A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor (NCT01974206), a randomized phase 2 study. The primary outcome is Percentage of Participants With CMV Viremia Through 1 Year Post First Study Drug Injection.

2. Clinical Question

3. Trial Design

This was a Phase 2, randomized, parallel-group, double-blind, placebo-controlled trial of ASP0113 in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. The registry lists quadruple masking. Enrollment was 150. The study status is completed; its recorded start date was 2013-11-20 and its primary completion date was 2016-05-13.

The intervention schedule was tied to transplant timing. The transplant was designated Day 0, and five injections were scheduled on days 30, 60, 90, 120 and 180. ASP0113 was administered as 1 mL of 5 mg/mL in the deltoid muscle, alternating sides at successive doses. Placebo was administered in the same volume, concentration description, location and schedule. The record does not report the allocation ratio or the number randomized to each group for the primary endpoint analysis.

The stated purpose was to evaluate ASP0113 compared with placebo for reducing CMV viremia incidence, while also evaluating safety in this population. The primary outcome was the percentage of participants with viremia through one year after the first study-drug injection. Secondary outcomes listed in the record included adjudicated CMV-associated disease, plasma viral load at or above the lower limit of quantification, adjudicated CMV-specific antiviral therapy, and graft survival during the primary study period or long-term follow-up.

The registry record does not report the detailed statistical analysis plan, the rationale for the planned enrollment, or whether interim analyses were conducted. The primary endpoint results are not reported in a form that permits a single comparison between treatment groups. Consequently, the trial’s design can be described, but its primary treatment-effect estimate cannot be interpreted from the posted results.

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: Screening assessments were performed from 14-30 days after the transplant. Participants were randomized at day 30 in relation to the day of the transplant, in a 1:1 ratio to ASP0113 or placebo. Participants were stratified by the use of antithymocyte globulin (ATG) prior to randomization and by the receipt of a kidney from a living or deceased donor.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: The Full Analysis Set (FAS) consisted of all randomized patients who received at least 1 dose of randomized study drug and who had at least 1 post dose viral load assessment within 1 year post first injection by central laboratory.

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: Randomized population: Age, Gender, Race, Ethnicity Randomized population: Use of ATG, Source of current Transplant, randomization strata

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With CMV Viremia Through 1 Year Post First Study Drug Injection, measured over From first study dose injection (day 1) up to one year post study drug injection (up to Day 380).

The primary endpoint was the percentage of participants with CMV viremia through one year after the first study-drug injection. The registry defines viremia as the presence of cytomegalovirus measured by central laboratory plasma viral load of at least 1000 IU/mL. Viral-load measurements after the first injection through Day 380, whether scheduled or unscheduled, were included. A participant with more than one qualifying viral-load result was counted once.

This endpoint represents whether a participant met the specified virologic threshold during the stated follow-up period, rather than the number of positive tests or the duration of viremia. The use of a central laboratory assay provides a common measurement source for the endpoint. A binary participant-level outcome can make the proportion of participants meeting a defined threshold straightforward to compare between groups, provided the analysis results and methods are available.

The registry also specifies that a participant who discontinued the study without a positive CMV viral load was imputed as having CMV viremia. This rule affects how the endpoint is classified when follow-up ends without a positive result. The record does not provide the endpoint counts, percentages, treatment-effect estimate or uncertainty interval for the primary comparison. It therefore does not establish how often viremia occurred in either group or how precisely any difference was estimated.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Several statistical ideas help explain what the registry record can and cannot support. The distinctions below are general statistical explanations; they do not describe analyses unless those analyses are explicitly reported in the record.

What does a percentage endpoint represent?

The primary endpoint classifies each participant according to whether CMV viremia occurred during the specified follow-up window. A participant with one or more qualifying central-laboratory results is counted once. The endpoint is therefore a participant-level event indicator, summarized as a percentage. Such an outcome is different from a repeated-measures summary of every viral-load test: multiple positive tests for one participant do not create multiple endpoint events under the registry definition.

For a comparison between randomized groups, the group percentages would describe the observed frequency of the endpoint. A treatment-effect estimate would then express the contrast using a specified measure, such as a difference or ratio, and a confidence interval could indicate the precision of that estimate. A confidence interval gives a range of values compatible with the data and the method’s assumptions; it is not a guarantee that the true effect lies within that range. The registry record does not report the primary group percentages, effect estimate or confidence interval, so none can be interpreted.

