Compare IBI305 and Bevacizumab on Pharmacokinetics/Safety/Immunogenicity on Healthy Male: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Compare IBI305 and Bevacizumab on Pharmacokinetics/Safety/Immunogenicity on Healthy Male (NCT03083990), a randomized phase 1 study. The primary outcome is AUC0 - t.

2. Clinical Question

The question is about drug exposure over time in healthy male subjects, rather than a clinical treatment outcome. AUC0 - t represents the area under the blood drug concentration-time curve from 0 to t. The registry lists blood sampling from before infusion through 85 days after infusion. It also lists secondary pharmacokinetic measures: maximum concentration, half-life, clearance rate and apparent volume of distribution.

This was a randomized, double-blind, parallel controlled Phase 1 study. The record describes one dose of each intervention and identifies healthy subjects as the condition. It does not report a patient population with the disease for which bevacizumab may be used, or clinical efficacy outcomes. Accordingly, the question addressed by this record is limited to pharmacokinetics and safety in the enrolled population; it does not directly answer questions about clinical outcomes in patients.

3. Trial Design

The registry record describes a randomized, double-blind, parallel controlled Phase 1 study sponsored by Innovent Biologics (Suzhou) Co. Ltd. It is marked completed. The recorded study start was 2017-03-09 and the primary completion date was 2017-08-17. Enrollment is listed as 100, and the study population is described as healthy male subjects.

One group received IBI305, 3mg/kg by intravenous infusion over 90 minutes. The other received bevacizumab (Avastin), also 3mg/kg by intravenous infusion over 90 minutes. The interventions were given as a single dose. Randomization assigns participants to groups by chance; double masking means the record identifies the study as masked, but it does not specify which study personnel or participants were masked. The registry also does not report details of the randomization procedure or how masking was maintained.

The study used a parallel design: participants were assigned to one intervention group rather than receiving both interventions in sequence. Pharmacokinetic sampling was scheduled before infusion, shortly after infusion, and at later timepoints through 85 days. The primary outcome is AUC0 - t. Secondary outcomes listed include Cmax, t1/2, clearance rate and apparent volume of distribution.

The record reports 50 subjects at risk for safety outcomes in each group. For the primary pharmacokinetic outcome, the analysis counts are 48 for IBI305 and 50 for bevacizumab; the registry notes that 2 subjects in the IBI305 arm were not included in the pharmacokinetic analysis set because of positive ADA at baseline. The record does not report a sample-size justification, allocation ratio rationale, detailed eligibility criteria, or an account of deviations from the intended intervention.

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: 2 subjects in the IBI305 arm were not included in the PKAS(PK analysis set) because of positive ADA at baseline

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: The baseline demographics of the subjects were analyzed based on the Pharmacokinetics analysis set.A total of 98 (98.0%) subjects were included , and 2 (4%) subjects in the IBI305 arm were excluded in the due to positive anti-drug antibody at baseline.

6. Primary Endpoint

The registry lists the primary outcome as AUC0 - t, measured over 60 min before intravenous infusion, 5 min after iv. infusion, 4 hr, 12 hr, 2 days, 3 days, 5 days, 8 days, 15 days, 22 days, 29 days, 43 days, 57 days, 64 days, 71 days, 85 days.

The primary endpoint is AUC0 - t, described in the registry as the area under the blood drug concentration-time curve from 0 to t. It is reported as a geometric mean in h*ug/mL. In general, an area-under-the-curve measure combines concentration information across the sampling period, representing drug exposure over time rather than concentration at a single sampling moment. The registry lists sampling from 60 minutes before intravenous infusion, through several post-infusion timepoints, to 85 days.

AUC is used in pharmacokinetic comparisons because an exposure profile may differ in its overall extent even when concentrations at an individual timepoint look alike. It complements outcomes such as Cmax, which describes maximum concentration, and t1/2, which describes half-life. Clearance and apparent volume of distribution characterize other aspects of how drug is handled and distributed.

The record gives a geometric mean of 19700 for IBI305 and 20740 for bevacizumab, with analysis counts of 48 and 50, respectively. It gives spreads of 18.8 and 19.1, labeled standard deviations. Two subjects in the IBI305 arm were excluded from the pharmacokinetic analysis set because of positive ADA at baseline. The record does not define the endpoint's terminal time t beyond the stated description, nor does it explain the reported spread scale. These details matter when interpreting the summaries and comparing them with the sponsor's reported analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does the primary endpoint capture?

