Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease (NCT00397891), a randomized phase 1 study. The primary outcome is Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs).

2. Clinical Question

The clinical question is therefore primarily descriptive: what safety events and pharmacokinetic characteristics were recorded after single doses in this study population? The posted safety group counts give some information about participants with serious and other adverse events, but they do not include a reported treatment-effect estimate or uncertainty measure. The record does not establish whether the study was intended or designed to test a particular efficacy hypothesis. Its Phase 1 designation and stated focus are safety, tolerability, and pharmacokinetics, rather than a clinical benefit comparison.

3. Trial Design

The registry describes a Phase 1, randomized, double-blind, placebo-controlled, parallel-group study. Its official title characterizes the intervention as single ascending doses of AAB-001 in Japanese patients with mild to moderate Alzheimer’s disease. The brief summary likewise says the study evaluated safety, tolerability, and pharmacokinetics of single doses. The registry lists enrollment as 80 and status as completed. The study start is recorded as 2006-10 and primary completion as 2010-02.

The arm descriptions identify bapineuzumab doses of 0.15 mg/kg, 0.5 mg/kg, and 1.0 mg/kg, each or placebo. However, the adverse-event group information also lists a 2.0 mg/kg group. The registry record does not explain this difference, so the dose groups cannot be reconciled from the record alone. The intervention entries name bapineuzumab but do not provide further administration details.

Randomization can help balance participant characteristics across assigned groups, while masking is intended to limit the influence of treatment knowledge on participants’ experiences and outcome assessment. These are general purposes of the design features; the registry does not describe how randomization or masking was implemented, or whether masking was maintained throughout follow-up. The parallel-group label means participants are described as assigned to groups rather than undergoing a stated crossover, but the record does not give a detailed schedule of assessments or treatment administration.

The safety population is described as all randomized participants who received at least 1 dose of study medication. The registry does not report the randomized count by arm, withdrawals, or the number assessed at each time point. It lists pharmacokinetic secondary outcomes including maximum serum concentration, time to maximum concentration, area under the concentration curve, clearance, distribution volume, mean residence time, and serum decay half-life. Numerical results for these measures are 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.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Safety data set included all randomized participants who received at least 1 dose of study medication.

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: Safety data set included all randomized participants who received at least 1 dose of study medication.

6. Primary Endpoint

The registry lists the primary outcome as Number of Participants With Treatment-Emergent Adverse Events (AEs) or Serious Adverse Events (SAEs), measured over Baseline up to Week 52.

The primary endpoint is the number of participants with treatment-emergent adverse events or serious adverse events, measured from baseline up to Week 52. The record defines an adverse event as an untoward medical occurrence in someone who received study medication, regardless of whether it was considered caused by treatment. A serious adverse event is one associated with specified serious outcomes or considered significant for another reason. The record’s examples include death, initial or prolonged inpatient hospitalization, a life-threatening experience, persistent or significant disability or incapacity, and congenital anomaly.

An event is treatment-emergent if it occurs between the dose and up to 52 weeks afterward and was absent before treatment or worsened relative to the participant’s pretreatment state. This definition sets a time window and distinguishes new or worsened events from conditions already present before dosing. Counting participants with events is a binary-outcome approach at the participant level: each participant is classified according to whether the endpoint occurred, rather than counting every event as a separate participant.

Safety endpoints are used to describe the occurrence of unwanted events during treatment and follow-up. Such counts can help characterize observed safety experience, but a count alone does not establish whether an event was caused by the study drug. The registry’s endpoint definition explicitly does not require a causal relationship. The record does not report a comparative primary-endpoint analysis or an endpoint result for the full stated safety population.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What is the endpoint type? The primary endpoint counts participants with at least one treatment-emergent adverse event or serious adverse event. In general, this is a binary participant-level outcome: a participant either meets the endpoint definition or does not. The endpoint’s count is useful for describing how many participants experienced an event, but a comparison between groups also depends on the number of participants assessed in each group and on how missing observations are handled. The registry record does not report a primary-endpoint analysis or its analysis method.

What can randomization contribute?

In general, random assignment is used to reduce systematic differences between treatment groups at the start of a study. It does not guarantee that groups will be identical, particularly in a study with a limited number of participants, and it cannot resolve differences in follow-up or outcome recording after assignment. The record identifies the study as randomized but does not report the randomization sequence, allocation concealment, stratification, or the actual randomized counts by group. No more detailed account of the procedure is reported in the registry record.

What does double masking mean?

In general, masking aims to limit the influence of knowledge about assigned treatment on participants’ reporting, clinical care, and outcome assessment. The registry labels the study double-blind, but does not say which roles were masked, how the blind was maintained, or whether any unmasking occurred. Therefore the label describes the stated design, not evidence about how masking operated in practice.

How should the adverse-event counts be read?

