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 Clazakizumab (Anti-Interleukin 6 (IL-6) Monoclonal) Compared to Placebo for Coronavirus Disease 2019 (COVID-19) (NCT04348500), a randomized phase 2 study. The primary outcome is Safety of Clazakizumab for the Treatment of Patients With COVID-19 Disease.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04348500 |
| Phase | Phase 2 |
| Condition | COVID-19 |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 17 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Cedars-Sinai Medical Center |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned patients with COVID-19 and signs of pulmonary involvement who had not yet required mechanical ventilation or extracorporeal membrane oxygenation (ECMO). The summary describes a single-center exploratory phase II study. The primary-outcome population is described as enrolled patients who received the initial dose of the investigational product.
Intervention
Participants assigned to clazakizumab received 25 mg in 50 mL of 0.9% saline by intravenous infusion over 30 minutes as a single dose. The registry summary also describes the possibility of open-label clazakizumab for patients who deteriorated or progressed to mechanical ventilation or ECMO, subject to the stated conditions and investigator or treating-physician discretion.
Comparator
The placebo was 50 mL of 0.9% saline, given by intravenous infusion over 30 minutes as a single dose. The study is listed as randomized, quadruple-masked and parallel-group; the brief summary describes it as double-blind and placebo-controlled.
Primary question
The primary outcome concerns the number of severe adverse events during 14 days that were unusual, unexpected, or assessed as related to the investigational product. The registry record does not report the arm-specific number meeting that specific definition or a statistical comparison of the primary outcome. The posted serious-adverse-event counts are relevant safety information, but do not by themselves establish the result for the narrower primary-outcome definition.
3. Trial Design
This is a phase II randomized, parallel-group trial of clazakizumab versus placebo for COVID-19. The registry lists quadruple masking, while the brief summary calls the study double-blind. The study is described as single-center and exploratory in the summary. The registry lists 17 participants enrolled and a completed status. The planned enrollment described in the summary was 60; the registry record does not explain the difference between that planned figure and the enrollment listing.
The clazakizumab arm received 25 mg in 50 mL of 0.9% saline by intravenous infusion over 30 minutes. The placebo arm received 50 mL of 0.9% saline by intravenous infusion over 30 minutes. The summary describes an option for open-label clazakizumab 25mg IV x 1 dose if a participant progressed to mechanical ventilation or ECMO, or developed clinical signs of deteriorating COVID-19 disease, provided there were no treatment-related serious adverse events and the investigator or treating physician chose to give it. The dose could be given within the initial 14-day period after the first dose, with a minimum of 24 hours between doses. The participant remained blinded to the identity of the first dose.
The listed primary outcome is a safety measure over 14 days. Listed secondary outcomes include survival at 28 days and 60 days, use of open-label clazakizumab, days in intensive care and hospital, and need for mechanical ventilation or ECMO. The registry records 7 outcome measures and 2 analyses. Details such as the randomization procedure, allocation concealment, planned analysis methods and sample-size justification 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.
Before assignment: Of the total 105 participants ages 18 years and older screened, 17 were enrolled in this single center, randomized, double-blind, placebo-controlled, exploratory phase II study.
Overall Study
| Stage | Clazakizumab | Placebo |
|---|---|---|
| STARTED | 8 | 9 |
| Treated | 8 | 8 |
| COMPLETED | 6 | 6 |
| NOT COMPLETED | 2 | 3 |
Reasons for not completing this period:
| Reason | Clazakizumab | Placebo |
|---|---|---|
| Death | 2 | 2 |
| Withdrawn by subject due to dementia | 0 | 1 |
Analysis population for the primary outcome, as defined in the registry: Enrolled patients who received the initial dose of the IP were analyzed.
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: Enrolled patients who received the initial dose of the IP were analyzed.
| Characteristic | Unit | Clazakizumab | Placebo | Total |
|---|---|---|---|---|
| Participants analysed | 8 | 8 | 16 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 6 | 4 | 10 |
| Age, Categorical: >=65 years | Participants | 2 | 4 | 6 |
| Age, Continuous | years | 59 (SD 13.44) | 60 (SD 13.14) | 59 (SD 13.86) |
| Sex: Female, Male: Female | Participants | 3 | 3 | 6 |
| Sex: Female, Male: Male | Participants | 5 | 5 | 10 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 3 | 5 | 8 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 5 | 3 | 8 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Asian | Participants | 2 | 0 | 2 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Black or African American | Participants | 1 | 1 | 2 |
| Race (NIH/OMB): White | Participants | 5 | 7 | 12 |
| Race (NIH/OMB): More than one race | Participants | 0 | 0 | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 | 0 | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Safety of Clazakizumab for the Treatment of Patients With COVID-19 Disease, measured over 14 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | Adverse Events |
| Endpoint classification | not reduced to a single comparison |
The primary outcome is defined as the number of severe adverse events during 14 days that are unusual, unexpected, or assessed as related to the investigational product. It is a count-based safety outcome, not a measure of symptom improvement, survival, or time to recovery. The outcome population is described as enrolled patients who received the initial dose.
