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 Assess the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis (NCT04740814), a na phase 1 study. The primary outcome is Minimum Observed Plasma Concentration (Cmin) Post 10 Weeks of Certolizumab Pegol Dosing.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT04740814 |
| Phase | Phase 1 |
| Condition | Rheumatoid Arthritis |
| Allocation | Not applicable (single group) |
| Design model | Single Group |
| Masking | None (open label) |
| Enrollment | 33 |
| Arms in the primary outcome | n/a |
| Lead sponsor | UCB Biopharma SRL |
| Results posted | Yes |
2. Clinical Question
Population
Adults with active rheumatoid arthritis were the intended study population. The registry describes a Pharmacokinetic Set (PKS) consisting of participants with measurable plasma concentrations and recorded sampling time on at least one visit, without important protocol deviations affecting pharmacokinetic parameters. The registry does not report the number included in that analysis set.
Intervention
Participants received certolizumab pegol. The arm description says dosing followed the US label; the registry does not give the dosing schedule or dose amounts in the information recorded for this endpoint.
Comparator
There was no separate comparator arm. This was an open-label, single-group study, and the allocation field is recorded as NA. Its results therefore do not provide a randomized, like-for-like comparison with another treatment or a control group.
Primary question
The primary endpoint concerns the minimum observed plasma concentration of certolizumab pegol after 10 weeks of dosing. It asks what the observed trough concentration was during the dosing interval, as summarized by a geometric mean and geometric coefficient of variation. The registry record does not report the resulting estimate.
The study’s stated purpose was to evaluate pharmacokinetics and safety in adults with active rheumatoid arthritis. Its primary endpoint is a drug-concentration measure, not a measure of rheumatoid arthritis symptoms, function, or clinical response. The listed secondary outcomes include plasma concentrations during the study and adverse-event measures. The posted record describes a study of drug exposure and safety, rather than a controlled test of comparative clinical benefit.
3. Trial Design
This was a Phase 1, multicenter, open-label study of certolizumab pegol in adults with active rheumatoid arthritis. The registry records a single-group model, no masking, and allocation as NA. The intervention arm is certolizumab pegol, with dosing described as being in accordance with the US label. No separate control or comparator arm is described, so the study is not a randomized comparison.
Enrollment is recorded as 33. The study started on 2021-02-11, reached primary completion on 2022-01-24, and has a completed status. The sponsor is UCB Biopharma SRL. These administrative details describe the record but do not establish how many participants contributed data to each endpoint or analysis.
The primary outcome is minimum observed plasma concentration, or Cmin, after 10 weeks of dosing. Plasma sampling was scheduled at Pre dose on Day 70 (Week 10), 72, 75, 77 and 80 post-Week 10 study Investigational Medicinal Product administration, and Pre dose on Day 84 (Week 12). The endpoint’s stated summary measure is the geometric mean, with geometric coefficient of variation as its dispersion measure.
The registry lists five outcome measures and 0 analyses. It identifies plasma concentration during the study and adverse-event outcomes among the secondary measures. The record does not report the primary endpoint estimate, its dispersion result, confidence intervals, or inferential test results. It also does not report a sample-size justification, a detailed statistical analysis plan, interim analyses, or detailed dosing amounts. The study’s design can therefore be characterized from its registration fields, but the listed information does not support a conclusion about the magnitude or precision of the observed pharmacokinetic result.
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: The Participant Flow refers to the Safety Set.
Overall Study
| Stage | Certolizumab Pegol (All Participants) |
|---|---|
| STARTED | 33 |
| COMPLETED | 23 |
| NOT COMPLETED | 10 |
Reasons for not completing this period:
| Reason | Certolizumab Pegol (All Participants) |
|---|---|
| Adverse Event | 3 |
| Protocol Violation | 2 |
| Lost to Follow-up | 2 |
| Withdrawal by Subject | 3 |
Analysis population for the primary outcome, as defined in the registry: The Pharmacokinetic Set (PKS) included the study participants who had provided plasma samples with measurable concentrations (with recorded sampling time) on at least 1 visit, and who had no important protocol deviations affecting the PK parameters. Here, Number of participants analyzed included those participants who were evaluable for the assessment.
