed. For other outcomes, the figures are participants per arm. The assumptions are a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation; the effect to detect is the stated fraction of the observed effect. The trial's original design assumptions are not reported in the registry record.

The 80% power column describes a planning scenario with an 80% chance of detecting the specified effect under the stated assumptions, if the effect and assumptions are correct. The 90% power column describes the corresponding scenario with a 90% chance. These are design probabilities, not probabilities that the trial's result is correct. This is not observed power.

Rows that plan for 75% or 50% of the observed effect assume a smaller effect than the full observed effect. Smaller effects are harder to distinguish from random variation, so they require more information: more total events for time-to-event outcomes or more participants per arm for other outcomes. The figures are therefore sensitivity illustrations showing how planning needs change as the assumed target effect becomes more modest.

For the primary time-to-event comparison, the displayed planning quantity is total events. It should not be mistaken for a participant count or for the number enrolled in this trial. The calculations are not a reanalysis of the study's original design, and the registry record does not report that these assumptions were used when the trial was planned.

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

d is the total number of events needed (Schoenfeld's formula) with 1:1 allocation and proportional hazards.

Worked calculation for this trial

1. Hazard ratio HR = 1.460, so ln(HR) = 0.3784.
2. d = 4 × (1.96 + 0.842)² / [ln(1.460)]² = 219.2, rounded up to 220 events in total 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
hr <- 1.46                              # observed hazard ratio
events_needed <- function(power, frac = 1) ceiling(round(4 * (z_a + qnorm(power))^2 / log(hr^frac)^2, 6))   # Schoenfeld, 1:1 allocation
for (f in c(1, 0.75, 0.5))
  cat(sprintf("%3.0f%% of observed effect: events = %s (80%% power), %s (90%% power)\n", 100 * f,
              format(events_needed(0.80, f), big.mark = ","), format(events_needed(0.90, f), big.mark = ",")))

# Simulation: given d total events under proportional hazards, events in the treatment arm are Binomial(d, hr / (1 + hr)).
# The score (log-rank type) statistic is (D1 - d / 2) / sqrt(d / 4).
set.seed(2443298)
d    <- events_needed(0.80)
reps <- 20000
D1 <- rbinom(reps, d, hr / (1 + hr))
z  <- (D1 - d / 2) / sqrt(d / 4)
cat(sprintf("Simulated power with %s events: %.3f (%d replicates)\n", format(d, big.mark = ","), mean(abs(z) > z_a), reps))

Output from running the code

100% of observed effect: events = 220 (80% power), 294 (90% power)
 75% of observed effect: events = 390 (80% power), 522 (90% power)
 50% of observed effect: events = 877 (80% power), 1,174 (90% power)
Simulated power with 220 events: 0.795 (20000 replicates)

The simulation uses the fact that, with d events in total and proportional hazards, the number of events in the treatment arm is binomial. It is an approximation that conditions on the total number of events, and it should land close to the target power.

14. Analyses Reported by the Sponsor

The sponsor's reported primary analysis is a Cox proportional hazards model comparing risankizumab with placebo. It reports a hazard ratio of 1.46, an 80% confidence interval from 1.18 to 1.81, and p = 0.025. The medians and intervals are also posted for each group. These results describe the sponsor's analysis of the trial endpoint.

No alternative recalculation is used to replace this primary result. For a time-to-event outcome, a simple reanalysis of summary medians would not reproduce a Cox model, which uses the event timing and follow-up information. The registry record does not provide the participant-level data needed to independently refit that model. The sponsor's reported analysis therefore takes precedence for the primary inferential comparison.

The reported hazard-ratio direction, together with the group medians, indicates that first worsening occurred sooner in the risankizumab group in the posted analysis. This interpretation remains subject to the model assumptions and the information not reported in the registry record, including model diagnostics and detailed handling of censoring and missing data. The reported p-value and confidence interval should be read as outputs of the sponsor's analysis, not as independent confirmation of its assumptions.

