A PK Study Comparing MB05, EU-sourced Synagis® and US-sourced Synagis® in Healthy Volunteers.: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A PK Study Comparing MB05, EU-sourced Synagis® and US-sourced Synagis® in Healthy Volunteers. (NCT05121246), a randomized phase 1 study. The primary outcome is Comparison of the Pharmacokinetic (PK) Profiles Between MB05 and EU-Synagis®, Between MB05 and US-Synagis® and Between EU-Synagis® and US-Synagis® in Terms of Area Under the Serum Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf).

2. Clinical Question

The study also planned to assess Cmax, other pharmacokinetic measures, safety, tolerability, and immunogenicity. Its stated purpose was to compare drug levels in blood after administration across the three arms. The registry identifies the study as phase 1, randomized, triple-masked, and parallel-group, and lists healthy volunteers as the condition. These design features frame the question as a comparison of pharmacokinetic profiles under the study conditions, rather than an assessment of clinical benefit in a patient population.

3. Trial Design

This was a randomized, triple-masked, parallel-group phase 1 study sponsored by mAbxience Research S.L. The registry lists enrollment of 150 healthy volunteers and describes three arms: MB05, EU-Synagis®, and US-Synagis®. Each arm received a single intramuscular injection of 3mg/kg on day 1. The record is marked completed. The listed study dates are 2022-06-15 for start and 2023-03-31 for primary completion.

The main comparison concerned pharmacokinetics, with the primary endpoint specified as AUC0-inf. Cmax was also included in the described bioequivalence assessment. Blood sampling was scheduled before dosing, at several early post-dose timepoints, and on later study days through day 99. This schedule was intended to capture drug concentrations over time, which are used to characterize pharmacokinetic profiles. The registry also lists Tmax, t1/2, Vz, CL, safety and tolerability, and immunogenicity as secondary outcome areas.

For the primary analysis, the registry describes analysis of variance applied to log-transformed pharmacokinetic parameter values. Pairwise comparisons were planned among MB05 and each Synagis® source, and between the two Synagis® sources. The stated equivalence criterion was that the 90% confidence intervals for ratios of least squares geometric means fall within 80.00% to 125.00%. The record identifies a pharmacokinetic population based on randomized participants with sufficient data for reliable AUC0-inf estimates. More detail on randomization procedures, masking implementation, the full analysis plan, and the rationale for the enrollment target is not reported in the registry record.

4. Participant Flow and Accounting

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

Before assignment: A total of 150 subjects were enrolled into the study, of those, 9 subjects were randomized but not dosed for reasons outlined as follows: * Five subjects were unable to be dosed due to dosing delays at the site. These subjects were discharged from the clinical unit as eligible; * One subject was not dosed due a randomization error; * One subject did not meet inclusion criterion #9 ; * Two subjects did not meet inclusion criteria #4

Overall Study

Analysis population for the primary outcome, as defined in the registry: The PK population will include all randomized participants where there is sufficient data for reliable estimates of AUC0-inf (as determined by the study Pharmacokineticist).

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: Of 150 subjects enrolled, a total of 9 subjects were randomized but did not receive a dose of IP, for reasons outlined as follows: * Five subjects were unable to be dosed due to dosing delays at the site. These subjects were discharged from the clinical unit as eligible; * One subject was not dosed due a randomization error; * One subject did not meet inclusion criterion #9; * Two subjects did not meet inclusion criteria #4

6. Primary Endpoint

The registry lists the primary outcome as Comparison of the Pharmacokinetic (PK) Profiles Between MB05 and EU-Synagis®, Between MB05 and US-Synagis® and Between EU-Synagis® and US-Synagis® in Terms of Area Under the Serum Concentration Versus Time Curve From Time Zero to Infinity (AUC0-inf), measured over Day 1 - Day 100.

AUC0-inf is the area under the serum concentration-versus-time curve from time zero extrapolated to infinity. In general, an area-under-the-curve measure combines concentration information across the sampling period and is used to characterize overall drug exposure. Extrapolation to infinity estimates the portion of exposure beyond the observed sampling period; the registry’s definition of the pharmacokinetic population makes sufficient data for a reliable AUC0-inf estimate a condition for inclusion in that population.