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: Baseline Characteristics refer to the Safety Set (SS) which consisted of all study participants enrolled who received greater than or equal to (≥) 1 injection of study medication.
| Characteristic | Unit | Certolizumab Pegol (All Participants) |
|---|---|---|
| Participants analysed | 33 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 27 |
| Age, Categorical: >=65 years | Participants | 6 |
| Age, Continuous | years | 55.9 (SD 10.6) |
| Sex: Female, Male: Female | Participants | 22 |
| Sex: Female, Male: Male | Participants | 11 |
| Race/Ethnicity, Customized: Black | Participants | 7 |
| Race/Ethnicity, Customized: White | Participants | 25 |
| Race/Ethnicity, Customized: Missing | Participants | 1 |
| Race/Ethnicity, Customized: Hispanic or Latino | Participants | 9 |
| Race/Ethnicity, Customized: Not Hispanic or Latino | Participants | 24 |
6. Primary Endpoint
The registry lists the primary outcome as Minimum Observed Plasma Concentration (Cmin) Post 10 Weeks of Certolizumab Pegol Dosing, measured over Plasma samples were collected at Pre dose on Day 70 (Week 10), 72, 75, 77 and 80 post-Week 10 study Investigational Medicinal Product (IMP) administration, and Pre dose on Day 84 (Week 12).
| Element | Registry entry |
|---|---|
| Result type | Geometric Mean |
| Measure of spread | Geometric Coefficient of Variation |
| Unit | micrograms per milliliter (ug/mL) |
| Endpoint classification | not reduced to a single comparison |
Cmin is defined in the registry as the minimum observed plasma drug concentration during a dosage interval. The primary endpoint is the minimum observed concentration of certolizumab pegol after 10 weeks of dosing, measured in micrograms per milliliter (ug/mL). It is summarized using a geometric mean and geometric coefficient of variation.
A trough concentration is useful in pharmacokinetic description because it reflects the lower observed drug concentration around a dosing interval, rather than a peak concentration after administration. Repeated plasma sampling across the specified visits can characterize concentrations around the period following Week 10 dosing. This is a general explanation of the role of a trough measure; the registry does not give a concentration estimate or describe how the observed samples were combined into the endpoint.
The geometric mean is a way to summarize positive measurements that may vary multiplicatively. The geometric coefficient of variation describes relative variability on a geometric scale. These summaries can be useful when concentration measurements are skewed rather than symmetrically distributed on their original scale. This is a general statistical rationale, not evidence about the distribution of the measurements in this study.
The endpoint is a pharmacokinetic measure, not a direct measure of treatment response or safety. No numerical Cmin result, geometric coefficient of variation, confidence interval, or analysis population count is reported in the registry record. The endpoint’s stated definition and sampling schedule are available, but its observed value and precision cannot be assessed from the record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registered primary question is descriptive: what minimum observed plasma concentration of certolizumab pegol was measured after 10 weeks of dosing? The endpoint is defined, and its unit and summary approach are stated. However, no endpoint result is reported in the registry record. There is consequently no posted geometric mean or geometric coefficient of variation from which to describe the observed concentration or its variability.
The record also lists 0 analyses. It does not report a confidence interval, standard error, hypothesis test, or other inferential result for the primary endpoint. The absence of these results means that the precision of the estimate cannot be evaluated. A confidence interval, as a general statistical concept, expresses uncertainty around an estimate under the assumptions of the analysis; without an interval or the underlying estimate, no interval-based interpretation is possible.
The study’s single-group, open-label design is important for interpreting its scope. It can describe drug concentrations observed among participants meeting the pharmacokinetic analysis-set definition, but it does not create a concurrent control comparison. Any observed concentration would characterize the participants and sampling conditions studied; it would not, by itself, establish a difference from another drug, dose, or treatment strategy. The registry’s dosing description refers to the US label but does not provide the detailed regimen.
Enrollment is recorded as 33, but that number should not be treated as the number analyzed for every outcome. The PKS definition requires measurable concentrations with recorded sampling time on at least one visit and no important protocol deviations affecting pharmacokinetic parameters. The number meeting that definition is not reported in the registry record. Nor does the registry provide endpoint-specific missingness or explain whether observations from all scheduled visits contributed to the primary summary.
