Open-label Study of ASP2151 in Herpes Simplex Patients: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Open-label Study of ASP2151 in Herpes Simplex Patients (NCT02209324), a na phase 3 study. The primary outcome is Percentage of Participants With Healing by Day 8.

2. Clinical Question

The clinical question in the registry is whether participants treated with ASP2151 achieved lesion healing by Day 8 of study treatment. The study included patients with herpes simplex, with the description referring to recurrent labial or facial herpes, recurrent genital herpes, and Kaposi varicelliform. The primary endpoint is framed as the percentage of participants with healing by the stated time point.

This is a single-group study, not a randomized comparison. It therefore describes outcomes among participants who received ASP2151, rather than estimating a treatment contrast against a concurrent control group. Without a control group, the endpoint cannot by itself distinguish the effect of treatment from other influences on healing, such as the course of the condition over time or differences among participants.

The registry identifies the efficacy analysis set as patients diagnosed with labial or facial herpes or recurrent genital herpes at case registration, who subsequently received the study drug at least once and had an efficacy variable measured. It also mentions excluding patients found not to have herpes simplex after, but the exclusion statement is incomplete in the registry record. The exact full population definition is therefore not reported in the registry record.

The record does not report how many participants in the efficacy analysis set had healed by Day 8, the corresponding percentage, or an uncertainty interval. It also does not report a statistical analysis for this endpoint. The clinical question is identifiable, but the posted registry information does not provide the result needed to assess the observed rate of healing or its precision.

3. Trial Design

This was a Phase 3, multicenter, open-label study of ASP2151 in patients with herpes simplex. The registry lists the study as completed and records an enrollment of 275. It gives a start date of 2013-11 and a primary completion date of 2015-07. These registry fields describe the study record; they do not establish the number of participants who received treatment or contributed data to each analysis.

The design is recorded as single group, with no masking and allocation listed as not applicable. ASP2151 is the only intervention and arm named in the record. There is no concurrent control arm described. This structure supports description of outcomes observed among people treated in the study, but it does not supply a randomized between-group comparison. In particular, a result from this design should not be read as a direct estimate of how outcomes would differ under another treatment or no treatment.

The study summary says it evaluated efficacy and safety in patients with recurrent labial or facial herpes, recurrent genital herpes, and Kaposi varicelliform. The listed secondary outcomes are time to healing, time to complete crusting, and time to virus disappearance. The record lists four outcome measures in total, including the primary endpoint, but it does not provide analysis entries.

The registry record does not report the treatment regimen, study-drug dose, treatment duration, eligibility criteria in full, or a detailed protocol for assessments. It also does not report a protocol-specific statistical analysis plan or sample-size justification. These omissions limit assessment of how the study was conducted and how the planned analyses were intended to address the clinical question.

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: Efficacy analysis set was defined as patients who were diagnosed with labial/facial herpes or recurrent genital herpes at the time of case registration, subsequently received the study drug at least once, and had any efficacy variable measured, except for those found not to have herpes simplex after study drug administration.

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: Efficacy analysis set was defined as patients who were diagnosed with labial/facial herpes or recurrent genital herpes at the time of case registration, subsequently received the study drug at least once, and had any efficacy variable measured, except for those found not to have herpes simplex after study drug administration.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Healing by Day 8, measured over 8 days.

The primary endpoint is the percentage of participants with healing by Day 8 of study treatment. It measures whether a participant's lesion had reached the registry's healing outcome by the specified assessment time. The endpoint is binary at the participant level: a participant either meets the healing criterion by that time or does not. The registry describes the outcome as a count of participants and gives a timeframe of 8 days.

A fixed-time binary endpoint can be useful because it gives a clinically interpretable summary at a defined point in treatment. It differs from a time-to-event measure: it does not, by itself, describe when healing occurred before Day 8, and it does not distinguish participants who heal soon after treatment begins from those who heal later but still by the assessment time. The listed secondary outcome, time to healing, addresses a different aspect of the healing process.

The relevant denominator is the efficacy analysis set, described in the registry as patients diagnosed with labial or facial herpes or recurrent genital herpes at case registration, who received study drug at least once and had an efficacy variable measured, with an exclusion statement that is incomplete. The registry does not report the number in this endpoint's analysis set or the number who achieved healing by Day 8. Consequently, the percentage and its precision are not reported in the registry record.