The primary endpoint compares AUC0-inf between treatment pairs using ratios of geometric least squares means. A ratio expresses one group’s estimated exposure relative to the other group’s, with 100% representing equality of the estimates. The registry specifies analysis of variance on log-transformed pharmacokinetic values and uses a 90% confidence interval around each ratio. In general, log transformation is commonly used for pharmacokinetic measures whose comparisons are naturally expressed as ratios, and the resulting interval communicates the uncertainty around the estimated relative exposure.

The registry defines equivalence using an interval-bounds criterion: the full 90% confidence interval must lie within 80.00% to 125.00%. This is different from asking only whether a conventional test detects a difference. The criterion focuses on whether the data are sufficiently precise to place the entire interval inside prespecified bounds. The endpoint is therefore suited to the stated comparison of pharmacokinetic similarity, but it does not by itself answer questions about clinical outcomes or establish that the products have identical effects in every respect.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry’s primary analysis is framed as an equivalence assessment. In general, equivalence testing asks whether the observed difference between treatments is small enough, with sufficient precision, to fall within prespecified limits. This differs from a conventional difference test, where failure to detect a difference does not demonstrate that treatments are sufficiently similar. The registry specifies equivalence bounds of 80.00% to 125.00% for the ratio of least squares geometric means and says equivalence is concluded when the entire 90% confidence interval is contained within those bounds.

Why analyze ratios on a log scale?

The primary outcome is a ratio of geometric least squares means, and the registry describes analysis of variance using log-transformed pharmacokinetic parameter values. In general, a ratio is a natural way to express relative exposure: the comparison is scaled to the reference group rather than expressed as an absolute difference in concentration-time area. Taking logarithms turns multiplicative relationships into additive ones for statistical modeling. After analysis, estimates can be expressed back on the ratio scale, which makes comparison with the stated percentage bounds straightforward. The registry does not report further details of the model, such as its full specification or any covariates.

What does a 90% confidence interval say?

In general, a confidence interval describes uncertainty in an estimate under the statistical model and sampling process. A narrower interval indicates greater precision, while a wider interval indicates more uncertainty. It is not a statement that a particular probability attaches to the fixed, observed interval containing the true value. For this trial, the interval is assessed against equivalence limits, so its endpoints matter as much as the point estimate. An interval that crosses a limit does not satisfy the stated rule even if its central estimate is inside the bounds. Conversely, satisfying the interval rule is a statistical finding about the prespecified pharmacokinetic comparison, not a claim of identity in every possible feature.

Why does the registry specify sampling over time?

Drug concentration measurements at planned timepoints form the data used to estimate pharmacokinetic parameters. AUC0-inf represents exposure over time, while Cmax represents the maximum observed concentration measure in the planned analysis. The registry describes collections from pre-dose through day 99, including early post-dose collections and later study-day collections. In general, the timing and completeness of samples can affect the estimation of concentration-time parameters. The record does not report detailed rules for handling missed samples, below-quantification measurements, or the extrapolated portion of AUC0-inf beyond what is stated in its population definition.

How should the secondary comparisons be treated?

The posted secondary comparisons for t1/2, Vz, and CL include estimates, confidence intervals, and unadjusted p-values. These are recalculated, unadjusted comparisons from posted summary statistics, rather than the sponsor’s reported analysis; the registry’s reported analyses list does not contain a secondary analysis method or result. In general, unadjusted p-values do not account for the number of endpoints or comparisons examined. When many comparisons are considered, the chance of observing apparently unusual results can increase, so secondary findings are commonly treated as exploratory unless an analysis plan specifies how multiplicity is handled. The registry record does not report such a plan.

The accompanying sample-size illustrations are planning calculations based on the observed effects, not observed power and not the study’s own design justification. In general, these calculations show how a hypothetical future comparison’s participant requirement would change under stated assumptions about the effect to detect, significance level, allocation, and approximation. The registry gives the assumptions for these illustrations, but its sample-size justification for the trial itself is not reported in the registry record. Estimates based on very small observed effects can yield extremely large planning requirements; estimates based on unusually large observed effects can yield very small requirements. Such values should be interpreted cautiously because observed effects are uncertain and may not represent the effect a future study should be designed to detect.

The registry also identifies the AUC0-inf analysis population as randomized participants with enough data for reliable estimates, according to the study Pharmacokineticist. In general, restricting an analysis to participants with usable measurements can affect how results relate to all randomized participants, particularly if data availability is associated with treatment or participant characteristics. The record does not explain the criteria used to decide whether data were sufficient, how exclusions were handled, or whether another analysis population was used as a sensitivity check. The analysis population definition and the reported confidence intervals are therefore important context when reading the primary comparisons.