Why does endpoint definition matter?

A threshold-based endpoint depends on the threshold and measurement process. Here, the registry defines viremia using central-laboratory plasma viral load of at least 1000 IU/mL. A value below that threshold does not meet the stated primary definition, even though a different secondary outcome concerns plasma viral load at or above the lower limit of quantification. Those endpoints answer different questions: one applies the specified viremia threshold, while the other is defined in relation to the assay’s lower limit of quantification.

Follow-up also shapes interpretation. The primary endpoint covers the interval from the first study-drug injection through one year after that injection, with viral loads through Day 380 included. A result summarizes endpoint occurrence over that defined period, not an unrestricted claim about later outcomes. The record does not report the primary comparison or additional details on the timing of endpoint events.

How should the imputation rule be understood?

The registry says a participant who discontinued without a positive CMV viral load was imputed as having viremia. Imputation is a rule for assigning an analysis value when the observed information does not establish the outcome in the usual way. This particular rule treats that specified discontinuation pattern as an endpoint event. It can therefore influence the estimated percentage, especially if discontinuation differs between groups. The record does not report how many participants were classified this way or whether other missing-data situations occurred.

In general, missing-data assumptions matter because the unobserved outcome is not directly known. An analysis may make assumptions about what would have happened after missing follow-up, and different assumptions can yield different estimates. The stated discontinuation rule is one element of the analysis definition; it is not enough to reconstruct all missing-data handling. The registry record does not report sensitivity analyses or the full statistical plan.

What is the role of the analysis population?

The primary analysis population was the Full Analysis Set. It included randomized participants who received at least one dose and had at least one post-dose viral-load assessment within one year after the first injection by central laboratory. This definition excludes some randomized participants if they did not meet the stated treatment and assessment conditions. Randomization is intended to support a fair comparison between groups, while restrictions after randomization can affect how closely the analyzed groups preserve that balance. The record does not provide the number analyzed in each group or a separate analysis of all randomized participants.

Analysis populations answer different questions. An analysis restricted by treatment receipt and available assessment may not be identical to an analysis retaining every randomized participant. Without the population counts and results, the consequences of the Full Analysis Set definition cannot be quantified for this trial. The record also does not report whether additional populations were used for safety or secondary endpoints beyond the safety counts presented.

What can a significance test tell a reader?

In general, a p-value measures how unusual data at least as incompatible with a specified null hypothesis would be, if that hypothesis and the test assumptions held. It does not measure the probability that the null hypothesis is true, and it does not describe the size or clinical importance of an effect. A small p-value does not replace an effect estimate and its uncertainty; a larger p-value does not prove equivalence or absence of an effect.

No primary p-value or inferential test is reported in the registry record. The stated sample-size illustration assumptions include a two-sided significance level of 0.05, equal allocation and a normal approximation. These are assumptions for a planning illustration, not evidence that the trial’s own design used them. The record does not report the trial’s sample-size justification or a primary analysis test.

How should planning illustrations be read?

Sample-size calculations are planning tools that relate an assumed effect, variability, significance threshold and desired power to a required number of participants. A calculation based on an observed effect is a retrospective planning illustration, not a description of the effect the trial was designed to detect. If the assumed effect is changed to a stated fraction of the observed effect, the calculation asks how enrollment needs would change under that assumption; it does not create a new observed result.

Such illustrations are not observed power. Observed power calculated from a trial’s estimated effect largely restates information in the result and does not resolve uncertainty. Planning values also depend on assumptions that may not match the trial’s actual design. The record does not report the trial’s own sample-size justification. Because the primary outcome has several categories or time points and is not reduced to one comparison, a single primary-effect planning comparison is not available from the posted information.

Why might over-dispersion matter?

Over-dispersion is a general statistical issue in count data: the observed variation can exceed what a simple model assumes. When it is present, standard errors from an overly restrictive model may be too small, making confidence intervals too narrow and tests too optimistic. The primary endpoint in this trial is described as a participant percentage, not a count of repeated events; participants with multiple qualifying viral loads were counted once. The registry record does not report an over-dispersion assessment or a model-based primary analysis, so this general consideration should not be mistaken for a method used in the trial.

