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 A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab (TCZ) Administered to Participants With Giant Cell Arteritis (GCA). (NCT03923738), a na phase 1 study. The primary outcome is Maximum Serum Concentration (Cmax) of TCZ.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT03923738 |
| Phase | Phase 1 |
| Condition | Giant Cell Arteritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 24 |
| Arms in the primary outcome | n/a |
| Lead sponsor | Hoffmann-La Roche |
| Results posted | Yes |
2. Clinical Question
Population
Participants with giant cell arteritis (GCA) were eligible for the study. The registry record reports 24 enrolled participants. The pharmacokinetic population was defined as participants who received one dose of tocilizumab (TCZ) and had one valid pharmacokinetic sample; participants in that population were grouped according to treatment received. The number in this defined population is not reported in the registry record.
Intervention
The study evaluated TCZ administered by intravenous infusion every 4 weeks (Q4W). Its arm description says participants could receive up to 6 doses of Dose 1, followed by up to 6 doses of Dose 2. The registry identifies dose-level groups of TCZ IV 7 mg/kg Q4W and TCZ IV 6 mg/kg Q4W.
Comparator
There was no randomized control group: allocation is listed as not applicable, masking as none, and the model as single group. The two dose-level entries therefore should not be read as a like-for-like randomized comparison. The registry description presents sequential dose exposure, not a separate control treatment.
Primary question
The primary endpoint was maximum serum concentration (Cmax) of TCZ, measured in ug/mL. The registry lists the median and full range at baseline and Weeks 4, 8, 12, and 16-24. This endpoint concerns drug concentration over the stated assessment times. Numerical Cmax results are not reported in the registry record, so the degree of exposure and its variability cannot be described from this record.
3. Trial Design
This was a Phase Ib, open-label, dose-ranging study of TCZ given by intravenous infusion to patients with GCA. The registry lists the study as completed, with 24 participants enrolled. Its dates are 2019-08-05 for study start and 2020-11-12 for primary completion. These record details describe the study’s timing and size; they do not establish how many participants contributed to each endpoint.
The design is listed as single group, with allocation not applicable and no masking. The treatment description specifies up to 6 doses of Dose 1 of TCZ IV Q4W, followed by up to 6 doses of Dose 2 of TCZ IV Q4W. The registry also lists dose-level safety groups for TCZ IV 7 mg/kg Q4W and TCZ IV 6 mg/kg Q4W. Because this is not a randomized comparison, those groups should not be interpreted as independent, balanced treatment arms or as a randomized estimate of a dose effect.
The stated focus was pharmacokinetics, pharmacodynamics, and safety. The primary outcome was maximum serum TCZ concentration. Listed secondary outcomes included serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), and C-reactive protein (CRP), as well as erythrocyte sedimentation rate (ESR). The registry record does not report a statistical analysis plan, allocation details beyond not applicable, or an explanation of the sample-size rationale. It also does not report numerical results for the primary endpoint in the registry record 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: Participants from Period 1 (n=24) that completed the Period and reached remission entered Period 2 (n=22). Two participants withdrew prior to entering Period 2.
Period 1
| Stage | TCZ IV Q4W |
|---|---|
| STARTED | 24 |
| COMPLETED | 22 |
| NOT COMPLETED | 2 |
Reasons for not completing this period:
| Reason | TCZ IV Q4W |
|---|---|
| Adverse Event | 1 |
| Withdrawal by Subject | 1 |
Period 2
| Stage | TCZ IV Q4W |
|---|---|
| STARTED | 22 |
| COMPLETED | 22 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The pharmacokinetic (PK) population consisted of participants who received one dose of TCZ and had one valid PK sample, with participants grouped according to treatment received.