Counts of participants with events are descriptive. A count without a corresponding analysis does not provide an estimate of the difference between groups or the precision of that difference. In general, a confidence interval expresses the range of values compatible with the observed data under a specified statistical method and assumptions. A wider interval indicates greater uncertainty; an interval’s interpretation depends on the quantity being estimated and the method used. No confidence interval for the primary endpoint is reported in the registry record.

Likewise, a p-value is a measure derived from a statistical test under a specified null model; it is not a measure of clinical importance or the probability that a treatment works. The registry record reports no primary-endpoint p-value and does not state a test for the endpoint. No particular testing method, adjustment, or model should be inferred from the design description alone.

What is the role of the pharmacokinetic outcomes?

The secondary outcomes name maximum observed serum concentration, time to maximum observed concentration, areas under the concentration curve, systemic clearance, volume of distribution at steady state, mean residence time, and serum decay half-life. In general, these measures describe different features of drug concentration over time and drug disposition. For example, a maximum concentration describes a peak observed level, while an area under a concentration curve summarizes concentration across a time interval. These concepts do not supply results: the registry record does not report numerical pharmacokinetic estimates, their dispersion, or comparisons among doses.

What does the sample-size illustration mean?

Any sample-size illustration associated with these data is described as planning based on an observed effect, not as the trial’s original design justification. Its stated assumptions are a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation; the target effect is a stated fraction of the observed effect. Such calculations are planning illustrations, not observed power and not evidence that the study had a particular probability of detecting an effect. The registry record does not report a sample-size justification for the original trial, and no illustration values are reported in the registry record.

In general, a planning calculation depends on the outcome, effect size, variability or event rate, significance criterion, allocation, and chosen method. Changing those assumptions can change the projected sample size. An illustration derived from an observed effect is especially dependent on the estimate used and should not be treated as a prospective design decision. The registry record does not describe an original power calculation or explain a planned detectable difference.

What analysis methods are not documented?

The registry record does not report a statistical analysis plan for the primary endpoint, a model, a hypothesis test, a confidence-interval method, a missing-data method, or an interim-analysis plan. It also does not describe how repeated assessments, if any, were handled. These omissions do not show that such methods were never planned or used; they mean the methods are not reported in the registry record. The posted counts can be read descriptively, but they cannot support reconstruction of an unreported analysis.

10. Multiplicity, Missing Data and Analysis Populations

The study lists a primary safety endpoint and multiple secondary pharmacokinetic outcomes. Testing or estimating many outcomes can raise multiplicity concerns: in general, the more statistical claims considered, the more important it is to distinguish prespecified primary questions from exploratory findings and to describe any adjustment strategy. The registry record does not report a multiplicity plan, a hierarchy for secondary outcomes, or any adjustment method. It reports 0 analyses, so there are no listed primary or secondary analysis results from which to assess how multiple comparisons were handled.

Missing-data handling is also not reported in the registry record. The record defines the safety population as all randomized participants who received at least 1 dose, but does not give the number with endpoint data, losses to follow-up, reasons for missing assessments, or an approach to participants with incomplete follow-up. In general, the consequences of missingness depend on how much information is absent and why it is absent. A count among observed participants may not fully describe the intended population if follow-up is incomplete.

The record does not specify an intention-to-treat analysis, a per-protocol analysis, or another named analysis population for the primary endpoint. The safety-population definition is the only population description stated for safety data. It should not be assumed that the primary endpoint used a particular denominator beyond the information explicitly recorded. Nor should the registered enrollment of 80 be taken as the analyzed sample size for any outcome. More complete participant flow and analysis-population details are not reported in the registry record.

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 0% reporting threshold.

Most frequent non-serious adverse event terms

The posted adverse-event group information reports no serious adverse events among 6 participants in each listed bapineuzumab group: 0.15 mg/kg, 0.5 mg/kg, 1.0 mg/kg, and 2.0 mg/kg. It reports no serious adverse events among 8 placebo participants. For other adverse events, the respective counts are 5 among 6, 3 among 6, 6 among 6, and 3 among 6 in those dose groups, and 7 among 8 for placebo. Death counts are not reported in the registry record.

These counts describe the listed groups and should not be read as a causal comparison. The registry does not report an inferential analysis, confidence intervals, or a complete account of the participants contributing to each endpoint. The serious-event counts do not establish that serious risk was absent; they describe the observed count in the listed groups. The record also does not provide serious-event terms, as the list of top serious terms is empty. The 2.0 mg/kg group appears in the adverse-event information but not in the arm descriptions, and the registry record does not explain this discrepancy.

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

The record identifies a randomized, double-blind, placebo-controlled Phase 1 study focused on safety, tolerability, and pharmacokinetics after single ascending doses of bapineuzumab. It gives a primary safety endpoint and descriptive adverse-event counts for several groups. These details establish what the study set out to assess and provide a limited account of observed events in the listed groups.

