Comparative Evaluation of Pharmacokinetics and Safety of BCD-055 and Remicade in Patients With Ankylosing Spondylitis: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Comparative Evaluation of Pharmacokinetics and Safety of BCD-055 and Remicade in Patients With Ankylosing Spondylitis (NCT02359903), a randomized phase 1 study. The primary outcome is Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 336 Hours After the Single Infusion of BCD-055/Remicade.

2. Clinical Question

The comparison is between two infliximab products rather than between infliximab and no treatment. The primary outcome concerns drug exposure over a stated period, not a direct measure of symptom improvement. The registry also names ASAS20 as a secondary outcome, but does not give a result for it in the record summarized by these primary results.

3. Trial Design

This was a randomized, double-blind, parallel-group phase 1 study sponsored by Biocad. The registry describes it as international and multicenter. It lists an enrollment of 90 and a completed status. The record gives a start of 2015-02 and primary completion of 2015-11.

Participants were assigned to BCD-055 or Remicade. Both groups were scheduled to receive infliximab at 5 mg/kg by slow intravenous infusion on weeks 0, 2, 6, 14 and 22. Because the products share the active drug named in the record, the main comparison is between product groups under the stated dosing schedule.

The primary endpoint was measured after a single infusion over a timeframe of 2 weeks. For this outcome, the registry describes a population of patients who received at least one injection. It states that one patient in the BCD-055 group was excluded because blood collection did not follow the required timing, and that two patients in the Remicade group were excluded because of an adverse event or serious adverse event. The record gives primary-outcome group sizes of 44 and 43, respectively; these are the reported analysis sizes and should not be interpreted as a reconciliation of all enrolled or treated participants.

The available record does not report details of the randomization method, allocation concealment, masking procedures, or the statistical analysis plan. It also does not report the planned sample-size justification. These omissions limit assessment of how allocation and analysis were implemented, even though randomization, double masking and parallel assignment are recorded design features.

4. Participant Flow and Accounting

The registry reports how participants moved through each stage of the study. All counts below are exactly as posted; missing counts are not inferred from other stages.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Patients who received at least 1 injection. From BCD-055 group 1 patient was excluded because of violation of timing of blood collection. From Remicade group 2 patients were excluded due to AE/SAE.

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: All patients who received at least 1 injection of study drug

6. Primary Endpoint

The registry lists the primary outcome as Area Under the Plasma Concentration-time Curve From Zero (0) Hours to 336 Hours After the Single Infusion of BCD-055/Remicade, measured over 2 weeks.

The primary outcome is the area under the plasma concentration-time curve for infliximab from 0 hours to 336 hours after a single infusion. Its unit is (ng/ml)*hour, and the stated timeframe is 2 weeks. An area under a concentration-time curve represents drug exposure across the measurement period: it reflects concentrations over time rather than a concentration at only one sampling point.

As a general pharmacokinetic concept, comparing exposure can help assess whether two products produce similar drug levels over a defined period. That makes exposure a relevant endpoint for a study whose stated aim was pharmacokinetic equivalence. The registry reports the outcome as a median with an inter-quartile range. The BCD-055 group median is 26280000.0, with interval endpoints 21090000.0 and 32300000.0. The Remicade group median is 25910000.0, with interval endpoints 20110000.0 and 32660000.0.

These descriptive summaries alone do not establish equivalence. The registry record does not state a prespecified equivalence margin or report a confidence interval for the between-group contrast. The endpoint is also not itself a clinical benefit outcome: it describes measured drug exposure, not how patients felt or functioned.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry reports a median and inter-quartile range for the primary pharmacokinetic endpoint. These summaries describe the center and spread of the observed values without assuming that the distribution is symmetric. As a general statistical explanation, the median is the middle observation when values are ordered, and the inter-quartile range describes the span of the middle half of a distribution. These measures can be useful when data are skewed or include unusually high or low observations. The registry gives the interval endpoints rather than a single inter-quartile-range width.

The primary outcome is an area under the concentration-time curve, which combines concentration measurements across a defined time interval. In general, pharmacokinetic measurements taken over time can be summarized as exposure, peak concentration, trough or minimum concentration, and the time at which a peak occurs. The record lists these kinds of measures among its secondary outcomes, along with average concentration at steady state and half-life. Naming an outcome does not show its result: the registry record does not provide analysis results for those secondary measures in the available record.