Counting specified adverse events can help describe potential safety concerns observed during a defined follow-up period. The definition in this trial combines several criteria: an event must be severe and also unusual, unexpected, or assessed as related to the investigational product. Those criteria matter when interpreting the result. A count of all serious adverse events is not automatically the same as a count meeting this primary definition. The registry record does not report the arm-specific primary-outcome counts, how the criteria were applied, or a statistical comparison for this endpoint.
In general, a count outcome can be summarized by the number of affected participants or by the total number of events; those quantities can differ if a participant experiences more than one event. The registry record does not clarify which interpretation applies to the primary outcome’s word “number.” Nor does it report a detailed event-adjudication process. The posted safety figures should therefore be read as reported event summaries rather than as a complete, fully specified estimate of the primary endpoint.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record reports safety counts for the clazakizumab and placebo groups. Each group lists 8 participants at risk for serious adverse events, with 2 affected in the clazakizumab group and 3 in the placebo group. For other adverse events, each group lists 8 at risk, with 2 affected in each group. Deaths are listed as 2 in each group. These are descriptive counts; the registry record does not report confidence intervals, p-values, or an inferential comparison for these figures.
These serious-adverse-event counts should not be treated as the result for the primary outcome without qualification. The primary outcome is restricted to severe adverse events that are unusual, unexpected, or assessed as related to the investigational product. The posted group counts do not identify which events met those criteria. The registry record does not report the primary-outcome count separately by group, so the primary safety question cannot be resolved from the event counts alone.
The record lists serious-event terms and percentages: Death, 25.0%; Candida parapsilosis Fungemia, 12.5%; Hypoxic Respiratory Failure, 12.5%; Multidrug-Resistant (MDR) Pseudomonas, 12.5%; Pulseless Electrical Activity (PEA) Event, 12.5%; and T12 Compression Fracture Secondary to Fall, 12.5%. These are reported event terms, not an adjusted comparison between randomized groups. The record does not specify whether the percentages represent participants or events, whether terms can overlap within a participant, or how the listed terms relate to the primary-outcome criteria.
The enrollment listing is 17, while each adverse-event group reports 8 participants at risk. The registry record does not explain this accounting or identify the disposition of any participant not represented in those group figures. That limits interpretation of the safety denominators and makes it important not to assume that the reported group counts cover every enrolled participant.
Small descriptive counts can be difficult to interpret because they may be imprecise and sensitive to individual events. In general, a confidence interval communicates uncertainty around an estimate, while a statistical comparison addresses compatibility with a specified null hypothesis under stated assumptions. Neither is reported for these adverse-event counts. The record also does not report a model or adjustment method for comparing groups. The posted data therefore describe observed safety events but do not establish a precise comparative effect.
The summary describes open-label clazakizumab as an option following deterioration or progression, subject to clinical conditions and investigator or treating-physician discretion. Because use of that treatment could occur after the randomized first dose, it is relevant context for later outcomes. The number of participants who received the open-label dose is not reported in the registry record. The listed outcomes for survival, hospital and intensive-care duration, and respiratory support also lack result values in the record, so they cannot be interpreted as comparative findings.
9. Statistical Methods Explained
Randomization is intended to assign participants to study groups by chance, reducing systematic differences in prognostic characteristics on average. It does not guarantee that groups will be identical, particularly in a small study. The registry lists this study as randomized and parallel-group, but the randomization sequence, allocation procedure and concealment details are not reported in the registry record. Without those details, the method of assignment cannot be assessed beyond the listed design.
What does masking contribute?
Masking is intended to limit the influence of knowledge about assigned treatment on care, outcome assessment, and reporting. The registry lists quadruple masking, while the brief summary describes a double-blind study. The record does not identify which people are included in the quadruple-masking description or explain the difference between these descriptions. The placebo and active infusion descriptions are similar in volume and administration, but the registry record does not state whether masking was successfully maintained.