Safety results should be interpreted separately from the pharmacokinetic endpoint. The registry lists serious adverse events, other adverse events, and adverse events leading to withdrawal as secondary outcomes. Its adverse-event fields report 2 serious adverse events among 33 at risk, 9 other adverse events among 33 at risk, and 1 death. These are descriptive counts in a single-group study; the record does not establish causation or provide a control group for comparison. The listed serious-event terms include Cardiac arrest and Cerebrovascular accident, each with 3.0% recorded.
Overall, the registry gives enough information to identify the study’s population, intervention, design, primary measure, and sampling schedule. It does not give the primary numerical result or inferential analyses. The evidence available in the record therefore supports a description of the intended pharmacokinetic assessment and reported safety counts, but not a quantitative assessment of the primary endpoint’s size or precision.
9. Statistical Methods Explained
The registry describes a single-group study with an open-label design. In general, an open-label study does not mask the assigned intervention from participants or investigators. A single-group design describes outcomes within the treated group; unlike a controlled comparison, it does not estimate a between-group treatment contrast. Those design features frame what can be inferred from any reported result. They do not supply a missing result, and the primary endpoint estimate is not reported in the registry record.
Why use a geometric mean?
Pharmacokinetic concentrations are often positive and can vary multiplicatively. In general, the geometric mean summarizes measurements after taking logarithms, averaging on that scale, and transforming back. It is therefore distinct from an arithmetic average. The geometric coefficient of variation is a relative dispersion summary associated with the geometric scale. These measures may be informative when values are right-skewed or when proportional differences are more meaningful than absolute differences. The registry names these summaries, but does not report their values or the distribution of observed concentrations.
What does Cmin represent?
The registry defines Cmin as the minimum observed plasma drug concentration during a dosage interval. A trough measure is intended to describe the low point in concentration over that interval. The planned collection times include Pre dose on Day 70 (Week 10), 72, 75, 77 and 80 post-Week 10 study Investigational Medicinal Product administration, and Pre dose on Day 84 (Week 12). The record does not explain whether the primary Cmin was selected from all these samples, how samples from different visits were handled, or whether a particular visit was required for inclusion in the endpoint analysis.
Why does the analysis population matter?
The PKS definition includes study participants with measurable concentrations and recorded sampling time on at least one visit, provided there were no important protocol deviations affecting the pharmacokinetic parameters. This is an endpoint-specific eligibility definition, rather than a statement that every enrolled participant contributed to the primary result. The number analyzed in the PKS is not reported in the registry record. In general, the analysis population affects how broadly a result can be interpreted and whether missing or unmeasurable samples might influence the estimate.
What would precision measures add?
A point estimate would describe the center of the observed concentration measurements according to the chosen summary. A confidence interval would convey uncertainty around that estimate under the analysis assumptions. A dispersion measure such as the geometric coefficient of variation describes variability among observations; it does not serve the same purpose as a confidence interval for the mean. No point estimate, confidence interval, or dispersion value is reported for this endpoint, so its numerical precision and observed variability cannot be assessed.
Why are control comparisons unavailable?
With a single group and no separate comparator, the analysis is not a randomized treatment comparison. A descriptive pharmacokinetic result could characterize concentration measurements in this study, but there is no concurrent control estimate against which to quantify a difference. General explanations of comparative inference cannot replace a comparison absent from the design. The record does not specify an external comparator or a statistical method for comparing this group with another population.
How should the safety counts be read?
Safety counts describe events recorded in the study group. They are not, by themselves, estimates of excess risk attributable to treatment. A control group can help contextualize event frequencies, while an uncontrolled study cannot make the same direct comparison. The registry reports event counts and some event terms, but does not provide comparative analyses or establish whether events were judged related to treatment. The serious-event count, other-event count, and death count should therefore remain descriptive.
The registry records 0 analyses and does not include a detailed statistical plan. There is no basis in the record to describe a prespecified inferential model, a test, an adjustment strategy, or a variance-estimation procedure. General statistical concepts can explain how such methods might be used, but they cannot be attributed to this study without documentation. Likewise, no sample-size justification or interim-analysis plan is reported. The enrollment figure alone does not show whether the study was designed to achieve a particular level of precision.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists five outcome measures and 0 analyses. It identifies the primary pharmacokinetic outcome and lists secondary outcomes that include plasma concentrations during the study, treatment-emergent serious adverse events, and treatment-emergent adverse events leading to withdrawal. The registry record does not report a multiplicity strategy, such as an adjustment for testing multiple outcomes, or describe a hierarchy of confirmatory tests. Since inferential analyses are not listed, there are no reported p-values to interpret across outcomes.
