This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Safety and Efficacy of Multiple Doses of Canakinumab (ACZ885) in Chronic Obstructive Pulmonary Disease (COPD) Patients (NCT00581945), a randomized phase 1, phase 2 study. The primary outcome is Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1).
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00581945 |
| Phase | Phase 1, Phase 2 |
| Condition | Chronic Obstructive Pulmonary Disease |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Double |
| Enrollment | 147 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Novartis |
| Results posted | Yes |
2. Clinical Question
Population
Patients with chronic obstructive pulmonary disease were enrolled. The registry reports enrollment of 147 participants. For the primary outcome, the defined safety population consisted of randomized patients who received at least one dose of study drug; the registry does not separately report the size of that population for the FEV1 analysis.
Intervention
Canakinumab, also identified as ACZ885, was administered by intravenous infusion. The description begins with 1 mg/kg, followed four weeks later by 3 mg/kg and another 3 mg/kg two weeks later. It then describes 6 mg/kg doses every four weeks, but the canakinumab arm description is incomplete about when dosing ended.
Comparator
Participants in the comparison group received matching placebo by intravenous infusion at weeks 1, 5, 7, and thereafter every four weeks until the end of the 45-week treatment period.
Primary question
The primary outcome was change from baseline in forced expiratory volume in one second (FEV1), measured at Week 25 and Week 45. The clinical question was whether the recorded FEV1 changes differed between the canakinumab and placebo groups. The registry record does not report the group results or a between-group estimate, so the size and precision of any difference cannot be described.
3. Trial Design
The registry identifies this as a Phase 1 and Phase 2 study with randomized allocation, double masking, and a parallel-group model. It was described as exploratory and placebo controlled. Novartis is listed as the sponsor. The study status is completed; the recorded start was 2007-01, and primary completion was 2010-05.
Enrollment was 147. The intervention groups were canakinumab and placebo. The placebo description specifies matching intravenous infusions at weeks 1, 5, 7, and every four weeks thereafter through the 45-week treatment period. The canakinumab description specifies an initial 1 mg/kg dose, then 3 mg/kg doses at the stated later visits, followed by 6 mg/kg every four weeks. Its description ends before specifying the end of that dosing schedule, so the full schedule cannot be reconstructed from the registry record.
The primary outcome was a continuous measure: change from baseline in FEV1, reported as a mean with standard deviation. Measurements were planned at baseline, Week 25, and Week 45. The record also identifies a secondary outcome concerning participants who experienced serious adverse events or discontinued because of adverse events. It lists six outcome measures overall, but the names of the other measures are not reported in the registry record.
The record does not describe the randomization procedure, allocation concealment, masking procedures in operational detail, or how adherence to the assigned infusions was assessed. Those details should not be inferred from the design labels alone. Nor does the registry record report the trial's own sample-size justification.
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
| Stage | Canakinumab | Placebo |
|---|---|---|
| STARTED | 74 | 73 |
| COMPLETED | 65 | 63 |
| NOT COMPLETED | 9 | 10 |
Reasons for not completing this period:
| Reason | Canakinumab | Placebo |
|---|---|---|
| Adverse Event | 4 | 4 |
| Unsatisfactory therapeutic effect | 2 | 0 |
| Withdrawal by Subject | 2 | 6 |
| Death | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: The safety population consisted of all randomized patients who received at least one dose of the study drug.
5. Baseline Characteristics
The table reproduces the baseline characteristics posted in the registry, which describe the participants analysed at baseline and help show whether the randomized groups were comparable.
| Characteristic | Unit | Canakinumab | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 74 | 73 | 147 | |
| Age Continuous | years | 63.9 (SD 7.70) | 63.6 (SD 7.92) | 63.7 (SD 7.78) |
| Sex: Female, Male: Female | Participants | 28 | 31 | 59 |
| Sex: Female, Male: Male | Participants | 46 | 42 | 88 |
6. Primary Endpoint
The registry lists the primary outcome as Change From Baseline in Forced Expiratory Volume in 1 Second (FEV1), measured over Baseline, Week 25 and Week 45.
| Element | Registry entry |
|---|---|
| Result type | Mean |
| Measure of spread | Standard Deviation |
| Unit | Liters |
| Endpoint classification | Continuous Endpoint |
FEV1 is the amount of air a person can exhale in one second. In this study it was measured by spirometry, with visits scheduled at baseline, Week 25, and Week 45. The registry description says that testing was performed at approximately the same time of day at each visit to reduce diurnal variation, and that spirometry calibration and evaluation followed the stated American Thoracic Society and European Respiratory Society recommendations for acceptability.
