A Study Comparing the Pharmacokinetic Similarity of MB02-SP, MB02-DM and US Licensed-Avastin®.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study Comparing the Pharmacokinetic Similarity of MB02-SP, MB02-DM and US Licensed-Avastin®. (NCT04408989), a randomized phase 1 study. The primary outcome is Pharmacokinetics (PK) - (AUC[0-∞]).

2. Clinical Question

3. Trial Design

This was a randomized, double-blind, parallel-group, single-dose phase 1 study. The registry describes three arms: MB02-SP, MB02-DM and US-licensed Avastin®. The record lists triple masking, but does not identify which groups of people were masked. The trial was sponsored by mAbxience Research S.L. and is recorded as completed.

The record lists 114 participants enrolled. Each arm used the same described dose and administration: a single 1mg/kg dose, delivered as a 90-minute infusion on day 1. The study population was healthy male volunteers, rather than patients receiving treatment for a disease. The registry does not report further eligibility criteria in the registry record for this summary.

The main objective was to compare pharmacokinetics, with safety and immunogenicity also assessed. Blood sampling for pharmacokinetic assessment began before dosing and included the end of infusion, multiple early post-dose timepoints, and later follow-up through Day 100 post-dose. The listed secondary outcomes include Tmax, AUC[0 t], clearance, half-life, immunogenicity and safety measures. The registry lists 9 outcome measures and 6 analyses, but further details of the analyses are not reported in the registry record.

The primary pharmacokinetic analysis used a defined population: participants who received the full dose, had no major protocol deviations and had evaluable pharmacokinetic data for at least one timepoint. The arm counts reported for that outcome are 37, 39 and 38. These are outcome-specific counts and should not be confused with the overall enrollment. The registry record does not report the allocation ratio or the method used to generate the random sequence.

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: The PK population included all subjects who received the full dose of MB02-SP, MB02-DM or US-Avastin®, did not had any major protocol deviations, and had evaluable PK data for at least one timepoint

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.

6. Primary Endpoint

The registry lists the primary outcome as Pharmacokinetics (PK) - (AUC[0-∞]), measured over Pre-dose (0 hours),end of infusion, 2, 3, 4, 5, 6, 7, 12, and 24 hours and at Days 3, 4, 5, 6, 7, 8, 10, 14, 21, 28, 42, 56, 78, and 100 post-dose.

AUC[0-∞] represents the area under the curve describing drug concentration in the blood over time, from dosing through the extrapolated end of the concentration profile. It is expressed in h*ng/ml. In general, AUC is used to summarize overall systemic drug exposure, rather than a concentration at only one sampling time. Extending the measure to infinity allows the profile after the last observed concentration to contribute through an extrapolated portion.

The registry reports the endpoint as a geometric mean, with geometric coefficient of variation as the dispersion measure. In general, pharmacokinetic measures are often analyzed on a logarithmic scale because their distributions may be skewed; estimates on that scale can be transformed back to ratios for comparison. The registry’s posted pairwise results are ratios of geometric least-squares means, which describe relative exposure between arms.

The endpoint was assessed using blood sampling before dosing, at the end of infusion, at several early timepoints and at follow-up visits through Day 100 post-dose. The record does not report the precise method for estimating the extrapolated part of AUC, the handling of concentrations below quantification limits, or the model used to obtain the geometric least-squares means. Those details are not reported in the registry record.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The main reported comparison is based on ratios of geometric least-squares means. In general, a geometric mean is useful when a measure is positive and its distribution is asymmetric: analysis on a logarithmic scale can make relative differences more suitable for modeling. A ratio puts the comparison on a relative scale. A ratio of 1 represents equal estimated geometric means; values on either side indicate relative differences. The registry does not state the specific model or adjustment used to obtain its geometric least-squares means.

What does the confidence interval describe?

In general, a confidence interval expresses uncertainty about an estimate under a statistical model and repeated-sampling framework. A 90% confidence interval is not a probability statement that the particular interval contains the true value. It gives a range of values compatible with the data and the model at the stated confidence level. The intervals reported for the three comparisons are 0.899 to 0.989, 0.956 to 1.05, and 1.01 to 1.12, respectively.

For an equivalence question, the interval is interpreted in relation to prespecified limits. The aim is to determine whether the plausible relative differences fall within an acceptable range, rather than simply whether a conventional test finds evidence of a difference. Those limits are not reported in the registry record. Nor does the record describe whether the primary conclusion required both one-sided tests, an interval-based rule, or another specified procedure. Without these details, the confidence intervals should be read as estimates of relative exposure with uncertainty, not as a complete demonstration of a formal equivalence decision.

Why use geometric summaries?

In general, pharmacokinetic quantities such as exposure are positive and can vary multiplicatively. A logarithmic analysis can be appropriate when proportional changes matter more than absolute changes. After analysis on the log scale, transforming the estimate back produces a geometric mean or a ratio of geometric means. The geometric coefficient of variation describes relative variability on a multiplicative scale. The registry identifies that dispersion measure for the primary endpoint, but does not provide its calculation method.