How should a count outcome be read?
The primary outcome is a count of specified severe adverse events within 14 days. In general, a count can refer to events or to participants with at least one event. If a participant can have multiple events, the event total and the number of affected participants need not be the same. The registry record does not give further detail on the counting convention for the primary endpoint. The adverse-event group figures separately report participants at risk and participants affected, but those figures do not supply the primary endpoint counts under its specific criteria.
In general, count data may be analyzed with methods that account for the discreteness of counts. Some count distributions allow more variability than a simple Poisson model would expect; this is called over-dispersion. When over-dispersion is present, a model that assumes less variability may produce uncertainty estimates that are too narrow. Whether over-dispersion was assessed or addressed in this trial is not reported in the registry record. No model for the primary outcome is reported there.
What does an uncertainty interval tell the reader?
In general, a confidence interval gives a range of values compatible with the data and the method used to calculate it. Its width reflects statistical precision: wider intervals indicate greater uncertainty, while narrower intervals indicate greater precision under the method’s assumptions. A confidence interval does not by itself establish that a treatment caused an observed difference, and interpretation also depends on the study design and analysis. The registry record does not report confidence intervals for the posted safety counts.
A p-value, in general, describes how compatible data are with a specified null hypothesis under a statistical model; it is not the probability that the null hypothesis is true. Its interpretation depends on the prespecified analysis and assumptions. The record does not report a p-value for the primary endpoint or for the adverse-event group counts. A numerical difference between descriptive counts, without an uncertainty estimate or stated comparison method, should not be presented as an inferential treatment effect.
What is known about sample-size planning?
The registry summary describes planned enrollment of 60, whereas the enrollment listing is 17. The registry record does not report the trial’s sample-size justification or explain the enrollment difference. A separate planning illustration uses a two-sided significance level of 0.05, equal allocation between groups, a normal approximation, and fractions of the observed effect as planning targets. Such calculations are planning illustrations, not observed power and not evidence that the study had adequate power for a particular clinical or safety question. The record does not report the trial’s own planned statistical assumptions in sufficient detail to treat the illustration as its design rationale.
In general, power is the probability that a specified analysis will reject a null hypothesis when a particular effect is true, under the assumptions used for planning. It is not a measure of how likely a finding is to be true. Calculating power after a study from its observed effect does not establish the study’s ability to detect other effects. For a small exploratory study, estimates and their uncertainty are more informative than a retrospective power label. No inferential estimates for the primary outcome are reported in the registry record.
How do secondary outcomes fit the analysis?
The registry lists outcomes for survival at 28 days and 60 days, open-label clazakizumab use, intensive-care and hospital days, and need for mechanical ventilation or ECMO. These outcomes represent different types of data and may require different analytical approaches. Time-to-event outcomes, counts, and durations do not have interchangeable interpretations. The analysis methods and results for these outcomes are not reported in the registry record.
In general, prespecified methods help readers understand how outcomes were defined, which participants were included, and how missing values and multiple comparisons were handled. The registry record does not report the detailed statistical analysis plan, model specifications, or uncertainty estimates needed to evaluate those choices. The design listing and outcome definitions describe the study’s broad structure, but they do not substitute for those analysis details.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists 7 outcome measures and 2 analyses. The listed outcomes include the primary safety outcome and secondary measures covering survival, open-label dosing, duration of intensive-care and hospital stays, and respiratory support. When a study examines multiple outcomes or makes multiple comparisons, the chance of at least one apparently notable result can increase. In general, multiplicity procedures can control or describe that issue, but the appropriate approach depends on the questions and analysis plan. A multiplicity strategy is not reported in the registry record.
Missing-data methods and the amount or pattern of missing outcome data are also not reported in the registry record. Without that information, readers cannot determine how incomplete follow-up was handled or whether the analysis depended on assumptions about unavailable outcomes. The record describes the primary-outcome population as enrolled patients who received the initial dose, but does not state whether an intention-to-treat population was used for other outcomes or give detailed analysis-population definitions.