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 | TCZ IV Q4W |
|---|---|---|
| Participants analysed | 24 | |
| Age, Continuous | Years | 67.9 (SD 8.1) |
| Sex: Female, Male: Female | Participants | 15 |
| Sex: Female, Male: Male | Participants | 9 |
| Ethnicity (NIH/OMB): Hispanic or Latino | Participants | 0 |
| Ethnicity (NIH/OMB): Not Hispanic or Latino | Participants | 24 |
| Ethnicity (NIH/OMB): Unknown or Not Reported | Participants | 0 |
| Race (NIH/OMB): American Indian or Alaska Native | Participants | 0 |
| Race (NIH/OMB): Asian | Participants | 1 |
| Race (NIH/OMB): Native Hawaiian or Other Pacific Islander | Participants | 0 |
| Race (NIH/OMB): Black or African American | Participants | 0 |
| Race (NIH/OMB): White | Participants | 23 |
| Race (NIH/OMB): More than one race | Participants | 0 |
| Race (NIH/OMB): Unknown or Not Reported | Participants | 0 |
6. Primary Endpoint
The registry lists the primary outcome as Maximum Serum Concentration (Cmax) of TCZ, measured over Baseline; Weeks 4, 8, 12, 16-24.
| Element | Registry entry |
|---|---|
| Result type | Median |
| Measure of spread | Full Range |
| Unit | ug/mL |
| Endpoint classification | not reduced to a single comparison |
Maximum serum concentration, or Cmax, is the highest measured concentration of a drug in serum within a specified observation period. It is a pharmacokinetic measure: it describes drug exposure in the body, rather than directly measuring a clinical benefit. The registry gives the unit as ug/mL and specifies a median with the full range, assessed at baseline and Weeks 4, 8, 12, and 16-24.
General: Concentration measurements can help characterize how much drug is present in the bloodstream at particular points in a dosing schedule. Reporting a median gives a central summary that is less influenced by unusually high or low values than a mean can be. A full range describes the observed minimum and maximum, but does not show how values are distributed between those extremes. Concentration patterns can also be considered alongside pharmacodynamic measures, which describe biological responses, and safety observations. These are distinct types of evidence and should not be treated as interchangeable.
The registry defines the pharmacokinetic population as participants who received one dose of TCZ and had one valid pharmacokinetic sample, grouped according to treatment received. The size of that population and the numerical Cmax values are not reported in the registry record. Consequently, the listed endpoint definition and assessment schedule identify what was intended to be measured, but do not establish the observed concentration levels, their spread, or how they changed across assessments.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record describes a single-group, open-label, Phase Ib study focused on the pharmacokinetics, pharmacodynamics, and safety of TCZ in GCA. It reports 24 enrolled participants and a treatment sequence involving up to 6 doses of Dose 1 followed by up to 6 doses of Dose 2, both administered intravenously every 4 weeks. The listed dose-level groups are TCZ IV 7 mg/kg Q4W and TCZ IV 6 mg/kg Q4W. These design features give context for reading the record, but do not create a randomized comparison between dose levels.
The primary endpoint is maximum serum TCZ concentration, summarized as a median with full range at baseline and Weeks 4, 8, 12, and 16-24. The numerical endpoint results are not reported in the registry record. Without those values, the record does not support a description of the observed concentration levels, differences across assessment times, or variability among participants. The stated endpoint and schedule alone are not evidence of a particular pharmacokinetic pattern.
The registry lists pharmacodynamic outcomes involving IL-6, sIL-6R, CRP, and ESR. These outcomes can describe biological measurements, but their numerical findings are not reported in the registry record. Nor are numerical findings for the other listed outcomes available in the registry record. The registry reports zero analyses. The specific statistical procedures used for the outcomes, including any adjustments or model-based analyses, are not reported in the registry record.
Safety information includes serious adverse event counts for the two dose-level groups: 3 among 24 at risk in the 7 mg/kg Q4W group, and 1 among 22 at risk in the 6 mg/kg Q4W group. The registry also lists 6 other adverse events among 24 at risk in the 7 mg/kg group and 3 among 22 at risk in the 6 mg/kg group; deaths are listed as 0 in each group. These are descriptive counts, not evidence of a causal difference between dose levels. The study was not randomized, and the arm description indicates sequential exposure.
The record lists serious adverse event terms with percentages, but does not identify their group attribution in the summarized information. Those terms should be read as posted safety observations, not as a comparative analysis. Overall, the record supports a description of the study’s design, endpoint definitions, and selected safety counts. It does not provide the numerical primary pharmacokinetic results or enough analysis detail to draw conclusions about comparative dose effects or clinical outcomes.