AUC0 - t is an area-under-the-curve measure derived from blood drug concentration over time. As a general pharmacokinetic concept, the area summarizes exposure across the observed sampling interval, while Cmax focuses on the maximum concentration and half-life concerns the decline in concentration over time. The registry describes AUC0 - t as a geometric mean in h*ug/mL and lists samples from before infusion through 85 days. It does not further define t or give the method used to calculate the area.

The group summaries are geometric means of 19700 for IBI305 and 20740 for bevacizumab. The record labels the spread as standard deviation, giving 18.8 and 19.1. Because the record does not explain the scale on which those spreads were calculated, they should be read as reported rather than reinterpreted as a spread on the original measurement scale.

How should the sponsor's primary analysis be read?

The registry lists an ANOVA analysis, labels its parameter Odds Ratio (OR), and reports 0.950 with a 90% confidence interval from 0.892 to 1.012 and p >0.05. It identifies the analysis type as equivalence. The record does not explain why the parameter is labeled Odds Ratio (OR) for this pharmacokinetic endpoint, whether a transformation was used, or what equivalence margins were specified.

In general, a confidence interval describes uncertainty around an estimate under the analysis model. An equivalence assessment usually asks whether the interval is contained within prespecified limits on either side of a target value. The limits are essential to interpret the result; they are not reported in this registry record. A nonsignificant test of difference is not itself evidence of equivalence, because failure to detect a difference can also reflect limited precision. The reported p-value and interval must therefore be presented as the registry gives them, without inferring an equivalence margin or a stronger conclusion.

What do the recalculated secondary comparisons estimate?

The secondary recalculations are unadjusted comparisons of group means using posted summary statistics. They give mean differences, confidence intervals and unadjusted p-values for t1/2, clearance rate and apparent volume of distribution. A mean difference is the difference between the two reported group means, expressed in the endpoint's units. A confidence interval communicates uncertainty around that estimated difference. When an interval includes zero, the summaries are compatible with no mean difference as well as with differences in either direction; this does not prove that the groups are equivalent.

As a general statistical point, standard errors quantify uncertainty in an estimated mean, and the precision of a difference depends on the uncertainty in both groups. The recalculations use the posted group sizes and spreads; the record marks the pooled standard deviations as not approximated. Their results are supplementary calculations, not the sponsor's reported primary analysis. The reported analyses for these secondary endpoints are empty in the registry record, so the recalculations should not be described as sponsor analyses.

Why does multiplicity matter?

Several pharmacokinetic outcomes are listed, and the record identifies multiple outcome measures and analyses. When many outcomes are examined, the chance of observing a nominally unusual result by chance can increase. As a general statistical principle, a prespecified multiplicity strategy can control how results across several tests are interpreted. The registry record does not report a multiplicity adjustment, a confirmatory hierarchy, or which secondary comparisons were planned as confirmatory. Accordingly, the unadjusted secondary p-values are descriptive evidence, not a set of independent confirmations.

The listed secondary estimates should be interpreted alongside their intervals and the primary analysis, not as stand-alone declarations of similarity or difference. The absence of a reported adjustment does not show that none was used in the full study analysis; it means the registry record does not document one.

What do the planning illustrations mean?

The sample-size illustrations are based on observed effects, not on the study's own design rationale. Their stated assumptions are a two-sided significance level of 0.05, equal allocation, a normal approximation, and an effect to detect defined as a stated fraction of the observed effect. They describe participants per arm for target power levels; they are not observed power and do not establish that this study was designed around those effects.

In general, a planning calculation asks how much information a future study might need to detect an assumed effect under stated assumptions. If the assumed effect is smaller, the required sample size tends to be larger. These illustrations inherit uncertainty from the observed effect and from the assumptions used. The registry does not report the trial's own sample-size justification, target power, or design effect assumption, so the illustrations should not be mistaken for the original protocol plan.

For safety interpretation, the record gives counts of serious and other adverse events and deaths by group. Such counts are descriptive. They do not alone establish causation, and without event-level detail, follow-up context or an analysis plan, they cannot resolve differences in risk. The record reports a serious adverse event term among the top terms, but does not provide enough context to infer its relationship to treatment.

10. Analyses Reported by the Sponsor

The sponsor-reported primary analysis is labeled ANOVA and equivalence. The registry identifies its parameter as Odds Ratio (OR) and reports an estimate of 0.950, a 90% confidence interval from 0.892 to 1.012, and p >0.05. The record does not explain the parameter label or provide the equivalence margins, so the estimate and interval cannot be used to independently verify an equivalence conclusion from the registry information alone.