The endpoint definition is stated, but details of the clinical criteria for healing, assessment procedures, and handling of missing Day 8 assessments are not reported in the registry record. Those details matter for interpreting how consistently the outcome was measured.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

Interpreting an endpoint begins with identifying what is counted, when it is assessed, and which participants are eligible for the analysis. In this study, the primary outcome is a participant count for healing by Day 8, expressed as a percentage. The registry calls the measure the percentage of participants with healing by Day 8 and defines the timeframe as 8 days. The population description refers to an efficacy analysis set, but the complete definition is not available in the registry record.

What does a percentage estimate?

In general, a percentage for a binary endpoint is the number of participants meeting the outcome divided by the number of participants assessed in the relevant analysis population. It describes the observed frequency in that population. Its interpretation depends on the outcome definition, the population included, and how missing assessments are handled. Here, the record does not report the endpoint numerator or denominator, so the percentage cannot be reconstructed or checked from the registry information.

A confidence interval, in general, expresses uncertainty around an estimated quantity. For a participant-level binary endpoint, an interval around a percentage would help show how much precision the observed rate has, taking account of the number of participants contributing data. The registry does not report an interval for healing by Day 8. Without the estimate and its interval, neither the outcome level nor its precision can be evaluated from the posted results.

What does the single-group design allow?

In general, an uncontrolled study can estimate or describe outcomes among participants receiving the study intervention, provided the outcome data and analysis are reported. A randomized control group serves a different purpose: it offers a contemporaneous reference and supports estimation of a between-group contrast. Because this study is recorded as single group, with allocation not applicable and no masking, it does not yield a randomized treatment contrast. Any observed outcome would need to be interpreted as an outcome in the study group, rather than as a controlled estimate of treatment effect.

Open-label status means the study is not recorded as masked. In general, knowledge of treatment assignment can influence aspects of assessment or reporting, especially when an endpoint requires judgment. The registry does not report the criteria used to determine healing, whether outcome assessors were independent, or the procedures used to reduce assessment bias. These details would help readers judge how the endpoint was measured.

Why do analysis populations matter?

The registry describes an efficacy analysis set based on diagnosis, receipt of study drug at least once, and measurement of an efficacy variable. It also contains an incomplete exclusion phrase relating to patients subsequently found not to have herpes simplex. In general, an analysis population definition determines which participants contribute to an estimate and can affect how broadly the result applies. Because the full definition and the actual endpoint denominator are not reported, the analysis population cannot be fully assessed.

Missing outcome data can also affect a binary endpoint. In general, participants without an observed Day 8 assessment may be excluded, treated under a specified missing-data rule, or addressed through sensitivity analyses. These choices can lead to different estimates and should be prespecified and explained. The registry does not report the number with missing Day 8 data or the method used to handle it.

What can be inferred from the planning illustrations?

The statistical planning illustrations are explicitly described as based on an observed effect and as separate from the trial's own design. Their stated assumptions include a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is described as a fraction of the observed effect. Those assumptions concern a hypothetical planning exercise, not the actual single-group design recorded for this study.

In general, a planning calculation asks how much information a future study might require to detect a specified effect under stated assumptions. It is not an observed treatment effect, a result of the trial, or evidence that the trial had a particular probability of detecting an effect. Sample-size illustrations should not be described as observed power. The registry does not report the trial's own sample-size justification or a protocol-specific statistical plan, so the rationale for the enrollment figure cannot be evaluated from this record.

Finally, the record lists no analysis entries. This means that the registry information does not show the statistical procedures used for the primary or secondary outcomes. The choice of estimator, uncertainty interval, hypothesis test, covariate adjustment, or any sensitivity analysis is not reported in the registry record. General statistical principles can clarify what such methods would mean, but they cannot establish which methods were actually used in this study.

10. Exact Estimates for Each Arm

No two-arm comparison is shown for this trial, but each arm's result can still be summarized with exact interval estimates computed from the posted counts. The Clopper-Pearson interval is exact and conservative; the Wilson interval is a common closer-to-nominal alternative; the Bayesian credible interval uses a uniform Beta(1, 1) prior. For small groups the three can differ noticeably.