9. Statistical Methods Explained
General: A clinical study’s design determines which comparisons its data can support. Random assignment can help make groups comparable at baseline, on average, by distributing measured and unmeasured participant characteristics across treatment groups. This registry lists allocation as not applicable, masking as none, and the model as single group. The arm description says participants could receive up to 6 doses of Dose 1 followed by up to 6 doses of Dose 2. Therefore, the two dose-level safety entries should not be treated as a randomized head-to-head comparison. Differences between their counts could reflect many features of who was observed, when they were observed, or how exposure was assigned; the record does not provide enough detail to separate those possibilities.
What does the primary measure summarize?
General: Cmax is a pharmacokinetic summary of the maximum measured serum drug concentration within an observation period. The registry specifies the median and full range at baseline and Weeks 4, 8, 12, 16-24. A median describes the middle of an ordered set of observations. A full range reports the lowest and highest observations, but gives no direct account of the distribution between them. It can also be sensitive to extreme observations. The concentration unit is ug/mL. Numerical Cmax results are not reported in the registry record, so no interpretation of observed concentrations or their spread is possible from the recorded details.
What is a pharmacokinetic population?
The registry defines this population as participants who received one dose of TCZ and had one valid pharmacokinetic sample, grouped according to treatment received. General: Such a definition specifies which participants can contribute to a pharmacokinetic summary; it need not be identical to the number enrolled or to the populations used for other outcomes. Participants can be excluded from an analysis if they do not meet the stated measurement criteria, but the number meeting the definition is not reported in the registry record. The record also does not describe the handling of values that were invalid, unavailable, or collected outside the stated assessment times.
What can the safety counts tell readers?
The serious adverse event entries give counts and the corresponding numbers at risk for each listed dose-level group. The other adverse event entries and deaths are also presented as counts. General: Counts describe how many participants had an event under the registry’s reporting definitions; they do not, by themselves, establish that the treatment caused an event. A comparison of event counts also needs careful consideration of the time participants were observed, how events were defined and collected, and whether the groups represent comparable participants. Those details are not reported in the registry record. The dose sequence and nonrandomized design make causal comparisons especially inappropriate on the basis of these counts alone.
How should planning illustrations be understood?
General: Sample-size calculations can illustrate how many participants per arm might be needed for a specified statistical design and target effect. The registry’s stated planning assumptions describe an illustration based on the observed effect, with a two-sided significance level of 0.05, equal allocation, and a normal approximation. They also state that the target is a chosen fraction of the observed effect. Such illustrations are not the trial’s own design justification and are not observed power. The registry does not report the trial’s sample-size justification. In addition, the study is single group and its dose sequence is not a randomized arm comparison, so equal-allocation planning assumptions should not be mistaken for the actual design.
The registry reports zero analyses. The statistical analysis procedures, including any covariate adjustment, missing-data method, interim analysis, or multiplicity strategy, are not reported in the registry record. General: An analysis method should be interpreted in light of its assumptions, the outcome scale, the amount and pattern of missing data, and the study design. Without a reported analysis plan and numerical endpoint results, readers cannot assess model fit, uncertainty around the primary estimate, or the robustness of any inferential conclusion.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists the primary endpoint as maximum serum TCZ concentration and names several pharmacodynamic secondary outcomes: serum concentrations of IL-6, sIL-6R, and CRP, plus ESR. It does not report a multiplicity strategy. General: When a study examines multiple outcomes or multiple assessment times, the chance of at least one apparently unusual finding can increase if each is tested separately. A prespecified strategy can clarify which findings are primary and how secondary results should be interpreted. The registry record does not state whether such adjustments or a hierarchy of tests were planned or applied.
The registry defines the pharmacokinetic population as participants who received one dose of TCZ and had one valid pharmacokinetic sample, grouped according to treatment received. The number meeting this definition is not reported in the registry record. The record also does not describe the analysis populations for pharmacodynamic outcomes or safety, or explain how incomplete measurements were handled. General: Missing observations can affect both the amount of information available and the interpretation of a result, particularly if participants with missing measurements differ systematically from those with observed measurements.
The registry reports zero analyses, and numerical primary endpoint results are not reported in the registry record. The specific statistical plan, missing-data methods, interim analyses, and handling of multiple outcomes are not reported in the registry record. These omissions limit assessment of how the planned analyses were carried out and how much uncertainty should attach to any outcome estimates.