The primary endpoint’s stated analysis population is the PKS: participants with measurable concentrations and recorded sampling time on at least one visit, with no important protocol deviations affecting pharmacokinetic parameters. The number analyzed is not reported. The record does not provide a participant flow for the endpoint, the amount or pattern of missing concentration data, or a missing-data method. The scheduled plasma sampling times are described, but that schedule does not establish that every sample was collected or included.
In general, missing pharmacokinetic measurements can affect both the number of observations available and the representativeness of the analyzed measurements. The impact depends on why measurements are missing and on the analysis approach. Those details are not reported in the registry record, so the direction or magnitude of any potential impact cannot be assessed. The record also does not state whether sensitivity analyses were planned or performed.
The safety outcomes have reported counts, but the record does not provide corresponding inferential comparisons or a multiplicity plan for those outcomes. Their interpretation should remain descriptive rather than implying a prespecified statistical test or adjusted conclusion.
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 |
|---|---|---|---|
| Certolizumab Pegol (All Participants) | 2 | 33 | 6.1% |
Deaths
| Arm | Deaths (participants affected of at risk) |
|---|---|
| Certolizumab Pegol (All Participants) | 1 of 33 |
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 |
|---|---|
| Certolizumab Pegol (All Participants) | 9 of 33 |
Most frequent serious adverse event terms
| Event term | Organ system | Certolizumab Pegol (All Participants) |
|---|---|---|
| Cardiac arrest | Cardiac disorders | 1 of 33 |
| Cerebrovascular accident | Nervous system disorders | 1 of 33 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Certolizumab Pegol (All Participants) |
|---|---|---|
| Upper respiratory tract infection | Infections and infestations | 3 of 33 |
| Nausea | Gastrointestinal disorders | 2 of 33 |
| Rheumatoid arthritis | Musculoskeletal and connective tissue disorders | 2 of 33 |
| Urinary tract infection | Infections and infestations | 2 of 33 |
Serious events with the highest arm-level rate: cardiac arrest (3.0%), cerebrovascular accident (3.0%).
The registry reports 2 serious adverse events among 33 at risk in the Certolizumab Pegol (All Participants) group. It also reports 9 other adverse events among 33 at risk and 1 death. These are separate recorded safety figures; the registry does not state that the death was caused by treatment or provide a comparative group for interpreting the counts.
The listed serious-event terms are Cardiac arrest and Cerebrovascular accident, each recorded as 3.0%. These entries identify reported event terms and percentages, but the registry does not provide additional context about event timing, severity beyond the serious-event classification, relatedness assessment, or whether a participant had more than one event. The record also lists treatment-emergent adverse events leading to withdrawal as a secondary outcome, but does not report a result for that outcome in the registry record.
In general, adverse-event counts in a single-group study describe what was recorded among participants under observation. They do not estimate a treatment-attributable difference, because no concurrent control group is described. The at-risk counts are the relevant denominators recorded for these safety fields; they should not be assumed to be the analysis denominator for the pharmacokinetic endpoint.
12. What the Result Does, and Does Not, Mean
The registry record establishes that the study assessed pharmacokinetics and safety of certolizumab pegol in adults with active rheumatoid arthritis. It identifies a primary endpoint based on minimum observed plasma concentration after 10 weeks of dosing, specifies a geometric mean and geometric coefficient of variation, and gives the planned sampling schedule. It also records safety counts for the study group.
It does not report the primary endpoint estimate or its variability. No confidence interval or inferential analysis is listed, and the registry records 0 analyses. As a result, the observed concentration level and the precision of its estimate cannot be determined from the registry record. A defined outcome and sampling plan explain what was intended to be measured; they do not establish what the measurements showed.
The study design also limits the kind of conclusion that could be drawn from a reported result. Because it is single-group and open-label, it does not provide a randomized comparison with another treatment or a control group. Any pharmacokinetic summary would describe measurements in the analyzed participants, not a comparative treatment effect. The record does not provide an analysis population count, and its PKS definition means that enrollment cannot automatically be equated with the number contributing to the primary result.