The endpoint is expressed as change from baseline, rather than as a single follow-up measurement. This focuses attention on how the recorded measure changed over the study period. The registry description states that a positive change from baseline indicates improvement in lung function. Comparing changes between the randomized groups would address whether their observed trajectories differed, but the record does not report the group means, variability, or a comparative estimate at either follow-up.
General statistical context: FEV1 is continuous, so a group mean describes the central value while a standard deviation describes variation among individual measurements. A mean difference can be useful for comparing groups, but its precision also matters. The registry record does not report a confidence interval or other precision estimate for this endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The record establishes the study question and design, but it does not provide the primary FEV1 outcome results. It names change from baseline in FEV1 as the primary outcome and specifies baseline, Week 25, and Week 45 as the measurement time points. However, the registry record contains no group means, standard deviations, between-group contrasts, confidence intervals, or p-values for those measurements. The direction, magnitude, and precision of the primary comparison therefore cannot be assessed from the registry record.
The study enrolled 147 participants. The adverse-event information lists 74 participants at risk in the canakinumab group and 73 in the placebo group. Those safety counts do not establish the number included in an FEV1 analysis, and they should not be treated as the analyzed sample sizes for the primary endpoint. The record defines the safety population as randomized patients who received at least one dose, but does not report a separate primary-outcome analysis population or its size.
General statistical context: a group mean alone would not show how uncertain a comparison is. A confidence interval, when reported, describes a range of values compatible with the data under the analysis assumptions; it is not a guarantee that the true effect lies within that range. A p-value, when reported, addresses compatibility with a specified null model and does not quantify the clinical importance of an estimate. None of these statistics is reported for the primary FEV1 comparison in the registry record.
The record identifies the study as exploratory and includes multiple outcome measures and more than one FEV1 follow-up time. This makes a clearly specified analysis plan important for interpreting any reported comparisons. The registry record does not report a multiplicity strategy or a primary comparison that resolves the multiple time points into one result. It would therefore be inappropriate to select one visit or infer which comparison was intended to carry the principal statistical interpretation.
The available information supports a description of the planned question and some safety counts, not a conclusion about the primary lung-function result. It also does not establish why the study was stopped or whether every planned measure was collected. Those details are not reported in the registry record.
9. Statistical Methods Explained
General statistical context: the primary outcome is continuous because FEV1 is measured on a numerical scale. The registry identifies the reported summary as a mean and standard deviation. A mean gives a central summary of measurements in a group. A standard deviation describes how spread out individual values are around that mean. These summaries are not interchangeable: the mean concerns the group average, while the standard deviation concerns participant-to-participant variation.
Change from baseline is a within-participant quantity, but the clinical comparison of interest is between randomized groups. In general, an analysis may compare the average changes between groups or use a model that accounts for baseline and follow-up measurements. The registry record does not report which specific model or estimator was used, whether baseline values were adjusted for, or how repeated measurements were handled. Those choices affect the interpretation of an estimate, so none should be presumed.
FEV1 was measured at two follow-up visits, Week 25 and Week 45, in addition to baseline. General statistical context: when outcomes are observed repeatedly, an analysis can account for the fact that measurements from the same participant are related. Treating all measurements as independent would ignore that relationship. The registry record does not state whether a repeated-measures model, separate visit-specific comparisons, or another approach was used. It also does not report results for either visit.