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 |
|---|---|---|---|
| TCZ IV 7 mg/kg Q4W | 3 | 24 | 12.5% |
| TCZ IV 6 mg/kg Q4W | 1 | 22 | 4.5% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| TCZ IV 7 mg/kg Q4W | 0 of 24 |
| TCZ IV 6 mg/kg Q4W | 0 of 22 |
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 |
|---|---|
| TCZ IV 7 mg/kg Q4W | 6 of 24 |
| TCZ IV 6 mg/kg Q4W | 3 of 22 |
Most frequent serious adverse event terms
| Event term | Organ system | TCZ IV 7 mg/kg Q4W | TCZ IV 6 mg/kg Q4W |
|---|---|---|---|
| Vertigo positional | Ear and labyrinth disorders | 0 of 24 | 1 of 22 |
| Lower gastrointestinal haemorrhage | Gastrointestinal disorders | 1 of 24 | 0 of 22 |
| Pneumonia pneumococcal | Infections and infestations | 1 of 24 | 0 of 22 |
| Aortic aneurysm rupture | Vascular disorders | 1 of 24 | 0 of 22 |
Most frequent non-serious adverse event terms
| Event term | Organ system | TCZ IV 7 mg/kg Q4W | TCZ IV 6 mg/kg Q4W |
|---|---|---|---|
| Nasopharyngitis | Infections and infestations | 3 of 24 | 1 of 22 |
| Respiratory tract infection viral | Infections and infestations | 1 of 24 | 2 of 22 |
| Upper respiratory tract infection | Infections and infestations | 2 of 24 | 0 of 22 |
Serious events with the highest arm-level rate: vertigo positional (4.5%), lower gastrointestinal haemorrhage (4.2%), pneumonia pneumococcal (4.2%), aortic aneurysm rupture (4.2%).
The registry lists serious adverse event counts for TCZ IV 7 mg/kg Q4W as 3 participants with an event among 24 at risk, and for TCZ IV 6 mg/kg Q4W as 1 among 22 at risk. Other adverse event counts are listed as 6 among 24 at risk and 3 among 22 at risk, respectively. Deaths are listed as 0 in both groups. These are descriptive registry counts; they do not establish that TCZ caused or prevented an event.
The registry also lists serious adverse event terms with percentages: Vertigo positional, 4.5%; Lower gastrointestinal haemorrhage, 4.2%; Pneumonia pneumococcal, 4.2%; and Aortic aneurysm rupture, 4.2%. The summarized record does not attribute these terms to a particular dose-level group, so they should not be assigned to one. The denominator and event-level details for these term percentages are not reported in the registry record.
General: Safety counts are most useful when read with definitions, observation time, and participant exposure. The registry identifies numbers at risk but does not report the details needed to compare exposure duration or event ascertainment across groups. Since treatment was not randomized and the description involves sequential dose exposure, these figures do not support a causal comparison of dose levels.
12. What the Result Does, and Does Not, Mean
The record establishes that a completed Phase Ib, open-label, dose-ranging study evaluated intravenous TCZ in participants with GCA. It records 24 enrolled participants, a dosing schedule every 4 weeks, and an intended sequence of up to 6 doses of Dose 1 followed by up to 6 doses of Dose 2. It also defines a pharmacokinetic primary endpoint and lists pharmacodynamic measures and safety outcomes.
Those details describe the study’s aims and design, but they do not show the numerical primary endpoint findings. Cmax is specified as a median with full range, assessed at baseline and Weeks 4, 8, 12, and 16-24; the actual values are not reported in the registry record. Numerical findings for the listed pharmacodynamic outcomes are also not reported in the registry record. As a result, the registry entries do not establish the observed serum concentration profile or the size and variability of any biological changes.
The adverse event counts provide selected descriptive safety information. They are not a randomized comparison, and the listed dose-level groups should not be treated as equivalent groups assigned independently to different treatments. The record does not give the details required to determine whether differences in counts reflect treatment, duration of exposure, participant characteristics, or other factors. Nor do the counts alone establish causation.
