Study to Evaluate the Safety and Efficacy of CAT-354: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study to Evaluate the Safety and Efficacy of CAT-354 (NCT00873860), a randomized phase 2 study. The primary outcome is Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92.

2. Clinical Question

The study focused on asthma control rather than a single physiological measure. The ACQ captures participant-reported night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item contributes to an overall score, with higher scores indicating poorer control. Comparing change from baseline is intended to describe how the score shifted over the treatment period, while accounting for each participant’s starting score in the endpoint definition.

The registry record lists 357 participants enrolled and describes a randomized, placebo-controlled, parallel-arm study. It lists secondary measures including time to first observed asthma control, lung function, peak expiratory flow, rescue medication use, quality of life, and patient global impression of change. These outcomes broaden the clinical questions, but they do not replace the primary ACQ comparison. Since endpoint estimates and uncertainty measures are not reported in the registry record, the relative outcomes of CAT-354 and placebo cannot be determined from the posted results.

3. Trial Design

This was a phase 2a randomized, placebo-controlled, parallel-arm trial sponsored by MedImmune LLC. The registry record lists asthma as the condition and describes the target population as adults with uncontrolled, moderate-to-severe, persistent asthma. Enrollment was 357. The study status is completed; the recorded start was 2009-06 and primary completion was 2010-08.

Participants were assigned to placebo or one of three CAT-354 regimens: 150 mg, 300 mg, or 600 mg. All regimens were described as subcutaneous injections administered on Day 1, 15, 29, 43, 57, 71, and 85. The trial used a parallel-arm structure, so the treatment groups were followed as separate groups rather than participants crossing from one treatment to another. The record identifies the allocation as randomized. Its masking field says triple, while the study title describes the trial as double-blind; the record does not explain this difference.

The primary endpoint was change from baseline in mean ACQ score at Day 92, with baseline recorded on Day 1 before dosing. The endpoint description states that results were reported for the overall ACQ score. The defined evaluable population included participants who received at least 4 doses, as well as participants who received at least 1 dose but discontinued before 4 doses for safety reasons. The precise analysis procedures used for the primary comparison are not reported in the registry record.

The listed secondary outcomes cover asthma control, lung function, home-recorded peak expiratory flow, rescue beta-2 agonist use, quality of life, and patient global impression of change. The registry lists 16 outcome measures and 29 analyses. These counts indicate a broad collection of planned or recorded outcome analyses, but do not establish which analyses were prespecified, how they were ordered, or how their results were interpreted. Those details are 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable population included all participants who received at least 4 doses of investigational product or received at least 1 dose but discontinued prior to receiving 4 doses due to safety reasons. Here, 'n' signifies those participants who were evaluable for this measure at specified time points for each arm, respectively.

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 who were randomized.

6. Primary Endpoint

The registry lists the primary outcome as Change From Baseline in the Mean Asthma Control Questionnaire (ACQ) Score at Day 92, measured over Day 1 and 92.

The primary endpoint was change from baseline in mean Asthma Control Questionnaire score at Day 92. Baseline was defined using the Day 1 assessment before dosing. The ACQ is a participant-reported measure of asthma control covering night-time waking, symptoms on waking, activity limitation, shortness of breath, wheeze, and rescue short-acting beta agonist use. Each item is rated on a 7-point Likert scale from 0, no impairment, to 6, maximum impairment. The overall score is the mean of the six item scores and ranges from 0, well controlled, to 6, extremely poor controlled.

Using a multi-item questionnaire can capture several aspects of a participant’s experience rather than relying on a single symptom or physiological measurement. A change-from-baseline endpoint describes the direction and size of the shift in the measure over follow-up, and the mean summarizes the group’s scores. The clinical meaning of a group mean still depends on the actual estimate, its uncertainty, and the context in which the questionnaire was used.