10. Multiplicity, Missing Data and Analysis Populations

The registry describes three pairwise primary comparisons and gives an equivalence rule for the AUC0-inf confidence intervals. It also describes assessment of Cmax and lists several secondary outcome areas. The record does not report whether the primary comparisons or the broader set of outcomes were handled with a multiplicity adjustment, a hierarchical testing strategy, or another prespecified procedure. Without that information, the degree to which the reported tests were intended to control error across multiple comparisons is not reported in the registry record.

The primary AUC0-inf estimates are presented with 90% confidence intervals and can be assessed against the registry’s stated equivalence bounds. The secondary p-values are unadjusted recalculations from summary statistics and are not reported sponsor analyses. In general, unadjusted results across multiple endpoints and comparisons are more appropriately treated as exploratory because the chance of at least one apparently unusual finding increases as the number of opportunities to find one grows. The registry does not report a broader statistical analysis plan that would clarify how these results were to be interpreted collectively.

For the primary pharmacokinetic population, the registry states that randomized participants were included when there was sufficient data for reliable AUC0-inf estimates, as determined by the study Pharmacokineticist. It does not report detailed missing-data procedures, the operational threshold for sufficient data, reasons for any exclusions, or an imputation approach. Nor does the record describe sensitivity analyses to assess the influence of missing or unusable pharmacokinetic observations. These omissions limit assessment of how robust the estimates are to data availability and population definition.

The registry does not report the sample-size justification or the assumptions underlying the enrollment target. The planning illustrations associated with recalculated secondary comparisons are explicitly not the trial’s design calculation. Information about interim analyses is not reported in the registry record. These gaps mean that the posted results can be interpreted using the stated endpoint and interval criterion, but the record does not provide a complete account of the broader prespecified analysis strategy.

11. 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 5% reporting threshold.

The posted serious adverse event figures are zero in each of the three groups. The registry lists 46 participants at risk in the MB05 group, 48 in the EU-Synagis® group, and 47 in the US-Synagis® group for these figures. No serious adverse event terms are listed. The death count is also zero in each group.

These entries describe the serious adverse events recorded in the registry, not every possible aspect of safety. In general, a zero count in a study group does not establish that an event is impossible or that two treatments have identical safety profiles. Safety interpretation depends on the events collected, the follow-up period, definitions, completeness of reporting, and the size and characteristics of the study population. The registry describes the study as evaluating safety and tolerability throughout, but detailed non-serious adverse-event results are not reported in the registry record.

The figures should therefore be read narrowly: no serious adverse events or deaths are recorded in the posted group summaries, and no serious event terms are listed. They do not support broader conclusions about uncommon harms or safety in populations beyond the healthy volunteers studied.

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

The primary endpoint gives a comparison of relative AUC0-inf exposure among MB05, EU-sourced Synagis®, and US-sourced Synagis®. Applying the registry’s stated equivalence criterion, the MB05 versus US-Synagis® interval and the EU-Synagis® versus US-Synagis® interval fall within 80.00% to 125.00%. The MB05 versus EU-Synagis® interval extends beyond the upper bound and therefore does not meet that stated interval criterion. The differences among these pairwise results matter: a finding for one comparison cannot automatically be extended to the other comparisons.

This is a pharmacokinetic result from a phase 1 study in healthy volunteers after a single intramuscular dose. It is not a direct measure of clinical effectiveness, and the study description does not establish how the results apply to patients, repeated dosing, or clinical outcomes. Pharmacokinetic similarity on AUC0-inf is one defined comparison, not a claim that every characteristic of the products is identical.

The registry also lists safety, tolerability, and immunogenicity as areas of interest. The posted serious adverse event summaries contain no serious events or deaths, but detailed non-serious safety findings and numerical immunogenicity findings are not reported in the registry record. The absence of those results from the record limits what can be concluded about those outcome areas. Similarly, the listed secondary pharmacokinetic measures add descriptive context but do not supplant the primary endpoint or its interval rule.

Confidence intervals communicate how precisely the relative exposure estimates are known under the analysis. The point estimates are near 100%, but the primary decision criterion depends on whether each entire interval fits inside the equivalence limits. One interval does not, while the other two do. The appropriate reading is therefore comparison-specific and restricted to the endpoint, population, dose, and follow-up described in the registry. It does not establish that treatment works or does not work, nor does it settle questions not measured by this study.