15. Multiplicity, Missing Data and Analysis Populations

The registry record lists a primary endpoint and multiple secondary outcomes, but does not report a multiplicity adjustment, a hierarchy of hypothesis tests, or which secondary comparisons were intended to be confirmatory. When multiple outcomes are tested, unadjusted p-values do not by themselves control the overall chance of a false-positive finding across the collection of tests. This is why the primary result and secondary results should not automatically be given the same inferential weight.

The record defines the primary analysis population as the Full Analysis Set: all randomized patients who received at least one dose of treatment. It does not report the number of randomized patients who did not receive a dose, the numbers included in each secondary analysis, or whether analysis populations differed by endpoint. The term Full Analysis Set should not be assumed to mean that every randomized patient was analyzed if the stated definition excludes those who received no treatment.

Detailed missing-data methods are not reported in the registry record. The registry entries do not describe how missing endpoint measurements, withdrawals, loss to follow-up, or incomplete treatment-period observations were handled. For a time-to-event analysis, censoring conventions and the amount of censored follow-up can affect interpretation, but the relevant details are not reported. The record also does not report sensitivity analyses testing alternative assumptions about missing or censored data.

The full statistical analysis plan, interim-analysis procedures, and the original design assumptions are not reported in the registry record. These omissions do not negate the posted estimates, but they limit assessment of whether all analysis choices were prespecified and how the reported p-values relate to the full set of planned comparisons. Accordingly, the primary analysis is best read as the sponsor-reported result, while secondary and unadjusted findings should be treated as supportive or exploratory unless the registry record documents otherwise.

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: asthma (5.7%), pneumonia (1.8%), sudden hearing loss (1.0%), epstein-barr virus infection (1.0%), respiratory syncytial virus infection (1.0%).

The registry reports serious adverse events in 14 of 105 patients in the risankizumab group and 21 of 109 patients in the placebo group. It reports zero deaths in each group. Other adverse events were reported for 84 patients in the risankizumab group and 80 in the placebo group. These are separate posted counts; the record does not provide a causal assessment for each event in the registry record.

The listed serious-event terms include asthma at 5.7%, pneumonia at 1.8%, sudden hearing loss at 1.0%, Epstein-Barr virus infection at 1.0%, respiratory syncytial virus infection at 1.0%, and intervertebral disc protrusion at 1.0%. These entries identify reported event terms, not proof that treatment caused them. The registry record does not provide the full event-level detail, timing, severity grading, or investigator attribution needed to assess individual cases.

As a general statistical point, adverse-event counts describe what was observed in the study groups; they do not alone establish whether a treatment caused an event or whether a difference is meaningful. These results should be interpreted alongside the trial's duration, population, and the limitations of the registry record. They do not provide a basis for medical advice.

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

The primary result estimates the timing of first asthma worsening under the trial's composite definition during a planned 24-week period. The posted medians were shorter in the risankizumab group than in the placebo group, and the sponsor-reported hazard ratio was above 1 for the stated risankizumab-versus-placebo contrast. The 80% confidence interval for that hazard ratio was 1.18 to 1.81, and the reported p-value was 0.025. These statistics describe the observed trial comparison and its model-based uncertainty.

The result does not establish why worsening occurred, which component of the composite drove the contrast, or whether the observed difference is clinically important. The registry record does not report a clinical-importance threshold or the component-specific event breakdown. The hazard ratio is not an individual probability, and the group medians are not predictions for any particular patient.

The result also does not establish effects beyond the studied population or treatment period. The registry record concerns patients with severe persistent asthma, add-on treatment, and a planned 24-week evaluation. It does not, in the registry record reported, establish long-term outcomes, subgroup-specific effects, or whether a biomarker can identify likely responders. The biomarker objective is described as conditional on a meaningful clinical response; no biomarker result is included in the registry record.