A standard deviation describes spread, but it is not itself a measure of the uncertainty in a group mean or a between-group contrast. General statistical context: standard errors and confidence intervals are often used to express that uncertainty. A confidence interval can help readers judge both the range of plausible estimates and whether the data are precise enough to distinguish effects of different sizes. The registry record does not provide confidence intervals or standard errors for the primary endpoint.
General statistical context: a p-value is interpreted relative to a statistical model and a null hypothesis. It does not indicate the probability that a treatment is effective, and it does not measure the size or practical importance of a difference. No p-value or named statistical test for the primary FEV1 outcome is reported in the registry record. The record also does not report whether analyses were adjusted for baseline characteristics or other covariates.
The study is described as randomized, double-blind, and parallel group. General statistical context: random allocation is intended to make assigned groups comparable, on average, with respect to factors that could influence outcomes. Masking can reduce the influence of knowledge of assignment on participant behavior, care, or outcome assessment. These design features do not remove the need to report how assignment and masking were implemented or how outcomes were analyzed. Those operational details are not reported in the registry record.
The registry record lists six outcome measures, but only the primary FEV1 outcome and a secondary outcome concerning serious adverse events or discontinuation due to adverse events are identified in the registry entries. Having multiple outcomes can raise multiplicity questions. General statistical context: when many comparisons are made, the chance of at least one apparently unusual result can increase unless the analysis plan addresses that issue. No multiplicity adjustment or hierarchy among outcomes is reported in the registry record.
The planning assumptions described for sample-size illustrations are a two-sided significance level of 0.05, equal allocation between the two groups, and a normal approximation. The illustrations are described as using a fraction of an observed effect. General statistical context: such calculations depend on the effect size chosen and other assumptions, and are planning tools rather than evidence about what happened in the trial. They are not observed power. The registry record does not report the trial's own sample-size justification, and without the primary outcome estimates, the observed effect cannot be evaluated from the registry information.
General statistical context: over-dispersion matters when observed variability exceeds what a chosen statistical model expects, because standard errors and test results from an unsuitable model may be misleading. The record does not indicate that over-dispersion was assessed or relevant to the FEV1 analysis. Since FEV1 is continuous and the analysis model is not reported, no specific model issue can be established.
10. Multiplicity, Missing Data and Analysis Populations
The registry record lists six outcome measures and identifies FEV1 change at Week 25 and Week 45 as the primary outcome timeframe. It also identifies a secondary outcome concerning serious adverse events or discontinuation due to adverse events. The remaining outcome names are not reported in the registry record. The primary outcome has multiple time points and is not reduced in the registry record to one reported comparison.
General statistical context: multiple outcomes, visits, or analyses can create multiplicity. A prespecified testing strategy can clarify which comparisons are primary and how the overall risk of false-positive findings is handled. The registry record does not report such a strategy, any multiplicity adjustment, or an ordered testing plan. No interim analyses or stopping rules are reported in the registry record.
The registry record does not report how missing FEV1 measurements were handled, whether any participants withdrew, or whether the analysis used imputation, complete cases, or another approach. These omissions matter because missing measurements can affect both the analyzed group and the interpretation of change over time. No reason for missingness or sensitivity analysis is reported.