The safety groups each list 8 participants at risk, while the enrollment listing is 17. The registry record does not explain the difference or report whether any participants lacked safety follow-up, were excluded from a particular analysis, or had missing data. Those possibilities should not be assumed; the accounting is simply not reported. The record also does not describe interim analyses, stopping rules, or the statistical analysis plan. Those 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 |
|---|---|---|---|
| Clazakizumab | 2 | 8 | 25.0% |
| Placebo | 3 | 8 | 37.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Clazakizumab | 2 of 8 |
| Placebo | 2 of 8 |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 1% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Clazakizumab | 2 of 8 |
| Placebo | 2 of 8 |
Most frequent serious adverse event terms
| Event term | Organ system | Clazakizumab | Placebo |
|---|---|---|---|
| Death | General disorders | 2 of 8 | 2 of 8 |
| Worsening Kidney Function | Renal and urinary disorders | 1 of 8 | 1 of 8 |
| Candida parapsilosis Fungemia | Infections and infestations | 1 of 8 | 0 of 8 |
| Hypoxic Respiratory Failure | Respiratory, thoracic and mediastinal disorders | 0 of 8 | 1 of 8 |
| Multidrug-Resistant (MDR) Pseudomonas | Infections and infestations | 1 of 8 | 0 of 8 |
| Pulseless Electrical Activity (PEA) Event | Cardiac disorders | 0 of 8 | 1 of 8 |
| T12 Compression Fracture Secondary to Fall | Injury, poisoning and procedural complications | 0 of 8 | 1 of 8 |
| Worsening Hypoxia | General disorders | 1 of 8 | 0 of 8 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Clazakizumab | Placebo |
|---|---|---|---|
| Acute Kidney Injury (AKI) | Renal and urinary disorders | 0 of 8 | 1 of 8 |
| Delirium, multifactorial | Nervous system disorders | 0 of 8 | 1 of 8 |
| Enterococcus faecalis Bacteremia | Infections and infestations | 1 of 8 | 0 of 8 |
| Intermittent Atrial Fibrillation (AFib) with Labile Blood Pressure | Cardiac disorders | 0 of 8 | 1 of 8 |
| Methicillin-susceptible staphylococcus aureus (MSSA) Bacteremia | Infections and infestations | 0 of 8 | 1 of 8 |
| Paritonsillar Cellulitis | Infections and infestations | 1 of 8 | 0 of 8 |
| Respiratory Pseudomonas | Infections and infestations | 1 of 8 | 0 of 8 |
| Thrombocytopenia | Blood and lymphatic system disorders | 0 of 8 | 1 of 8 |
Serious events with the highest arm-level rate: death (25.0%), candida parapsilosis fungemia (12.5%), hypoxic respiratory failure (12.5%), multidrug-resistant (mdr) pseudomonas (12.5%), pulseless electrical activity (pea) event (12.5%).
The adverse-event record lists 8 participants at risk for serious adverse events in each group. It reports 2 affected in the clazakizumab group and 3 in the placebo group. For other adverse events, it lists 8 at risk in each group and 2 affected in each. Deaths are listed as 2 in each group. These are counts as recorded, not estimates adjusted for other factors.
The serious-event terms include Death at 25.0%, and Candida parapsilosis Fungemia, Hypoxic Respiratory Failure, Multidrug-Resistant (MDR) Pseudomonas, Pulseless Electrical Activity (PEA) Event, and T12 Compression Fracture Secondary to Fall, each at 12.5%. The registry record does not explain whether these percentages refer to participants or events, or whether a participant may contribute more than one term. The term list should not be read as a comparison between treatment groups.
The primary outcome has a narrower definition than the general serious-adverse-event figures: it counts severe events that were unusual, unexpected, or assessed as related to the investigational product during 14 days. The record does not report which listed events met those criteria or give the group-specific primary-outcome counts. The serious-event summaries are therefore useful descriptive safety information, but they do not establish the primary endpoint result or a causal treatment effect.
12. What the Result Does, and Does Not, Mean
The registry record documents a randomized phase II study and reports descriptive safety counts for the two groups. It also defines a 14-day primary safety outcome and lists secondary outcomes of interest. These details show what the study was designed to examine and what adverse-event summaries were posted. They do not, on their own, provide a complete comparative analysis.
The posted serious-adverse-event counts are 2 affected participants in the clazakizumab group and 3 in the placebo group, with 8 participants at risk in each. The other-adverse-event counts are 2 in each group, and deaths are listed as 2 in each group. Those figures describe the record’s reported counts. They do not establish that any observed difference is statistically reliable, nor do they establish that the groups had equivalent safety outcomes.
The primary endpoint specifically concerns severe events that were unusual, unexpected, or assessed as related to the investigational product. The registry record does not report the separate count meeting that definition in each group or a statistical analysis of it. It is therefore not possible to infer the primary endpoint’s comparative result from the general serious-adverse-event counts. The record also does not report confidence intervals or p-values for those counts.