The arm-specific geometric means are reported alongside the geometric coefficients of variation. These summaries describe each arm, while the pairwise ratio estimates directly compare arms. A descriptive difference between two arm summaries is not itself the trial’s adjusted comparative analysis. The registry does not report the model specification, covariates, or any sensitivity analyses that might clarify how the comparative estimates were obtained.

How should the sampling schedule be understood?

The primary endpoint was constructed from concentrations measured across a schedule beginning before dosing and extending through Day 100 post-dose. In general, dense early sampling helps describe the concentration profile around and after an infusion, while later sampling contributes information about the declining portion of the profile. AUC[0-∞] includes an extrapolated component beyond the observed concentration data. The registry does not report how much of the estimated AUC was extrapolated or the rules used to calculate that component.

What does the analysis population mean?

The primary pharmacokinetic population included participants who received the full dose, had no major protocol deviations, and had evaluable pharmacokinetic data for at least one timepoint. This is a defined analysis population, not necessarily every randomized participant. The registry reports outcome counts of 37 for MB02-SP, 39 for MB02-DM and 38 for US-licensed Avastin®. The record does not report how many participants were randomized to each arm, whether any were excluded from this population, or the reasons for any exclusions.

In general, restricting a pharmacokinetic analysis to participants with usable exposure data can make the endpoint estimable, but it can also mean that the analysis does not preserve all the features of randomization if exclusions differ between groups. Whether that concern applies depends on the actual exclusions and their reasons, which are not reported in the registry record. The trial’s protocol, statistical analysis plan, model details, missing-data procedures and sensitivity analyses are also not reported in the registry record.

10. Analyses Reported by the Sponsor

The registry reports the pairwise pharmacokinetic estimates as ratios of geometric least-squares means with 90% confidence intervals. Those are the posted comparative results for the primary endpoint. The registry record does not identify a separate recalculated estimate or give enough model detail to reproduce the sponsor’s analysis from the summary statistics alone.

The record does not flag a discrepancy between the reported analysis and a recalculation. That absence does not add information about the underlying model or its assumptions. The sponsor’s reported analysis remains the relevant trial analysis; an unadjusted recalculation from arm-level summary statistics, if available, would not replace it because it may not use the same model, analysis population or handling of the data.

The intervals and point estimates can be read as the posted estimates of relative exposure for the three arm pairs. However, the equivalence margins and the formal decision rule are not reported in the registry record. It is therefore not possible to infer the sponsor’s formal equivalence conclusion from the ratios alone. No sample-size illustration values are reported in the registry record for this account; any such planning illustration is distinct from observed trial evidence and is not observed power.

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary pharmacokinetic endpoint and several secondary outcome areas, including other pharmacokinetic parameters, immunogenicity and safety. It also lists 9 outcome measures and 6 analyses. Multiple outcomes and pairwise comparisons raise a general statistical issue: the more inferences made, the greater the chance that at least one result may appear notable by chance if no adjustment or hierarchy is used.

The record does not report a multiplicity-control procedure, a testing hierarchy, or which outcomes were considered confirmatory versus exploratory. The three primary-endpoint pairwise comparisons are all posted with 90% confidence intervals, but the record does not explain how those comparisons relate to the overall decision rule. It would be inappropriate to assume that an adjustment was or was not applied.

Missing-data handling is also not described in the registry record. The primary analysis population required evaluable pharmacokinetic data for at least one timepoint, but that description does not specify how missing concentrations, incomplete profiles, below-quantification measurements or missing follow-up visits were handled. The registry does not report sensitivity analyses addressing missing data or departures from the analysis assumptions.

The analysis population is described as participants who received the full dose, had no major protocol deviations and had evaluable pharmacokinetic data for at least one timepoint. The number randomized by arm, exclusions from that population, and reasons for exclusion are not reported in the registry record. Without those details, readers cannot fully assess how the analyzed groups relate to the randomized groups. The record also does not report a protocol or statistical analysis plan that would clarify whether these choices were prespecified.

12. Safety Results

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

Deaths

Other (non-serious) adverse events

Participants with at least one non-serious event at or above the registry's 4% reporting threshold.

Most frequent non-serious adverse event terms

The registry reports no serious adverse events in any of the three arms: 0 of 37 participants at risk for MB02-SP, 0 of 39 for MB02-DM and 0 of 38 for US-licensed Avastin®. It also reports 0 deaths in each arm. These are the posted serious-event and death counts during the recorded safety assessment.

For other adverse events, the reported affected-participant counts are 14 of 37 for MB02-SP, 22 of 39 for MB02-DM and 24 of 38 for US-licensed Avastin®. The registry also lists treatment-related adverse events as a secondary safety outcome, but the adverse-event counts do not establish how each event was classified or related to treatment. The detailed event terms and severity distributions are not reported in the registry record.

In general, zero observed serious events in a group does not establish that the underlying risk is zero. Safety estimates from a study of this size and duration can be imprecise, and this study involved a single dose in healthy male volunteers. The posted counts describe what was observed in this study; they do not determine the frequency of events in other populations, with other dosing, or over other follow-up periods.