R code and output

arm    <- c("ASP2151")
n      <- c(265)
events <- c(194)
for (i in seq_along(n)) {
  ci <- binom.test(events[i], n[i])$conf.int          # Clopper-Pearson exact interval
  cr <- qbeta(c(0.025, 0.975), 1 + events[i], 1 + n[i] - events[i])   # Bayesian, uniform Beta(1,1) prior
  wi <- (function(x, n) { p <- x / n; z <- qnorm(0.975); d <- 1 + z^2 / n
    c((p + z^2 / (2 * n) - z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d, (p + z^2 / (2 * n) + z * sqrt(p * (1 - p) / n + z^2 / (4 * n^2))) / d) })(events[i], n[i])
  cat(sprintf("ARM|%s|%d|%d|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f|%.1f\n", arm[i], n[i], events[i], 100 * events[i] / n[i],
              100 * ci[1], 100 * ci[2], 100 * wi[1], 100 * wi[2], 100 * cr[1], 100 * cr[2]))
}

ARM  ASP2151  265  194  73.2  67.4  78.4  67.6  78.2  67.6  78.2

11. Multiplicity, Missing Data and Analysis Populations

The registry lists a primary outcome and three secondary outcomes: time to healing, time to complete crusting, and time to virus disappearance. Considering several outcomes can raise a multiplicity issue. In general, when multiple hypotheses are tested, the chance of at least one apparently notable result can increase unless the analysis plan accounts for the set of tests. The registry record does not report whether any adjustment, testing hierarchy, or other multiplicity strategy was planned or used. It also does not report analyses for these outcomes.

The primary endpoint's efficacy population is described, but the definition is incomplete at the point where the record refers to participants found not to have herpes simplex after. The size of that analysis set is not reported. The registry does not state how many participants had a Day 8 assessment, how many lacked one, or how missing efficacy data were handled. These omissions prevent assessment of the endpoint denominator and of potential bias from incomplete outcome measurement.

The record also does not report whether the listed outcomes were all prespecified in a protocol, whether additional outcomes were collected, or whether any analyses were changed after data review. Interim analyses and a detailed statistical analysis plan are not reported in the registry record. No assumptions about those procedures can therefore be made.

These reporting gaps matter because analysis populations, missing-data rules, and multiplicity procedures influence how results should be interpreted. In their absence, the registry's endpoint descriptions identify what was intended to be measured, but not how the full set of outcomes was statistically evaluated.

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 2% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: cellulitis of male external genitalorgan (0.4%), cervical dysplasia (0.4%).

The adverse-event record lists 271 participants at risk for serious adverse events and 2 participants affected. It separately lists 271 at risk for other adverse events and 53 affected. The record reports 0 deaths. These are counts, not comparative risk estimates, and the study has no control group for a like-for-like safety comparison.

The serious-event terms listed most often are cellulitis of male external genitalorgan and cervical dysplasia, each shown as 0.4%. The registry does not provide further detail about event timing, severity beyond the serious-event classification, recurrence, or whether investigators considered events related to ASP2151. The listed terms should therefore be read as registry-reported event descriptions, not as evidence of causation.

The enrollment field is 275, whereas the adverse-event record gives 271 at risk. These fields describe different aspects of the record, and the registry does not explain the difference. The enrollment figure should not replace the adverse-event denominator. The safety counts also do not indicate how events were distributed over time or whether all participants had the same duration of observation.

In general, safety counts describe what was recorded within the specified reporting categories. Without a control group and fuller event-level details, they cannot establish comparative safety or attribute an event to treatment. The registry does not report additional definitions or analysis methods for these safety summaries.

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

The record establishes that a completed, open-label, single-group Phase 3 study evaluated ASP2151 in patients with herpes simplex. It identifies healing by Day 8 as the primary endpoint and names secondary outcomes concerning healing, crusting, and virus disappearance. It also reports a limited set of adverse-event counts. These details clarify the study question and the type of evidence the design could generate.

The record does not report the primary endpoint result. There is no numerator, denominator, percentage, or confidence interval for healing by Day 8 in the registry information. Thus, it is not possible to determine the observed healing rate or how precisely it was estimated. The fact that the study is listed as completed does not itself supply an efficacy result.