The group-level AUC0 - t summaries are geometric means of 19700 for IBI305 and 20740 for bevacizumab. The recalculated secondary comparisons concern different endpoints and are simple, unadjusted re-calculations from posted summary statistics. They are not a recalculation of the sponsor's primary analysis. The record reports no discrepancy between the posted primary analysis and the calculations, but the available information is insufficient to reproduce the sponsor analysis in detail.

The reported p-value greater than 0.05 should not be read as proof that the interventions are equivalent. In general, equivalence depends on a prespecified margin and an interval judged against that margin. Since the margin and supporting analysis details are not reported in the registry record, the sponsor's stated equivalence analysis can be described, but its criteria cannot be independently assessed from this record.

11. Multiplicity, Missing Data and Analysis Populations

The record lists one primary outcome and several secondary pharmacokinetic outcomes, and it reports multiple analyses. The primary measure is AUC0 - t. Secondary measures named in the record include Cmax, t1/2, clearance rate and apparent volume of distribution. The record does not report whether a hierarchy was used to order these outcomes, whether any secondary outcomes were confirmatory, or whether the analysis adjusted for multiple comparisons.

As a general statistical principle, testing multiple outcomes without adjustment can increase the chance that at least one result appears unusual by chance. An adjustment or prespecified testing sequence can guide interpretation across outcomes. Because the registry does not describe such a strategy, the recalculated secondary p-values should be treated as unadjusted and exploratory rather than as independent confirmatory findings. Their confidence intervals remain useful for understanding the range of differences compatible with the calculations, but they do not resolve the multiplicity issue.

The record reports that 2 subjects in the IBI305 arm were not included in the pharmacokinetic analysis set because of positive ADA at baseline. It reports primary analysis counts of 48 for IBI305 and 50 for bevacizumab, and safety counts at risk of 50 in each group. It does not report the full analysis-population definitions, whether an intention-to-treat analysis was conducted, how missing pharmacokinetic observations were handled, or whether any additional exclusions occurred. The available information therefore cannot establish the extent or potential impact of missing data beyond the stated baseline ADA exclusions.

The record does not report interim analyses, a missing-data sensitivity analysis, or a detailed statistical analysis plan. It also does not report the equivalence margins needed to assess the sponsor's stated equivalence analysis. These omissions limit assessment of how the analysis was prespecified and whether the reported results are robust to alternative assumptions. They should be understood as limitations of what is documented in the registry record, not as evidence that those procedures were absent from the full study conduct.

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 5% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: hand injury (2.0%).

The safety record lists 50 subjects at risk in each group. It reports one serious adverse event in the IBI305 group and none in the bevacizumab group. The number of deaths is zero in each group. The top serious adverse event term listed is hand injury, at 2.0%; the record does not provide enough detail to assign that term to a group or assess its context.

The record also lists 40 other adverse events in each group. These are counts, not evidence that events were caused by either intervention. The information does not include a full description of event severity, timing, duration, relatedness assessment or individual event histories. The registry record also does not provide a safety analysis plan or enough follow-up detail to assess the ability to detect uncommon or delayed events.

These observations describe what was recorded in this study population. They should not be interpreted as a comparative safety conclusion or as evidence about safety in populations not enrolled in the trial.

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

The record documents a randomized, double-blind Phase 1 comparison of a single IBI305 infusion with a single bevacizumab infusion in healthy male subjects. It reports similar-scale AUC0 - t geometric mean summaries and a sponsor analysis labeled equivalence. It also provides secondary pharmacokinetic summaries and adverse-event counts. Together, these are evidence about pharmacokinetics and recorded safety events in the study setting.

The record does not by itself establish clinical efficacy, a treatment benefit, or outcomes in patients with a disease. It contains no clinical disease outcome as the primary endpoint. A pharmacokinetic comparison addresses exposure and related drug-handling measures, not whether a therapy improves health outcomes. The enrolled population and single-dose design also limit how far these results can be generalized to other populations, dosing schedules or settings.

The reported primary p-value is greater than 0.05, but this does not independently establish equivalence. The registry does not report the margins needed to interpret an equivalence interval, and it does not explain the Odds Ratio (OR) label for the primary AUC analysis. The recalculated secondary comparisons are unadjusted and do not replace that analysis. Their intervals include zero, but that is not proof that meaningful differences are absent.