Randomization is intended, in general, to make treatment groups comparable with respect to measured and unmeasured characteristics before treatment, while blinding is intended to reduce opportunities for expectations to influence care or assessment. The record labels this study randomized and double blind, with a parallel model. It does not report the sequence-generation or allocation-concealment methods, who was masked, or whether masking was maintained. Those implementation details are not reported in the registry record, so the labels alone cannot resolve those questions.

Equivalence testing has a different interpretation from a test designed only to detect a difference. As a general concept, an equivalence study needs a prespecified range of differences considered acceptably small. The analysis must then establish that the plausible values for the treatment contrast fall within that range. A nonsignificant difference test, if one were reported, would not by itself establish equivalence. In this record, the intended aim is described as pharmacokinetic equivalence, but no margin, contrast estimate, confidence interval or test result is reported. Thus, the summaries cannot be read as a completed equivalence analysis.

Confidence intervals, in general, express uncertainty around an estimated quantity under a specified statistical procedure. They are not the same as the range of individual observations or an inter-quartile range. The registry provides inter-quartile range endpoints for the group summaries but does not provide a confidence interval for the between-group comparison. Therefore, overlap between the reported intervals should not be treated as a formal test of equivalence or as a direct measure of the uncertainty in the treatment contrast.

The record also describes planning illustrations based on the observed effect. Their stated assumptions are a two-sided significance level of 0.05, equal allocation between the groups, a normal approximation, and detection of a stated fraction of the observed effect. Such illustrations are planning calculations, not observed power and not evidence that the original study was designed with those assumptions. The registry does not report a sample-size justification for the trial itself. No numerical planning estimate is stated in the available record, so no such estimate can be interpreted.

For adverse events, the record gives counts among participants at risk in each group. In general, event counts and participant counts answer different questions: counts describe how many events or affected participants were recorded, while the number at risk supplies the group context. The record does not provide event-level timing, duration, recurrence, or a detailed definition for each category. The listed figures should therefore be read as a limited safety summary rather than a complete account of the event experience.

The registry lists zero analyses. This absence matters because it leaves no reported inferential procedure for the primary comparison, no adjustment details for other outcomes, and no reported handling of missing observations beyond the exclusions described for the primary population. General statistical considerations cannot fill in those trial-specific methods; the actual analysis plan and its implementation are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

The record lists 23 outcome measures and names multiple secondary pharmacokinetic outcomes as well as ASAS20. It reports zero analyses in the available analysis information. A multiplicity strategy, such as a prespecified hierarchy or adjustment for testing several outcomes, is not reported in the registry record. Without that information and without reported secondary results, the secondary outcomes cannot be used to make an inferential claim or to confirm the primary finding.

The primary-outcome description says the analysis population consisted of patients who received at least one injection. It also records that one BCD-055 participant was excluded because of a blood-collection timing violation and two Remicade participants were excluded due to an adverse event or serious adverse event. The primary group sizes reported are 44 and 43. The record does not state whether these exclusions were the only missing primary measurements, how missing concentrations were handled, or whether sensitivity analyses were performed.

The registry does not report an intention-to-treat analysis, a per-protocol analysis, imputation methods, or other analysis-population definitions beyond the primary-outcome description. These details matter in an equivalence study because exclusions or missing measurements can influence the observed similarity between groups. The record does not provide enough information to assess the impact of those choices or to determine whether the analysis populations were selected before results were known.

11. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: collapse (2.2%).

The safety summary lists serious adverse events among 45 participants at risk in each group. It records zero affected participants in the BCD-055 group and one in the Remicade group. These are counts of participants affected, not a measure of the severity, duration or clinical course of every event. The record does not report deaths for either group.

The summary also lists other adverse events affecting four participants in each group, with 45 at risk in each group. The serious-event term shown is Collapse at 2.2%; the record does not assign that term to a treatment group in the available information. It should not be interpreted as an additional event on top of the group-level counts without clarification of the registry’s coding.

As a general statistical point, event counts in a trial describe what was recorded during the specified observation and reporting process. They do not by themselves establish that the treatments have equal safety, particularly when event counts are limited. The registry record does not give a detailed event listing, follow-up duration for safety, or definitions and relatedness assessments for the adverse-event categories. The figures support a narrow description of the reported counts, not a broad comparative safety conclusion.

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

The posted primary summaries describe infliximab exposure after a single infusion in the BCD-055 and Remicade groups. Their medians and inter-quartile range endpoints are of similar scale, and the reported intervals overlap. This is a descriptive comparison of the recorded pharmacokinetic values in the stated primary population.