The record does not report a primary-endpoint comparison, a confidence interval, a p-value, or an analysis population count by arm. It therefore does not quantify the precision of any group difference or support a conclusion that one dose had more or fewer events than placebo. The posted counts should be read as descriptive observations, not as proof of a treatment effect or absence of an effect. Because the endpoint includes events regardless of causal relationship, an event recorded after treatment is not necessarily caused by treatment.

The stated pharmacokinetic outcomes also describe what was assessed, not the findings. Numerical concentration, exposure, clearance, distribution, residence-time, and half-life results are not reported in the registry record. Likewise, the record does not explain the relationship between the listed 2.0 mg/kg adverse-event group and the arm descriptions, which list other doses.

Overall, the registry information is insufficient to reconstruct the trial’s statistical conclusions. The absence of a reported analysis should not be interpreted as a null result, and the event counts should not be generalized beyond the populations and groups described. A fuller interpretation would require outcome results, denominators, participant flow, and analysis methods, which are not reported in the registry record.

13. Why This Trial Matters Statistically

This trial is statistically notable for combining a randomized, double-blind, placebo-controlled design with a Phase 1 focus on safety and pharmacokinetics. The stated primary endpoint is a participant count over follow-up up to Week 52, while secondary outcomes cover several distinct features of bapineuzumab’s serum concentration and disposition. The design and endpoint definitions show why the evidence needs to be read as safety and pharmacokinetic assessment rather than assumed to be an efficacy comparison.

The registry information also illustrates a common distinction between a study’s stated purpose and the results available for statistical interpretation. A trial can register outcome definitions and group descriptions without posting an inferential analysis. In this record, the primary analysis count is 0, and there is no primary-endpoint effect estimate or uncertainty interval. Descriptive counts alone cannot show how precise a dose-placebo difference might be.

Another statistical issue is alignment between the groups described in different parts of a record. The arm descriptions list three bapineuzumab dose levels, while the adverse-event groups include an additional 2.0 mg/kg group. Without an explanation, this makes it difficult to understand the complete set of treatment groups from the registry record. Participant counts and analysis populations also matter: enrollment is not the same as the number included in a particular outcome analysis, and the record does not provide that full accounting.

The study therefore provides a useful example of how endpoint definitions, analysis reporting, and consistency of group descriptions affect interpretation. Its registry record supports a cautious description of the study and its listed safety counts, but not a reconstructed treatment comparison or a conclusion about pharmacokinetic findings.

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 principal limitation for interpretation is that the registry record does not report a primary-endpoint analysis, an effect estimate, a confidence interval, or a p-value. It gives no numerical pharmacokinetic results despite listing multiple pharmacokinetic outcomes. This prevents assessment of the magnitude and precision of any between-group differences and limits evaluation of the study’s stated objectives.

The adverse-event groups include a 2.0 mg/kg bapineuzumab group, whereas the arm descriptions list 0.15 mg/kg, 0.5 mg/kg, and 1.0 mg/kg or placebo. The record does not explain whether the listed group reflects a different description, an additional group, or another issue. No explanation should be assumed. The adverse-event counts also do not supply full participant flow, randomized counts by arm, or an account of the number assessed through follow-up.

Although the registry gives a safety-population definition, it does not report missing-data handling or the analysis population used for each endpoint. It does not describe the statistical analysis plan, multiplicity strategy, interim analyses, or original sample-size justification. The listed enrollment of 80 cannot be treated as the number analyzed for a particular outcome. The registry record also does not report death counts, and it supplies no serious-event terms in the listed top-term field.

These limitations concern what is documented in the registry record. They do not establish that additional analyses, methods, or results did not exist; those details are not reported in the registry record. The posted group counts should therefore be interpreted narrowly as descriptive information.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: Study Evaluating Single Ascending Doses of AAB-001 Vaccine SAD Japanese Patients With Alzheimers Disease — NCT00397891.
• Registry record last updated 2014-09-04; status last verified 2014-08.
• Results first posted 2014-09-04.
• 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.

18. Record Summary

NCT00397891 is a completed Phase 1 randomized, double-blind, placebo-controlled, parallel-group study of single ascending doses of AAB-001, identified as bapineuzumab, in Japanese patients with mild to moderate Alzheimer’s disease. The registry lists enrollment of 80, a start of 2006-10, and primary completion of 2010-02.

The primary endpoint counts participants with treatment-emergent adverse events or serious adverse events from baseline up to Week 52. The record also lists pharmacokinetic secondary outcomes. Descriptive serious and other adverse-event counts are available for the listed groups, including a 2.0 mg/kg group not included in the arm descriptions. No primary-endpoint analysis or numerical pharmacokinetic results are reported in the registry record.