The registry record does not report the primary endpoint’s group estimates, standard deviations, confidence intervals, or a test of the treatment comparison. It therefore does not show the magnitude or precision of change in ACQ score for any trial arm. The endpoint definition alone cannot establish whether the groups differed or how large any difference may have been.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Statistical methods help turn trial observations into estimates that can be interpreted with appropriate uncertainty. The registry record specifies the design and primary endpoint, but many details needed to reproduce or fully assess the analysis are not reported in the registry record.

What does a change-from-baseline endpoint represent?

For each participant, a change-from-baseline measure relates a follow-up value to that participant’s starting value. The trial’s stated primary assessment was at Day 92, with baseline measured on Day 1 before dosing. A group mean then summarizes the participant-level changes in that group. This approach focuses on movement over time rather than the endpoint score alone. It still requires the actual group summaries and an analysis that accounts for the study design to estimate a treatment comparison.

The registry record describes the primary measure as a mean and identifies standard deviation as its dispersion measure. A standard deviation describes variation among observations within a group; it is not the same as the uncertainty in a group mean or a treatment contrast. The record does not provide the primary endpoint values, group standard deviations, standard errors, confidence intervals, or p-values. Accordingly, the degree of statistical uncertainty around the primary comparison cannot be assessed from the posted results.

How should a treatment contrast be understood?

A treatment contrast compares outcomes between assigned groups. In a randomized trial, the planned comparison can use the assigned treatment groups to assess whether observed outcomes differ, subject to the analysis population and handling of missing data. For a continuous outcome such as ACQ score, a contrast would ordinarily be expressed in the outcome’s units, with an uncertainty interval describing the range of values compatible with the analysis. These are general statistical concepts; the exact model, contrast, and interval method used in this trial are not reported in the registry record.

A confidence interval is a way to communicate the precision of an estimate, not a guarantee that the true effect lies within a particular interval. A narrow interval generally indicates greater precision than a wide interval, assuming the analysis and model are appropriate. No confidence interval for the primary treatment comparison is reported in the registry record, so neither its precision nor its compatibility with a range of effects can be evaluated.

What does the sample-size planning illustration mean?

The record describes a planning illustration based on the observed effect, rather than the trial’s own design justification. It specifies a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The illustration uses a stated fraction of the observed effect as the effect to detect. For time-to-event outcomes, the record says the planning quantity is total events; for other outcomes, it is participants per arm.

Such a calculation is a planning aid: it asks what sample size would be associated with a specified set of assumptions. It is not observed power, and it does not show the probability that the completed trial detected an effect. The underlying observed effect and resulting planning values are not reported in the registry record. The assumptions also do not establish that the same allocation or model was used for the actual primary analysis.

Over-dispersion is a general concern when observed variability is greater than a model assumes. If a statistical model understates variability, uncertainty estimates can be too small and tests can appear more decisive than warranted. The primary endpoint is described as continuous, but the registry record does not report an over-dispersion assessment or the model used. It would therefore be inappropriate to claim that over-dispersion was either present or addressed in this analysis.

How should adverse-event counts be read statistically?

Counts of affected participants are descriptive. The number at risk gives the group denominator recorded for the measure, while the number affected records participants with an event. These summaries do not reveal the timing, duration, severity, recurrence, or relationship of events to treatment. Nor do the counts alone quantify uncertainty around a between-group difference. An inferential safety comparison would require a defined outcome and analysis; such a comparison is not reported in the registry record.

Rare or infrequent events can be particularly difficult to compare because counts may be small and estimates uncertain. A zero count in a group means that no affected participants are listed for that group in the posted count; it does not prove that the underlying risk is zero. This is a general statistical point, not a claim about the cause or expected frequency of any event in this trial.

The registry lists 16 outcome measures and 29 analyses. Multiple outcomes and analyses raise questions about how results were selected and how the chance of false-positive findings was controlled. The record does not report a multiplicity procedure, a hierarchy of outcomes, or which analysis was designated as primary in the analysis plan beyond identifying the primary endpoint. The details needed to determine how multiple testing affected interpretation are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 16 outcome measures and 29 analyses, including the primary ACQ endpoint and secondary assessments of asthma control, lung function, peak expiratory flow, rescue medication use, quality of life, and patient global impression of change. When many outcomes or analyses are considered, the chance of at least one apparently notable result can increase. A prespecified hierarchy or multiplicity adjustment can help define how such results should be interpreted. The registry record does not report a multiplicity procedure, a testing hierarchy, or the allocation of statistical error across outcomes.