In general, a randomized comparison can support causal interpretation when allocation, follow-up, outcome measurement, and analysis are suitably conducted. That interpretation still depends on study size, missing data, adherence, analysis choices, and precision. Details about several of those factors are not reported in the registry record. The gap between the planned enrollment described in the summary and the enrollment listing, as well as the safety-group accounting, also remains unexplained in the record.
The record does not provide results for the listed survival, open-label dosing, hospital duration, intensive-care duration, or respiratory-support outcomes. Nor does it report enough detail to assess multiplicity or missing-data handling. Accordingly, the posted information supports a description of the study design and the recorded adverse-event summaries, but not a definitive conclusion about comparative safety or other clinical outcomes.
13. Why This Trial Matters Statistically
This trial is statistically relevant because it illustrates the difference between an outcome definition and a broad adverse-event summary. The primary outcome is not simply every serious adverse event: it is restricted to severe events that were unusual, unexpected, or assessed as related to the investigational product. A group-level count of serious events cannot substitute for endpoint-specific counts when the criteria differ or are not mapped to individual events.
The registry also presents an important denominator question. It lists 17 participants enrolled, while the safety groups each list 8 participants at risk. The record does not explain this accounting. Clear reporting of who entered each analysis and how follow-up was handled is essential for interpreting event counts, especially when the study is small.
In general, small studies often yield estimates with substantial uncertainty, and a lack of a reported statistically significant difference would not prove that groups are equivalent. Here, the record does not report a primary-endpoint comparison, confidence intervals, or p-values. That makes it especially important to distinguish descriptive counts from inferential evidence rather than treating the observed counts as a complete treatment comparison.
The trial also makes visible how an open-label option can complicate interpretation of outcomes after randomization. The summary describes possible open-label clazakizumab following deterioration or progression, under specified conditions and at clinician discretion. The number of participants who received it is not reported in the registry record. Such post-randomization treatment is relevant context for later outcomes, but its impact cannot be assessed without the corresponding data and analysis.
Finally, the difference between planned enrollment in the summary and the enrollment listing, along with the unreported analysis plan and missing-data methods, emphasizes why transparent reporting matters. These are not reasons to dismiss the posted data; they define the limits of what the record can support.
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 has limited detail for evaluating the primary endpoint. It defines the 14-day outcome but does not report the arm-specific counts meeting the definition, the event-level application of its criteria, or an inferential comparison. The posted serious-adverse-event figures cannot be assumed to match that endpoint.
The summary describes planned enrollment of 60, while the enrollment listing is 17. The record does not explain why those figures differ. It also lists 8 participants at risk in each safety group, without explaining how those denominators relate to the enrollment listing. This leaves the safety-population accounting unclear.
The study is described as single-center and exploratory. Its completed status is listed, but the record does not report the detailed analysis plan, sample-size justification, randomization procedure, allocation concealment, missing-data approach, multiplicity strategy, or interim-analysis details. It does not report confidence intervals or p-values for the safety counts. These omissions limit assessment of precision, robustness, and the extent to which the posted analyses follow a prespecified plan.
The registry lists secondary outcomes, but their results are not reported in the record. The number receiving open-label clazakizumab is also not reported. The serious-event terms and percentages lack an explanation of the percentage denominator and possible overlap between terms. Together, these limitations mean the posted information is best treated as a partial descriptive record rather than a complete comparative account of trial outcomes.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Clazakizumab (Anti-Interleukin 6 (IL-6) Monoclonal) Compared to Placebo for Coronavirus Disease 2019 (COVID-19) — NCT04348500.
- Registry record last updated 2024-02-08; status last verified 2024-02.
- Results first posted 2021-12-02.
- 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
NCT04348500 is listed as a completed phase II randomized, parallel-group study of clazakizumab versus placebo for COVID-19. The registry lists quadruple masking; the brief summary describes the study as double-blind, single-center, placebo-controlled, and exploratory. The enrollment listing is 17, while the summary describes a planned enrollment of 60.
The primary outcome concerns severe adverse events during 14 days that are unusual, unexpected, or assessed as related to the investigational product. The record describes the primary-outcome population as enrolled patients who received the initial dose. Safety summaries list serious adverse events, other adverse events, deaths, and serious-event terms, but do not report a separate arm-specific result for the primary endpoint or an inferential comparison. The record also lists survival, open-label dosing, hospital and intensive-care duration, and respiratory-support outcomes; their results are not reported in the registry record.