The safety counts show few recorded serious events in these groups and no deaths, but they do not establish comparative safety. Event counts alone do not establish causation or rule out uncommon events. The registry record does not report sufficient detail to assess all potential safety concerns.

In short, the record supports a narrow description of pharmacokinetic summaries and recorded events after one dose in healthy male subjects. It does not resolve questions that require missing equivalence criteria, detailed analysis methods, broader clinical outcomes or evidence from other populations and dosing contexts.

14. Why This Trial Matters Statistically

This study illustrates why pharmacokinetic similarity claims require more than a visual comparison of group means or a nonsignificant difference test. The registry presents AUC0 - t geometric means and a sponsor analysis labeled equivalence, but the equivalence margins are not reported. Those margins define how much difference is considered acceptable for an equivalence assessment. Without them, readers cannot independently determine whether the reported interval meets the study's stated objective.

The primary parameter is labeled Odds Ratio (OR), although the endpoint is an AUC measure and the analysis is described as ANOVA. The record does not explain this presentation. That ambiguity demonstrates the importance of clear reporting of estimands, transformations, units, analysis populations and interpretation criteria. Clear definitions allow readers to connect a statistical estimate to the clinical or pharmacokinetic question it is intended to answer.

The study also makes a useful distinction between primary and secondary outcomes. Recalculated secondary comparisons can describe whether the posted summaries point in a similar direction, but unadjusted results from several endpoints cannot be treated as multiple confirmations. Intervals are important alongside p-values because they show uncertainty and the range of differences compatible with the data under the calculation assumptions.

Finally, the record documents an exclusion from the pharmacokinetic analysis set related to baseline ADA and reports separate safety counts. This reinforces the need to identify analysis populations and explain missing-data handling. These details affect which participants contribute to each outcome and how results should be interpreted. The record offers a compact case study in the value of transparent equivalence criteria, endpoint definitions, multiplicity plans and population descriptions.

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.

This trial's interpretation is limited by the information recorded about its primary analysis. The sponsor analysis is labeled equivalence, but the registry does not report the equivalence margins. It identifies the analysis parameter as Odds Ratio (OR) without explaining how that parameter relates to the AUC0 - t endpoint. It also does not provide enough detail to reproduce the sponsor's primary analysis.

The record does not define the terminal time t beyond describing AUC0 - t as the area under the blood concentration-time curve from 0 to t. It does not explain the scale for the reported standard deviations accompanying the geometric means. Those details would help readers assess the endpoint and its dispersion more fully.

The pharmacokinetic analysis excluded 2 subjects in the IBI305 arm because of positive ADA at baseline. The registry record does not describe the complete analysis populations, any other exclusions, the approach to missing observations, or sensitivity analyses. It also does not state whether an intention-to-treat analysis was performed. The effect of these analysis choices cannot be assessed from the recorded information.

For secondary outcomes, the record does not report a multiplicity strategy, a testing hierarchy or sponsor analyses for the listed outcomes. The posted recalculations are unadjusted and based on summary statistics. They are not substitutes for a prespecified analysis. Cmax is named as a secondary outcome, but no arm-level summary for it appears in the posted secondary results; the reason is not reported in the registry record.

The study enrolled healthy male subjects and used a single dose. This makes the findings specific to that study population and dosing context. The record does not report a sample-size justification, detailed eligibility criteria, randomization procedure or masking procedures. Safety information is also limited to event counts and a top serious event term, without sufficient detail to establish causation or characterize uncommon and delayed events.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Compare IBI305 and Bevacizumab on Pharmacokinetics/Safety/Immunogenicity on Healthy Male — NCT03083990.
• Registry record last updated 2020-11-27; status last verified 2020-11.
• Results first posted 2020-11-04.
• 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

NCT03083990 is a completed randomized, double-blind, parallel controlled Phase 1 study sponsored by Innovent Biologics (Suzhou) Co. Ltd. It compared a single 3mg/kg intravenous infusion of IBI305 with a single 3mg/kg intravenous infusion of bevacizumab (Avastin), each over 90 minutes, in healthy male subjects. The registry lists enrollment of 100.

The primary endpoint was AUC0 - t, a geometric-mean pharmacokinetic measure. The sponsor analysis is labeled equivalence and reports an estimate of 0.950 with a 90% confidence interval from 0.892 to 1.012 and p >0.05. Equivalence margins are not reported, limiting independent interpretation of that claim. The registry also records secondary pharmacokinetic outcomes and adverse-event counts. Two subjects in the IBI305 arm were excluded from the pharmacokinetic analysis set because of positive ADA at baseline.