Safety counts are descriptive and do not by themselves establish causation. Secondary outcomes can provide context, but the registry record does not report a multiplicity plan that would make all secondary findings equally confirmatory. Missing details about censoring, missing data, and model diagnostics also constrain how fully the primary estimate can be independently assessed.

In short, the posted result is evidence about a randomized comparison in this trial, not a treatment recommendation or a definitive statement about all patients with asthma. It should be read with its endpoint definition, reported uncertainty, statistical assumptions, and unreported analysis details in mind.

18. Why This Trial Matters Statistically

This trial illustrates why a time-to-event result needs more than a single headline number. The median times give an interpretable description of when first worsening occurred, while the Cox hazard ratio summarizes the relative event hazard across follow-up. These statistics are related but not interchangeable: one is a time summary, and the other is a model-based relative comparison.

It also shows the importance of reading the direction of a contrast carefully. The reported comparison is risankizumab versus placebo, and the hazard ratio is above 1; the observed median is shorter for risankizumab. Both pieces of information point to earlier first worsening in that group under the endpoint definition. Interpreting the number without checking the group order could reverse its meaning.

The primary outcome is composite, bringing together physiological change, rescue medication use, a questionnaire score, and severe exacerbation. This can capture multiple ways that asthma may worsen, but it also makes component-specific results important for understanding what contributed to the overall endpoint. Those component results are not reported in the registry record.

Finally, precision and analysis context matter. The reported intervals are 80% confidence intervals, and the record does not report multiplicity handling, model diagnostics, or detailed missing-data procedures. Secondary findings and planning illustrations answer different questions from the primary sponsor analysis. Distinguishing observed trial estimates from planning scenarios helps prevent a sample-size illustration from being mistaken for evidence about the trial's achieved power or original design.

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.

The registry record does not report the original sample-size justification, planned power, or the significance threshold used in the trial's own design. The planning illustrations based on observed effects cannot fill that gap. It also does not report interim-analysis procedures or the full statistical analysis plan.

For the primary Cox analysis, the record does not report diagnostics for the proportional-hazards assumption, detailed censoring rules, or the amount and reasons for censored follow-up. The record does not describe missing-data handling or sensitivity analyses. These details would help assess how incomplete follow-up and modeling choices affect the estimate.

The primary endpoint combines several types of worsening, but component-specific event counts are not reported. As a result, the overall time-to-first-worsening result cannot be attributed to one particular component. The record also does not report a clinical threshold for interpreting the size of the difference in median time.

The record lists several secondary outcomes but does not provide numerical results for all of them in the registry record. It does not report multiplicity adjustment or a confirmatory hierarchy for secondary analyses. The available secondary findings therefore have limited ability to establish a coherent effect across outcomes.

Safety information is also limited in detail: the posted counts and selected serious-event terms do not provide complete event narratives, timing, severity grading, or causal attribution. These limitations concern what can be concluded from the registry record; they do not, on their own, establish that an analysis or event report is incorrect.

20. Related Tutorials

21. Related Statistical Calculators

22. Sources

• ClinicalTrials.gov: Efficacy and Safety of BI 655066/ABBV-066 (Risankizumab) in Patients With Severe Persistent Asthma — NCT02443298.
• Registry record last updated 2019-04-10; status last verified 2019-03.
• Results first posted 2019-04-10.
• 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 completed, randomized, double-blind, placebo-controlled, parallel-group phase IIa study of risankizumab as add-on therapy for severe persistent asthma. Treatment was planned over 24 weeks, with subcutaneous risankizumab or matching placebo administered once every 4 weeks. Enrollment was 214.

The primary outcome was time to first asthma worsening. The sponsor-reported Cox model gave a hazard ratio of 1.46 for risankizumab versus placebo, with an 80% confidence interval from 1.18 to 1.81 and p = 0.025. Median time to first worsening was 40.0 days for risankizumab and 85.5 days for placebo.

The registry also lists secondary efficacy and safety outcomes. Important analysis details, including the original design assumptions, multiplicity plan, missing-data methods, and model diagnostics, are not reported in the registry record.