In sum, statistical interpretation requires the endpoint definition, analysis population, missing-data rules, group results and uncertainty estimates. The registry provides some definitions and safety counts, but the primary comparison and detailed inferential methods are not reported in the registry record.

10. Multiplicity, Missing Data and Analysis Populations

Multiplicity arises when a study makes several statistical comparisons or evaluates several outcomes. If each is tested independently at a conventional threshold, the chance of at least one false-positive result can increase. Statistical plans often address this through a prespecified testing order, adjustment procedure, or clear designation of which outcomes are confirmatory and which are exploratory. These are general principles; the registry record does not report a multiplicity strategy for this trial.

The record identifies one primary outcome and lists secondary outcomes covering adjudicated CMV-associated disease, plasma viral load at or above the lower limit of quantification, adjudicated CMV-specific antiviral therapy, and graft survival at different follow-up periods. Listing multiple outcomes does not show that all were tested inferentially, nor does it establish how any tests were ordered or adjusted. The detailed statistical plan and any interim analyses are not reported in the registry record.

Missing information also affects interpretation. The primary analysis population required randomization, at least one dose, and at least one post-dose central-laboratory viral-load assessment within one year. The endpoint definition further classifies a participant who discontinued without a positive viral load as having viremia. The record does not provide the number of participants affected by this rule, the amount of missing data, reasons for discontinuation, or sensitivity analyses under alternative assumptions.

Safety counts use reported at-risk and affected totals, but the record does not describe the detailed safety analysis procedures or how missing safety follow-up was handled. Taken together, these gaps prevent assessment of the full multiplicity and missing-data strategy. They also make it important not to infer a primary treatment effect from the outcome list or the descriptive safety figures.

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.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: renal failure acute (13.3%), cytomegalovirus infection (9.3%), cytomegalovirus syndrome (6.8%), cytomegalovirus viraemia (6.7%), escherichia urinary tract infection (6.7%).

The registry reports serious adverse event counts for 74 participants at risk in the placebo group and 75 in the ASP0113 group. Serious adverse events affected 36 participants in the placebo group and 44 in the ASP0113 group. For other adverse events, 72 of 74 participants at risk in the placebo group and 75 of 75 in the ASP0113 group were affected. Deaths were recorded for 5 participants in the placebo group and 7 in the ASP0113 group.

These figures are counts of participants, not a complete description of event frequency over time. A participant may have experienced more than one event, and the registry record does not provide event-level timing or duration in these entries. The listed serious-event terms and percentages include renal failure acute at 13.3%, cytomegalovirus infection at 9.3%, cytomegalovirus syndrome at 6.8%, cytomegalovirus viraemia at 6.7%, Escherichia urinary tract infection at 6.7%, and blood creatinine increased at 6.7%.

The record does not provide enough context to assign those listed percentages to a particular group or to compare them as treatment effects. Descriptive safety counts alone do not establish causation. Interpretation would require fuller details about event definitions, follow-up, severity, relatedness, and the handling of repeat events. These figures should be read as registry-reported safety observations, not as a stand-alone estimate of comparative risk.

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

The trial addresses a defined clinical research question: whether ASP0113, compared with placebo, changed the percentage of CMV-seronegative kidney transplant recipients with CMV viremia during the specified follow-up period after receiving a kidney from a CMV-seropositive donor. The record gives the endpoint threshold, follow-up window, dosing schedule, and analysis-population definition. These details clarify what the study intended to measure.

However, the primary group results and comparative estimate are not reported in the registry record. It is therefore not possible to describe the observed direction, size or precision of the primary treatment effect. The study purpose does not establish the result, and completion of the trial does not reveal whether the primary endpoint differed between groups. No conclusion about whether the intervention increased, decreased or left viremia unchanged can be drawn from the posted primary outcome information.

The safety counts provide descriptive information for the groups, including serious adverse events, other adverse events and deaths. They are relevant observations, but without further analysis details they do not establish that ASP0113 caused the events or that the groups had a statistically reliable difference. The listed serious-event terms also do not, on their own, resolve comparative safety.