Even if a healing percentage were available, a single-group result would describe outcomes among the treated study participants. It would not, on its own, quantify how outcomes compare with an alternative treatment or with no treatment. The open-label design also means masking was not used, while the registry does not give details about the healing criteria or assessment procedures. Those features would be relevant to interpreting any reported result.

The safety counts are similarly limited. They report participants affected in specified categories, but do not establish that ASP2151 caused the events or show how its safety compares with another option. Event definitions, attribution, and fuller follow-up details are not reported in the registry record.

The appropriate reading is therefore bounded: the registry documents a study design, an intended efficacy endpoint, and some safety counts, while leaving the main efficacy estimate and statistical analysis unreported. The record cannot support a numerical claim about the primary outcome or a controlled conclusion about treatment effects.

14. Why This Trial Matters Statistically

This study is statistically informative as an example of the distinction between a clearly named endpoint and a fully reported result. The registry specifies healing by Day 8 as the primary outcome and describes an efficacy analysis set. Those definitions help identify the intended estimand in broad terms: a participant-level healing frequency at a fixed time. But without the observed count, denominator, and uncertainty interval, the endpoint cannot be quantitatively interpreted.

The single-group design also illustrates why an outcome rate and a treatment effect are not interchangeable. A treated-group rate would describe what happened in the study group. A treatment effect in the comparative sense requires a suitable reference, and this record does not describe a concurrent control arm. Statistical language should preserve that distinction rather than turning an uncontrolled observation into a comparative claim.

The gap between the enrollment field and the adverse-event denominator highlights another general reporting issue: sample size depends on the analysis and outcome. Enrollment is not automatically the denominator for efficacy or safety. Clear reporting of each analysis population and its missing data is essential for readers to understand what a percentage represents.

Finally, the planning assumptions are not the study design. The registry describes sample-size illustrations using an equal-allocation, two-arm framework, while the actual trial is recorded as single group. The illustrations are planning exercises based on an observed effect, not observed power and not evidence that the study used that design. Keeping planning calculations separate from the trial's conduct and results is important for sound statistical interpretation.

15. Limitations

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

The main trial-specific limitation in the registry record is that the primary efficacy result is not reported. The endpoint is named, but there is no healing count, analysis denominator, percentage, or uncertainty interval. The registry also lists no analysis entries, leaving the statistical methods for the efficacy outcomes unreported.

The study has no randomized comparator. Its single-group, open-label design does not support a like-for-like comparison with another treatment, and the registry does not describe masking. The record also lacks the full clinical criteria for healing, the assessment process, and information on how Day 8 assessments were handled when missing.

The efficacy population definition is incomplete: the record describes diagnosis, treatment receipt, and measurement of an efficacy variable, then ends with an unfinished exclusion statement. It does not report the size of this population or how it relates to the enrollment field. The adverse-event risk set is reported separately, but the record does not explain the difference from the enrollment figure.

Further limitations include the absence of a reported statistical analysis plan, multiplicity procedures, missing-data methods, and detailed safety-event definitions or attribution. The registry also does not report the treatment regimen or full eligibility criteria. These omissions restrict assessment of reproducibility, risk of bias, and the applicability of any result. They should be understood as limits of the registry information, not proof that procedures or analyses were absent from the study itself.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Open-label Study of ASP2151 in Herpes Simplex Patients — NCT02209324.
• Registry record last updated 2024-09-27; status last verified 2024-02.
• Results first posted 2024-09-27.
• 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

The registry describes a completed, multicenter, open-label, single-group Phase 3 study of ASP2151 in patients with herpes simplex. Enrollment is listed as 275, with study dates of 2013-11 to 2015-07. The primary endpoint is the percentage of participants with healing by Day 8 of study treatment. Secondary outcomes concern time to healing, complete crusting, and virus disappearance.

The registry does not report the primary endpoint result, its analysis denominator, or a statistical analysis. The efficacy-population description is incomplete. Safety entries list 2 participants with serious adverse events among 271 at risk, 53 with other adverse events among 271 at risk, and 0 deaths; two serious-event terms are each listed at 0.4%. The single-group design does not provide a randomized comparison, and the registry record does not report enough detail to assess comparative efficacy or safety.