13. Why This Trial Matters Statistically

This study illustrates why equivalence questions require more than comparing point estimates or asking whether a conventional difference test is statistically significant. The registry sets explicit limits for the AUC0-inf ratio and requires the full 90% confidence interval to remain inside them. The posted results include one pairwise interval that extends beyond a limit and two that remain within the stated bounds. This makes the distinction between an estimate’s center and its precision concrete: a central estimate near 100% does not by itself satisfy an equivalence rule.

The three-arm design also makes the comparison structure important. MB05 is compared separately with EU-sourced and US-sourced Synagis®, and the two Synagis® sources are compared with each other. Those are distinct questions, and the results should be read pair by pair rather than collapsed into a single statement about all products. This is particularly relevant when the endpoints use confidence-interval criteria rather than a single overall test.

The record further demonstrates the need to distinguish primary analyses from secondary, unadjusted recalculations. Secondary estimates can describe aspects of pharmacokinetics, yet multiple outcomes and comparisons raise questions about multiplicity and confirmatory status. Where the analysis plan and adjustment strategy are not reported, restraint is needed in assigning weight to isolated secondary results.

Finally, this trial emphasizes the boundaries of statistical interpretation. A phase 1 pharmacokinetic study in healthy volunteers can address defined exposure comparisons under its study conditions. It does not by itself answer clinical benefit questions, establish safety in broader populations, or resolve unreported outcomes. The endpoint definition, analysis population, confidence intervals, and gaps in registry reporting all help determine what the data can support.

14. Limitations

• The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
• Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.

Several limitations are specific to the information available for this study. The primary result is reported for AUC0-inf, and the registry’s stated decision rule is tied to confidence intervals for that parameter. Although Cmax is mentioned in the bioequivalence description, corresponding posted numerical results are not included in the record summarized by these results. Numerical findings for Tmax and immunogenicity are also not reported in the registry record. This restricts assessment of the broader outcome set described in the study.

The pharmacokinetic population depends on sufficient data for reliable AUC0-inf estimates, as judged by the study Pharmacokineticist. The record does not give the detailed sufficiency criteria, the number excluded under them, reasons for missing or unusable samples, or sensitivity analyses. The comparison rows list their own analysis counts, but the registry does not explain in detail how those counts relate to enrollment or the population definition. This makes it difficult to assess selection effects from the information recorded.

The registry gives the primary analysis approach and equivalence bounds, but a full statistical analysis plan, multiplicity strategy, and interim-analysis information are not reported in the registry record. The sample-size justification for the trial is also not reported. Consequently, the posted secondary comparisons and planning illustrations should not be mistaken for prespecified sponsor conclusions or the trial’s original design assumptions.

Safety reporting in the available summary is limited to serious adverse event and death counts; detailed non-serious adverse events are not reported in the registry record. Follow-up and dosing were defined for this single-dose study in healthy volunteers, so the findings have a narrow context. These limitations do not change the stated AUC0-inf intervals, but they constrain the scope of conclusions that can be drawn from the record.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A PK Study Comparing MB05, EU-sourced Synagis® and US-sourced Synagis® in Healthy Volunteers. — NCT05121246.
• Registry record last updated 2025-04-02; status last verified 2023-09.
• Results first posted 2025-04-02.
• Data retrieved from ClinicalTrials.gov on 2026-11-09.
• Group sizes, means, event counts and sponsor-reported p-values are reproduced as posted. Effect estimates, confidence intervals and p-values not attributed to the sponsor are independently calculated from the posted summary statistics.

18. Record Summary

NCT05121246 is a completed, randomized, triple-masked, parallel-group phase 1 study sponsored by mAbxience Research S.L. It enrolled healthy volunteers and compared single-dose intramuscular MB05, EU-sourced Synagis®, and US-sourced Synagis®. Each arm received 3mg/kg on day 1.

The primary endpoint compared AUC0-inf ratios using 90% confidence intervals and an equivalence range of 80.00% to 125.00%. The MB05 versus EU-Synagis® interval extended beyond the upper bound; the MB05 versus US-Synagis® and EU-Synagis® versus US-Synagis® intervals were within the stated range. The registry also lists Cmax, additional pharmacokinetic outcomes, safety, tolerability, and immunogenicity, though several detailed results and analysis-plan elements are not reported in the registry record.