The record names secondary outcomes, but their presence does not fill the gap in the primary comparison. The trial’s findings should not be generalized beyond the specified study population and outcome definitions without additional evidence. Nor does the available record establish long-term effects simply because graft survival during long-term follow-up appears among the secondary outcomes.

In short, the registry record documents the question, design and some safety counts, but it does not supply the primary results necessary to quantify the trial’s answer. That distinction separates what the study set out to investigate from what can be concluded from the posted data.

13. Why This Trial Matters Statistically

This trial is statistically notable for the way it defines a participant-level virologic endpoint in a transplant population. The outcome is not a count of every positive test: a participant with more than one qualifying central-laboratory viral-load result is counted once. That distinction affects both the interpretation of the endpoint and the type of analysis needed to compare groups.

The endpoint also includes an explicit rule for a particular missing-follow-up situation. Participants who discontinued without a positive viral load were classified as having viremia. This makes the handling of discontinuation part of the outcome definition rather than a detail that can be ignored. The rule is transparent in the record, but its impact cannot be assessed without knowing how many participants it affected and the group-specific results.

The randomized, masked, placebo-controlled design is relevant because those features are intended to support a fair comparison. The record also reports a clearly specified dosing schedule and a Full Analysis Set definition. Yet a design description alone cannot establish an intervention effect. The absence of the primary comparison means readers cannot assess the estimated effect or its precision, even though the intended outcome and analysis population are described.

The safety information illustrates another statistical distinction: counts of affected participants are descriptive, while conclusions about comparative risk require appropriate context and analysis. The serious-event terms and overall counts are useful to recognize as reported observations, but the record does not provide enough detail to interpret them as causal or conclusive group differences.

For these reasons, the trial is useful as an example of why endpoint definitions, missing-data rules and analysis populations matter, and why reported design features cannot substitute for results. The statistical account remains incomplete without the primary group outcomes and uncertainty estimates.

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 main trial-specific limitation in the registry record is that the primary outcome is not reported as a single comparison between ASP0113 and placebo. The record describes a percentage endpoint with several categories or time points, and the primary result is not reduced to one comparison. Group-specific primary counts, percentages, an effect estimate and an uncertainty interval are not reported. The primary treatment effect therefore cannot be quantified or interpreted.

The record defines the Full Analysis Set but does not report how many participants in each group met that definition. The total enrollment is 150, while the safety at-risk counts are 74 for placebo and 75 for ASP0113; the record does not establish that those safety denominators are the primary analysis denominators. No primary outcome counts should be inferred from them.

The endpoint definition includes imputation of viremia for participants who discontinued without a positive viral load, but the record does not state how many participants were classified this way. It also does not report the reasons for discontinuation, the extent of missing viral-load data, or sensitivity analyses. These omissions limit assessment of how the rule affected the primary result.

The registry record does not report the detailed statistical analysis plan, the trial’s sample-size justification, interim analyses, or the method for handling multiplicity across primary and secondary outcomes. The listed serious adverse event percentages are not accompanied by enough detail in the record to establish their group attribution or support a comparative analysis. These limitations constrain both efficacy interpretation and a full statistical assessment of safety.

15. Related Tutorials

16. Related Statistical Calculators

17. Sources

• ClinicalTrials.gov: A Study to Evaluate the Efficacy and Safety of a Vaccine, ASP0113, in Cytomegalovirus (CMV)-Seronegative Kidney Transplant Recipients Receiving an Organ From a CMV-Seropositive Donor — NCT01974206.
• Registry record last updated 2024-10-24; status last verified 2024-10.
• Results first posted 2022-01-04.
• 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

NCT01974206 was a completed, randomized, parallel-group, quadruple-masked, placebo-controlled Phase 2 trial with enrollment of 150. It evaluated ASP0113 in CMV-seronegative kidney transplant recipients receiving a kidney from a CMV-seropositive donor. Study start was recorded as 2013-11-20 and primary completion as 2016-05-13.

ASP0113 and placebo were scheduled as deltoid injections on days 30, 60, 90, 120 and 180 in relation to transplant Day 0. The primary outcome was the percentage of participants with CMV viremia through one year after the first study-drug injection, using a central-laboratory threshold of at least 1000 IU/mL.

The registry record reports safety counts, but does not report a single primary outcome comparison or the detailed statistical plan. As a result, the primary treatment effect and its precision cannot be established from the posted results.