It does not establish pharmacokinetic equivalence. The registry record does not report an equivalence margin, an estimated treatment contrast with a confidence interval, or an inferential analysis. Similar-looking medians and overlapping inter-quartile ranges cannot replace those elements. The stated study aim should be distinguished from what can be concluded from the results available in the record.

The outcome also does not directly establish a difference or similarity in symptoms, function, or other patient-centered outcomes. Although ASAS20 appears among the named secondary outcomes, a corresponding result is not reported in the available analysis information. Nor do the limited adverse-event counts establish that the products have equal safety. They describe recorded events among the participants at risk, with little additional detail in the record.

More generally, the trial’s phase 1 designation and its pharmacokinetic focus define the type of evidence being presented. The registry describes a randomized, double-blind comparison using the same stated dose and infusion schedule, but does not report enough statistical detail to assess the formal equivalence claim. The results should therefore be read as the reported descriptive exposure and safety summaries, not as a definitive conclusion about equivalence or clinical effects.

13. Why This Trial Matters Statistically

This trial is statistically notable because its stated purpose was to assess pharmacokinetic equivalence between two infliximab products. In that setting, the key question is not simply whether the group summaries look close. The analysis needs to connect the treatment contrast to a prespecified equivalence margin and quantify uncertainty around that contrast. Those elements are not reported in the registry record.

The endpoint is an exposure measure over a defined period after infusion, and the registry summarizes it with medians and inter-quartile ranges. That presentation makes the observed distributions visible, while leaving open the inferential question about how precisely the groups differ. This distinction is useful for readers assessing a clinical-trial record: descriptive summaries and a formal equivalence conclusion are not interchangeable.

The stated exclusions also illustrate why analysis populations matter. The reasons recorded differ between groups, including a timing issue for blood collection and adverse events or serious adverse events. The record does not report sensitivity analyses or further missing-data handling, so the effect of those exclusions cannot be assessed from the available results.

Finally, the record lists numerous secondary outcomes but no analyses. This emphasizes the importance of prespecified outcome priorities and multiplicity methods when many measures are considered. Without reported results and analysis methods, secondary endpoints cannot clarify the primary comparison. The trial therefore offers a useful example of how registry summaries can describe a study and its observed measures while leaving key inferential questions unresolved.

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 gives limited information about how the study was conducted and analyzed. It identifies randomization, double masking and a parallel design, but does not describe the randomization procedure, allocation concealment, masking roles, or statistical analysis plan. The sample-size justification is not reported, and the record does not give a prespecified equivalence margin.

For the primary endpoint, the record reports group medians and inter-quartile range endpoints, but no between-group contrast, confidence interval, hypothesis test or equivalence decision. The primary population description notes exclusions for blood-collection timing and adverse events, while leaving the broader missing-data process and sensitivity analyses unreported. These gaps make it difficult to judge the precision and robustness of the comparison.

Although multiple secondary outcomes are named, analysis results for them are not reported in the available record, and the registry lists zero analyses. A strategy for handling multiplicity is also not reported. Safety information is similarly limited: group-level serious and other adverse-event counts are given, but the record does not provide detailed event descriptions, follow-up information or deaths; deaths are not reported in the registry record. The serious-event term Collapse is listed without a group attribution in the available information.

These limitations concern what the registry record reports. They do not establish that the study lacked procedures or analyses; those details are simply not reported in the registry record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Comparative Evaluation of Pharmacokinetics and Safety of BCD-055 and Remicade in Patients With Ankylosing Spondylitis — NCT02359903.
• Registry record last updated 2016-06-08; status last verified 2016-05.
• Results first posted 2016-06-08.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT02359903 is a completed, randomized, double-blind, parallel-group phase 1 study sponsored by Biocad. It compared BCD-055 with Remicade in patients with ankylosing spondylitis, using the stated 5 mg/kg slow intravenous infusion schedule on weeks 0, 2, 6, 14 and 22. The registry lists enrollment of 90.

The primary endpoint was area under the plasma concentration-time curve from 0 hours to 336 hours after a single infusion, reported as a median and inter-quartile range. The record gives group medians and interval endpoints but no formal equivalence analysis, confidence interval or equivalence margin. It also names secondary pharmacokinetic and ASAS20 outcomes, without analysis results in the available record. Safety counts are reported, but detailed event information is limited. The registry record therefore supports a descriptive account of the reported findings, while leaving formal equivalence and broader comparative conclusions unresolved.