The record identifies the ACQ primary endpoint and its Day 92 assessment, but the precise statistical model and contrast for the primary analysis are not reported in the registry record. It does not state how repeated observations, if included in an analysis, were handled. No interim analyses or stopping rules are reported in the registry record, and no sample-size justification for the trial is reported in the registry record.

Missing data are a central concern for a change-from-baseline endpoint because not every enrolled participant necessarily contributes a value at each assessment. The primary population definition includes participants who received at least 4 doses, plus those who received at least 1 dose but stopped before 4 doses for safety reasons. This is the population definition recorded for the measure; it does not specify how missing Day 92 scores were handled. Methods such as imputation, complete-case analysis, or sensitivity analysis are not reported in the registry record, and the number of participants with endpoint data in each group is not reported in the registry record.

The record also does not describe whether the principal analysis followed randomized assignment regardless of treatment received, or whether any other analysis population was used. The distinction can affect interpretation, so the stated evaluable population should not be silently treated as equivalent to every possible analysis set. Without group-specific participant flow and missing-data methods, the risk of bias related to incomplete outcome data cannot be assessed from the registry record.

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 serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: asthma (4.3%), cardio-respiratory arrest (2.1%), sinusitis (2.1%), contusion (2.1%), overdose (2.1%).

The registry reports serious adverse events for each group using the number of participants at risk and the number affected. The entries are 3 affected among 47 at risk for placebo, 2 among 47 for CAT-354 150 mg, 0 among 51 for CAT-354 300 mg, and 1 among 48 for CAT-354 600 mg. These figures describe the counts recorded for the serious adverse event category; they should not be read as estimates of treatment effect or as proof that a treatment caused an event.

For other adverse events, the recorded counts are 17 of 47 for placebo, 19 of 47 for CAT-354 150 mg, 25 of 51 for CAT-354 300 mg, and 25 of 48 for CAT-354 600 mg. The record does not provide a statistical comparison for these counts. It also does not report the death counts. The death values are not reported in the registry record.

The listed serious-event terms include Asthma at 4.3%, and Cardio-respiratory arrest, Sinusitis, Contusion, Overdose, and Brain injury at 2.1% each. The record does not make clear in these entries how the terms relate to individual treatment groups, and the percentages should not be used to infer group-specific risks. Event counts and terms require context about seriousness criteria, severity, relatedness, timing, and participant-level overlap, which is not reported in the registry record.

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

The trial addresses a clinically relevant statistical question: whether mean asthma-control scores changed differently by Day 92 among adults assigned to placebo or to one of three CAT-354 regimens. Randomization and a concurrent placebo group are features that can support a comparative analysis, while the ACQ provides a defined participant-reported outcome. These design features explain what the study set out to assess; they do not reveal the result.

The central limitation for interpretation is that the registry record does not report the primary endpoint estimates or the uncertainty around them. It is therefore not possible to state how much scores changed in any arm, whether the groups differed, or how precise a treatment comparison was. The endpoint scale and schedule provide useful context, but they cannot substitute for observed results.

The safety entries provide descriptive counts for serious and other adverse events. They do not establish causality, and they do not encompass every aspect of safety assessment. The death values are not reported in the registry record. No conclusion about the overall balance of benefits and harms can be reached from these selected counts alone.

Secondary outcomes could add information about lung function, asthma control over time, rescue medication use, quality of life, and patient global impression. However, their names and measurement schedules do not show their results. The registry record lists many outcomes and analyses, but does not report the procedures used to address multiplicity. Any isolated secondary finding, if present in another source, would need to be interpreted in light of the full analysis plan and the number of comparisons.