The safety figures are descriptive. They do not establish that treatment caused the listed events, nor do they show how event frequencies compare with another group. The registry does not report a causal assessment or comparative safety analysis. Overall, the record documents the study’s question, design, endpoint definition, and selected safety counts, while leaving the primary quantitative result and its statistical precision unreported.
13. Why This Trial Matters Statistically
This study is statistically notable for the distinction between measuring drug exposure and evaluating clinical outcomes. Its primary endpoint is a plasma concentration measure, Cmin, rather than a clinical response measure. The geometric mean and geometric coefficient of variation reflect a pharmacokinetic summary approach. Understanding that endpoint prevents a concentration result, if reported, from being mistaken for a direct measure of symptom change or comparative clinical benefit.
The study also illustrates how design determines the scope of inference. A single-group, open-label study can document observations under the studied dosing conditions, but it does not provide a randomized control comparison. Its results would therefore be descriptive of the study group and would not directly estimate a contrast against an alternative treatment. That distinction remains important even when a study has a clearly stated outcome and sampling schedule.
Analysis-population definitions are another key statistical feature. The PKS requires measurable concentrations, recorded sampling time on at least one visit, and no important protocol deviations affecting pharmacokinetic parameters. Because the number meeting that definition is not reported, enrollment alone cannot establish how many contributed to the primary summary. Endpoint-specific participation and missing measurements matter when interpreting both the estimate and its precision.
Finally, the registry record demonstrates the difference between a registered question and a reported result. The primary endpoint is described, but its numerical estimate and statistical analyses are not reported. The study’s safety counts can be read descriptively, while causal and comparative conclusions are outside what these single-group figures establish. These features make careful attention to endpoint definition, analysis population, and reporting completeness central to interpretation.
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 statistical interpretation is that the registry record does not report the primary Cmin result. Although the endpoint’s unit, summary measure, dispersion measure, and sampling schedule are recorded, the geometric mean and geometric coefficient of variation are absent. The record also lists 0 analyses, leaving no reported confidence interval, hypothesis test, or model-based result with which to assess statistical precision.
The single-group, open-label design has no separate comparator arm. It cannot support a randomized comparison of pharmacokinetic values or safety outcomes against another treatment group. The registry does not describe an external comparison or an adjustment method that might support a separate comparative analysis.
The number in the PKS is not reported. The registry defines that population by measurable concentrations, sampling-time records, and absence of important protocol deviations affecting pharmacokinetic parameters. It does not report how many participants met these criteria, how many measurements were missing, or how missing samples were handled. The enrollment figure should not be treated as the endpoint analysis count.
The record does not report a detailed dosing regimen, sample-size justification, statistical analysis plan, interim analyses, multiplicity strategy, or sensitivity analyses. These omissions limit assessment of how the endpoint was intended to be analyzed and how robust any result might be. The safety information is also limited to recorded counts and selected terms, without a control group or reported causal attribution. These limitations concern what is available in the registry record and do not establish whether additional information exists elsewhere.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: A Study to Assess the Pharmacokinetics of Certolizumab Pegol in Adults With Active Rheumatoid Arthritis — NCT04740814.
- Registry record last updated 2024-02-12; status last verified 2024-02.
- Results first posted 2023-11-13.
- 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
NCT04740814 is a completed Phase 1, multicenter, open-label, single-group study sponsored by UCB Biopharma SRL. It enrolled 33 adults with active rheumatoid arthritis and evaluated certolizumab pegol. The study started on 2021-02-11 and reached primary completion on 2022-01-24.
The primary outcome is minimum observed plasma concentration after 10 weeks of dosing, summarized by geometric mean and geometric coefficient of variation. The registry specifies sampling times from Pre dose on Day 70 (Week 10) through Pre dose on Day 84 (Week 12), but does not report the primary result. It lists five outcome measures and 0 analyses.
Safety fields record 2 serious adverse events among 33 at risk, 9 other adverse events among 33 at risk, and 1 death. Cardiac arrest and Cerebrovascular accident are each listed at 3.0%. The record describes no comparator group, and these safety figures are descriptive.