General: A study’s endpoint definitions and design can clarify what its investigators set out to measure, while numerical estimates and their uncertainty are needed to characterize what was observed. A single-group, open-label study can provide descriptive information, but it cannot by itself establish a randomized comparative treatment effect. The sample-size assumptions described in the record are planning illustrations, not evidence of achieved power or a justification for the completed study. The registry does not report the study’s own sample-size rationale or a statistical analysis plan.
Accordingly, the record supports a careful account of design, measurement, and selected safety counts. It does not support conclusions about the magnitude or precision of the primary pharmacokinetic result, comparative dose effects, or clinical benefit.
13. Why This Trial Matters Statistically
This study is statistically notable for the distinction between a pharmacokinetic question and a comparative clinical question. Its primary endpoint, maximum serum TCZ concentration, concerns drug exposure. The registry specifies a median and full range at several assessment times, but does not report the numerical values. This means the endpoint’s definition and schedule are known, while its observed level and variability cannot be evaluated from the registry record.
The design also matters. The study is listed as single group, open-label, and without applicable allocation, and the treatment description gives a sequence of Dose 1 followed by Dose 2. Although safety information is organized by dose level, that arrangement is not a randomized control comparison. Statistical contrasts between such groups would require assumptions and design details that are not reported in the registry record. The counts should therefore remain descriptive.
The record lists both pharmacokinetic and pharmacodynamic outcomes, along with safety observations. Keeping these evidence types distinct is important: concentration measurements describe drug exposure, while IL-6, sIL-6R, CRP, and ESR are listed as biological outcomes. Neither category alone is equivalent to a clinical outcome. The registry entries do not report numerical findings for the primary endpoint or listed secondary outcomes.
Finally, the record’s planning assumptions should not be confused with evidence that the study was powered for a particular comparison. The assumptions describe an illustration, while the study’s own sample-size rationale is not reported. These features make the registry a useful account of what was measured and how the treatment sequence was described, but not a basis for estimating comparative efficacy or making causal conclusions from the posted counts.
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 primary limitation for interpretation is that numerical Cmax results are not reported in the registry record. Although the endpoint, summary measure, unit, and assessment times are specified, readers cannot assess the concentration values, their full range, or how they vary over the recorded assessments. Numerical findings for the listed pharmacodynamic outcomes are also not reported in the registry record.
The study is described as single group, open-label, and not randomized. Its treatment description specifies sequential doses, while the safety information is organized under two dose-level group titles. The record does not explain the participant flow between those entries or give enough detail to treat them as independent groups. Consequently, the safety counts are not a like-for-like comparative estimate.
The registry does not report the number of participants in the defined pharmacokinetic population, the analysis populations for other outcomes, or how missing or invalid measurements were handled. The statistical analysis plan, multiplicity approach, interim analyses, and sample-size justification are also not reported in the registry record. The record lists zero analyses, so the procedures used to produce outcome estimates are not described in the registry record.
For safety interpretation, the record gives counts and numbers at risk, but the observation duration and detailed event ascertainment are not reported in the registry record. It also lists serious adverse event terms and percentages without group attribution in the summarized information. These limits prevent causal interpretation or a reliable comparison of event frequency by dose level.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Evaluate the Pharmacokinetics, Pharmacodynamics, and Safety of Tocilizumab (TCZ) Administered to Participants With Giant Cell Arteritis (GCA). — NCT03923738.
- Registry record last updated 2021-12-22; status last verified 2021-11.
- Results first posted 2021-12-22.
- 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
The registry describes NCT03923738 as a completed Phase Ib, open-label, dose-ranging study of intravenous TCZ in participants with GCA. It lists 24 enrolled participants and an every-4-weeks dosing schedule, with up to 6 doses of Dose 1 followed by up to 6 doses of Dose 2.
The primary endpoint was maximum serum TCZ concentration, summarized as a median with full range at baseline and Weeks 4, 8, 12, 16-24. The pharmacokinetic population required one dose and one valid pharmacokinetic sample. Numerical primary results are not reported in the registry record. Secondary outcomes listed include IL-6, sIL-6R, CRP, and ESR.
Safety counts are reported for TCZ IV 7 mg/kg Q4W and TCZ IV 6 mg/kg Q4W, but the design is not randomized and should not be read as a like-for-like control comparison. The registry does not report the statistical analysis plan, missing-data approach, multiplicity strategy, or the study’s sample-size justification.