The result does not establish that CAT-354 is effective or ineffective. Rather, the posted registry information documents the study question, treatment groups, endpoint definition, and selected safety counts while leaving the primary comparative outcome unreported. A reader can describe the design and what was measured, but cannot infer the missing treatment-effect estimate from enrollment, dose schedules, or safety counts.

13. Why This Trial Matters Statistically

This trial is statistically informative as an example of a multi-arm randomized study with a participant-reported continuous primary endpoint. It compares three dose regimens with placebo and defines asthma control using a structured questionnaire. That design creates a need to distinguish the primary comparison from the many secondary outcomes and analyses listed in the record.

The endpoint is a change from baseline, so its interpretation depends on both the starting measurement and follow-up measurement, along with the analysis population and handling of unavailable values. The record defines an evaluable population but does not provide the Day 92 group counts or missing-data approach. Those details are necessary to understand which participants contributed to the reported endpoint and how robust the estimate might be to incomplete follow-up.

Multiplicity is another statistical issue. The registry lists 16 outcome measures and 29 analyses. Without an identified hierarchy or adjustment procedure, readers cannot determine how the analysis plan controlled interpretation across the set of outcomes. This does not establish that any particular reported result would be misleading; it means that the relevant safeguards are not described in the registry record.

Finally, the record shows why protocol details and outcome estimates serve different purposes. The design and endpoint description explain what investigators intended to compare, while group estimates and uncertainty measures are needed to judge what the data show. Because the primary comparative results are not reported in the registry record, the study can be characterized methodologically, but its primary efficacy result cannot be reconstructed from the posted information.

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 registry record leaves important trial-specific information unavailable. It does not report the primary ACQ estimates by arm, the treatment contrasts, confidence intervals, p-values, or endpoint-specific sample sizes. Consequently, the magnitude and precision of the primary outcome cannot be evaluated. The record also does not state whether the reported primary analysis adjusted for baseline ACQ or used another model, and its detailed statistical analysis plan is not reported in the registry record.

The described evaluable population depends on treatment exposure and safety-related discontinuation. The record does not explain how participants outside that definition were handled, whether the population was specified before analysis, or whether a separate analysis based on randomized assignment was conducted. Participant flow by arm, reasons for missing Day 92 measurements, and methods for handling missing scores are not reported in the registry record.

Several outcome measures and analyses are listed, but the registry record does not describe a multiplicity strategy or provide enough information to identify a full prespecified hierarchy. It also does not report interim analyses, stopping rules, or the trial’s sample-size justification. The planning illustration described in the record is based on the observed effect and should not be mistaken for the original design rationale or for observed power.

Safety interpretation is limited to the posted counts and listed serious-event terms. The record does not report death counts, event relatedness, severity detail, timing, duration, or the method used to summarize recurrent events. The masking descriptions also differ: the title says double-blind, while the masking field says triple. The registry record does not explain that difference. These omissions limit independent assessment of the analysis and the completeness of the trial’s interpretation.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study to Evaluate the Safety and Efficacy of CAT-354 — NCT00873860.
• Registry record last updated 2017-03-24; status last verified 2017-02.
• Results first posted 2017-02-23.
• 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

NCT00873860 is a completed phase 2a randomized, placebo-controlled, parallel-arm study sponsored by MedImmune LLC. It enrolled 357 adults with uncontrolled, moderate-to-severe, persistent asthma and evaluated CAT-354 at 150 mg, 300 mg, and 600 mg against matched placebo. The listed injections were administered on Day 1, 15, 29, 43, 57, 71, and 85.

The primary endpoint was change from baseline in mean ACQ score at Day 92. The registry record describes the questionnaire, scale, and evaluable population, but does not report the primary endpoint results or the comparative estimate. It lists 16 outcome measures and 29 analyses, alongside descriptive serious and other adverse event counts. Death values, detailed analysis methods, missing-data procedures, and multiplicity handling are not reported in the registry record. The posted information therefore supports a description of the design and measures, but not a conclusion about the primary comparative result.