The record defines the safety population as all randomized patients who received at least one dose of study drug. It does not report the population used for the primary efficacy analysis, the number included at each visit, or whether participants were analyzed according to randomized assignment. Those analysis-population details are not reported in the registry record.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Canakinumab | 23 | 74 | 31.1% |
| Placebo | 14 | 73 | 19.2% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 5% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Canakinumab | 59 of 74 |
| Placebo | 51 of 73 |
Most frequent serious adverse event terms
| Event term | Organ system | Canakinumab | Placebo |
|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 9 of 74 | 7 of 73 |
| Pneumonia | Infections and infestations | 4 of 74 | 3 of 73 |
| Coronary artery disease | Cardiac disorders | 1 of 74 | 1 of 73 |
| Chest pain | General disorders | 1 of 74 | 1 of 73 |
| Bronchitis | Infections and infestations | 2 of 74 | 0 of 73 |
| Bronchopulmonary aspergillosis | Infections and infestations | 2 of 74 | 0 of 73 |
| Staphylococcal infection | Infections and infestations | 2 of 74 | 0 of 73 |
| Benign prostatic hyperplasia | Reproductive system and breast disorders | 2 of 74 | 0 of 73 |
| Acute respiratory failure | Respiratory, thoracic and mediastinal disorders | 1 of 74 | 1 of 73 |
| Acute myocardial infarction | Cardiac disorders | 0 of 74 | 1 of 73 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Canakinumab | Placebo |
|---|---|---|---|
| Chronic obstructive pulmonary disease | Respiratory, thoracic and mediastinal disorders | 38 of 74 | 36 of 73 |
| Pyrexia | General disorders | 7 of 74 | 7 of 73 |
| Cough | Respiratory, thoracic and mediastinal disorders | 8 of 74 | 6 of 73 |
| Upper respiratory tract infection | Infections and infestations | 9 of 74 | 4 of 73 |
| Nausea | Gastrointestinal disorders | 5 of 74 | 6 of 73 |
| Sinusitis | Infections and infestations | 6 of 74 | 5 of 73 |
| Diarrhoea | Gastrointestinal disorders | 5 of 74 | 5 of 73 |
| Back pain | Musculoskeletal and connective tissue disorders | 5 of 74 | 4 of 73 |
| Urinary tract infection | Infections and infestations | 4 of 74 | 4 of 73 |
| Oral candidiasis | Infections and infestations | 3 of 74 | 4 of 73 |
Serious events with the highest arm-level rate: chronic obstructive pulmonary disease (12.2%), pneumonia (5.4%), bronchitis (2.7%), bronchopulmonary aspergillosis (2.7%), staphylococcal infection (2.7%).
The adverse-event record lists 23 of 74 participants in the canakinumab group and 14 of 73 in the placebo group as affected by serious adverse events. For other adverse events, the listed counts are 59 of 74 and 51 of 73, respectively. These are descriptive counts in the registry record; they do not by themselves establish a causal relationship or explain the severity, timing, or duration of events.
The record lists chronic obstructive pulmonary disease at 12.2%, pneumonia at 5.4%, and bronchitis, bronchopulmonary aspergillosis, staphylococcal infection, and benign prostatic hyperplasia at 2.7% each among the serious adverse-event terms. The denominator and detailed event-counting context for those percentages are not reported in the registry record. Death counts are not reported.
General statistical context: safety counts are most informative when read with clear definitions, exposure duration, follow-up, and event-level detail. The record does not provide enough detail to infer comparative risks from these counts alone. The secondary outcome also includes discontinuation due to adverse events, but separate discontinuation counts are not reported in the registry record.
12. What the Result Does, and Does Not, Mean
The registry record describes an exploratory randomized comparison of intravenous canakinumab and placebo in patients with chronic obstructive pulmonary disease. Its primary question concerned change from baseline in FEV1 at Week 25 and Week 45. The record does not report the primary outcome values or an analysis comparing the groups. Consequently, it cannot establish the direction, magnitude, or precision of the observed FEV1 comparison.
The reported safety information gives counts of participants affected by serious and other adverse events in each group and lists several serious adverse-event terms. These data are descriptive. Without further event details and an analysis, they do not establish whether an event was caused by study drug or quantify the uncertainty around a comparative safety estimate. Death counts are not reported in the registry record.
General statistical context: an estimate and its uncertainty are both important when interpreting a clinical comparison. A small or imprecise estimate may be compatible with a range of possible effects, while a precise estimate can still be judged differently depending on the clinical question. The registry record does not provide the primary estimate or its uncertainty, so this interpretation cannot be made for FEV1.
The study's exploratory designation and its multiple outcomes and visits are relevant to interpretation. The registry record does not report a multiplicity plan, analysis populations for efficacy, or missing-data methods. It also does not report the trial's own sample-size justification. These gaps prevent reconstruction of the inferential plan and constrain conclusions to what the registry actually records.
Thus, the record supports an account of the study design, the primary measure, and selected safety counts, but not a conclusion about the comparative primary outcome. It should not be read as evidence that the groups were equivalent, or that a difference was present: neither statement can be assessed from the primary results reported in the registry record.