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

The results provide comparative pharmacokinetic estimates for MB02-SP, MB02-DM and US-licensed Avastin® in healthy male volunteers after a single 1mg/kg infusion. The primary measure, AUC[0-∞], summarizes overall drug exposure. The registry reports ratios of geometric least-squares means and 90% confidence intervals for all three pairs. These estimates and intervals describe the size and precision of the observed relative exposure comparisons.

The record labels the comparisons as equivalence analyses, but does not report the equivalence margins or the decision rule. A reader therefore cannot determine from the registry information alone whether each comparison met the prespecified criterion. A point estimate near 1 is not, on its own, proof of equivalence; the interval and its relation to the predefined margins are central to that judgment.

These results do not establish comparative clinical outcomes in patients. The study was conducted in healthy male volunteers, used a single dose, and measured pharmacokinetics, safety and immunogenicity. It does not answer questions about effectiveness in a disease population or about repeated administration. The posted adverse-event counts are descriptive for the observed study participants, not a guarantee about other settings.

The registry record also leaves important analytical details unspecified, including the statistical model, multiplicity procedures, missing-data handling, and sensitivity analyses. These omissions limit independent assessment of how the estimates were produced and how robust the conclusions are. The most direct interpretation is therefore bounded: the record gives pairwise exposure estimates with their reported uncertainty, while the formal equivalence criteria and broader clinical implications are not established by the posted information.

14. Why This Trial Matters Statistically

This study illustrates why a pharmacokinetic comparison is not interpreted in the same way as a conventional test for a difference. The posted endpoint is summarized by ratios of geometric least-squares means, and its uncertainty is expressed with 90% confidence intervals. For an equivalence question, those intervals must be judged against prespecified boundaries. Without the boundaries, readers can inspect the estimates but cannot independently verify the formal decision.

The three-arm design also makes the comparison structure important. The registry reports results for each pair of products rather than one single overall contrast. Each estimate answers a distinct relative-exposure question, and all three should be read alongside their confidence intervals and the analysis population definition. The record does not explain how the comparisons were prioritized or how multiplicity was addressed.

The study also demonstrates the difference between a trial’s primary analysis and a simple comparison of arm summaries. The arm-level geometric means provide descriptive context, while the reported ratios of geometric least-squares means are the direct comparative results. In general, a model-based estimate can incorporate analysis choices not recoverable from summary values alone, so a simple recalculation is not automatically a substitute.

Finally, the record distinguishes pharmacokinetic evidence from broader clinical evidence. A single-dose exposure comparison in healthy volunteers can characterize relative drug exposure under the study conditions. It does not, by itself, answer questions about clinical outcomes, longer-term use or other populations. Clear reporting of the analysis model, equivalence margins, exclusions and missing-data methods would make the statistical interpretation more complete.

15. 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 reports the primary endpoint and its pairwise estimates, but several details needed to assess the analysis are not reported in the registry record. These include the equivalence margins, the formal decision rule, the model specification, any covariate adjustment, and the method used to estimate the extrapolated portion of AUC[0-∞]. Without these details, the estimates can be described but the formal equivalence conclusion cannot be independently evaluated.

The primary analysis population excluded participants who did not meet the described full-dose, protocol-deviation and evaluable-data conditions. The record does not report the number randomized to each arm, the number excluded from the primary population, or the reasons. That limits assessment of whether exclusions could have affected comparability between randomized groups.

The record does not report methods for missing concentrations, incomplete pharmacokinetic profiles, below-quantification values, or sensitivity analyses. It also does not report procedures for multiplicity across the three pairwise comparisons and listed secondary outcomes. These are important gaps when assessing uncertainty and the scope of confirmatory inference.

Generalizability is limited by the recorded population and dosing conditions: healthy male volunteers received a single dose and were followed for pharmacokinetic sampling through Day 100 post-dose. The study does not provide patient clinical outcomes or evidence about repeated dosing in the registry record for this account. Safety counts are also descriptive and should be interpreted within the study population and follow-up recorded.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study Comparing the Pharmacokinetic Similarity of MB02-SP, MB02-DM and US Licensed-Avastin®. — NCT04408989.
• Registry record last updated 2024-09-19; status last verified 2022-06.
• Results first posted 2024-09-19.
• 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.

19. Record Summary

NCT04408989 is a completed, randomized, double-blind, parallel-group phase 1 study sponsored by mAbxience Research S.L. It enrolled 114 healthy male volunteers and compared single-dose MB02-SP, MB02-DM and US-licensed Avastin®.

The primary endpoint was AUC[0-∞], reported as geometric means with geometric coefficients of variation. The registry posts three pairwise ratios of geometric least-squares means with 90% confidence intervals. The outcome analysis population included participants who received the full dose, had no major protocol deviations and had evaluable pharmacokinetic data for at least one timepoint.

The registry labels the analyses as equivalence comparisons, but does not report the equivalence margins or decision rule. It also does not report several analysis details, including multiplicity procedures and missing-data methods. The posted results describe single-dose pharmacokinetic comparisons in healthy male volunteers; they do not establish clinical outcomes in patients.