13. Why This Trial Matters Statistically
This study raises several statistical interpretation issues that are common in clinical research. The primary endpoint is a continuous physiological measure, recorded at multiple visits and summarized by means and standard deviations. A careful comparison needs more than a description of the measure: readers also need the group estimates, a clear contrast, and information about the uncertainty of that contrast. Those primary results are not reported in the registry record.
The design is identified as randomized, double-blind, and parallel group, which establishes the broad framework for the comparison. But design labels do not substitute for details of the analysis. The registry record does not describe the primary analysis method, the efficacy analysis population, or the handling of missing measurements. These omissions make it difficult to determine exactly how the planned question would be answered statistically.
The record also lists multiple outcomes and FEV1 follow-up times. General statistical context: when several results could be emphasized, a prespecified hierarchy or multiplicity approach helps readers distinguish confirmatory findings from exploratory comparisons. No such approach is reported in the registry record. This is especially relevant because the study is explicitly described as exploratory.
The safety information illustrates a separate point: counts can describe recorded events, but interpretation depends on definitions, follow-up, and event detail. The registry reports serious and other adverse-event counts, while some contextual details, including deaths and separate discontinuations due to adverse events, are not reported.
These features make the record useful for understanding the question and design, while also demonstrating why outcome estimates and transparent analysis details are essential for statistical interpretation. The absence of primary results is a limit on what can be concluded, not a result in favor of either group.
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.
A central limitation of the registry record is that it does not report the primary FEV1 results. There are no group means or standard deviations at the stated visits, no between-group comparison, and no precision estimate. The primary outcome therefore cannot be interpreted quantitatively from the registry record.
The analysis methods are not described. The record does not identify the statistical model, any covariate adjustment, the efficacy analysis population, or the method for handling repeated measurements. It also does not report missing-data methods, participant counts for the primary endpoint at each visit, or sensitivity analyses. These limitations prevent assessment of how departures from the planned data structure may have affected the analysis.
The record lists six outcome measures and two FEV1 follow-up visits, but does not report a multiplicity strategy. The names of the other outcome measures are not reported in the registry record. No interim analyses or stopping rules are reported, and the trial's own sample-size justification is not reported.
The intervention description is incomplete: it ends after stating that canakinumab was given at 6 mg/kg every four weeks, without specifying when that schedule ended. The placebo description does identify a 45-week treatment period. This difference in the completeness of arm descriptions limits reconstruction of the dosing schedule from the registry record.
For safety, the record lists affected-participant counts and several serious adverse-event terms, but does not report deaths, separate discontinuation counts, or the denominator and detailed context for the listed event percentages. These omissions limit interpretation of the safety data beyond the descriptive figures recorded.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Safety and Efficacy of Multiple Doses of Canakinumab (ACZ885) in Chronic Obstructive Pulmonary Disease (COPD) Patients — NCT00581945.
- Registry record last updated 2011-06-30; status last verified 2011-06.
- Results first posted 2011-06-27.
- Data retrieved from ClinicalTrials.gov on 2026-11-09.
- Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.
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18. Record Summary
NCT00581945 is a completed randomized, double-blind, parallel-group, placebo-controlled exploratory study listed as Phase 1 and Phase 2. It enrolled 147 patients with chronic obstructive pulmonary disease and compared intravenous canakinumab with matching placebo. The recorded start was 2007-01, and primary completion was 2010-05.
The primary outcome was change from baseline in FEV1 at Week 25 and Week 45. Although the record describes the measurement and its interpretation, it does not report the primary results or a statistical comparison. It lists six outcome measures and a secondary safety outcome concerning serious adverse events or discontinuation due to adverse events.
Serious adverse events were recorded for 23 of 74 participants in the canakinumab group and 14 of 73 in the placebo group; other adverse events were recorded for 59 of 74 and 51 of 73, respectively. The registry record does not report the primary analysis methods, missing-data handling, multiplicity strategy, or trial-specific sample-size justification.