An Open-Label Safety Study of A-101 Solution: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for An Open-Label Safety Study of A-101 Solution (NCT02667288), a na phase 3 study. The primary outcome is Proportion of Subjects With Lesion Clearance.

2. Clinical Question

The study description says the investigator would identify 4 eligible SK target lesions on each subject on the trunk, extremities and face. The endpoint therefore concerns clearance across a subject’s target lesions, not the clearance of an individual lesion considered separately. A subject is counted as meeting the endpoint only when all target lesions satisfy the clear assessment described in the record.

This is a safety-focused question in an open-label study, alongside a lesion-clearance measure. Without a control group, the design can describe outcomes observed among participants who received A-101 Solution, but it cannot directly estimate a difference relative to untreated participants or another intervention. The registry record does not report a comparative efficacy question or an adjusted treatment-effect analysis.

3. Trial Design

NCT02667288 is titled “An Open-Label Safety Study of A-101 Solution.” Its official title describes an open-label study of the safety of A-101 Solution 40% in subjects with seborrheic keratosis on the trunk, extremities and face. The registry lists the phase as PHASE3, the status as COMPLETED, and enrollment as 147.

The design is classified as SINGLE GROUP, with allocation listed as NA and masking as NONE. The intervention is A-101 Solution, described as administered once. The registry does not list a placebo, active comparator, or separate control arm. Consequently, the study is not a randomized comparison, and outcomes in the treatment group cannot be contrasted with outcomes in a like-for-like control group within this record.

The brief description states that investigators would identify 4 eligible SK target lesions on each subject on the trunk, extremities and face. The primary outcome is assessed at study day 148. The record also lists Per Subject Percent of Lesion Clearance as a secondary outcome. It identifies 2 outcome measures, while the analysis count is 0.

The recorded start is 2016-01 and primary completion is 2016-10. The sponsor is Aclaris Therapeutics, Inc. The registry does not report further details about the visit schedule, the procedures used to administer the solution beyond the once-only description, or the rationale for the enrollment target. Those details should not be inferred from the design labels or from the listed dates.

Because the study is open-label, participants and investigators were not masked according to the registry entry. This matters especially for an assessment involving investigator judgment: awareness of treatment can be a potential source of assessment bias. The record identifies the Physician Lesion Assessment scale but does not report whether additional safeguards were used to reduce that risk.

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: ITT Population

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: ITT Population

6. Primary Endpoint

The registry lists the primary outcome as Proportion of Subjects With Lesion Clearance, measured over Study day 148.

The primary endpoint is titled “Proportion of Subjects With Lesion Clearance.” Its unit is participants, and its description defines a subject as meeting the endpoint when all target lesions are judged clear on the Physician Lesion Assessment (PWA) Scale at study day 148. The scale is described as a 4 point scale used by the investigator to assess each subject’s target SK lesion.

This endpoint translates lesion assessments into a participant-level outcome. Rather than treating each lesion as an independent participant, it asks whether the full set of target lesions for a subject meets the clearance criterion. That can make the endpoint relevant to the overall target-lesion status for each participant, but it also means that a participant does not meet the endpoint if any target lesion fails the specified clear assessment. The record does not supply the scale’s individual response categories or further rules for handling assessments.

A binary participant outcome can be reported as a count or a proportion, making it straightforward to describe how many participants met the defined criterion. Such a measure is useful when the clinical question is whether all selected lesions reached a stated assessment category by a particular time. It does not, by itself, describe degrees of improvement among participants who did not meet the all-lesions-clear rule.

The record names the ITT Population for this endpoint, but the outcome result itself is not reported in the registry record. Therefore, no observed clearance count, proportion, or precision estimate can be stated from the listed information.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The registry labels the primary outcome as a participant count and describes the endpoint as the proportion of subjects for whom all target lesions were judged clear. This is a binary outcome at the participant level: each participant either meets the stated rule or does not. The lesion assessments are the basis for that participant-level classification. The registry does not report the outcome count or proportion, so there is no observed estimate to interpret or independently recalculate.

What does a confidence interval describe?

In general, a confidence interval expresses the uncertainty around an estimated quantity under a statistical model and its assumptions. For a participant-level proportion, the interval would indicate a range of values compatible with the observed data under the chosen method. It is not a guarantee that the true value lies in that range, nor does it correct bias caused by study design, outcome measurement, missing data, or selective reporting. No confidence interval for the primary endpoint is reported in the registry record.

What does the single-group design allow?

The study is listed as SINGLE GROUP, with allocation NA and masking NONE. In a single-group study, a proportion can describe the participants observed, but there is no concurrent control proportion for estimating a between-group contrast. A one-group estimate answers a descriptive question about the recorded cohort; a comparative effect requires a suitable comparison and assumptions that support the contrast. As no comparator is listed, a treatment difference, relative effect, or comparative risk cannot be inferred from this record.

General causal interpretation also depends on how participants entered the study, how outcomes were measured, and how missing observations were handled. A registry design label alone does not establish that these issues were resolved. The record does not report the recruitment details, endpoint adjudication procedures, or missing-data strategy.

Why does open-label assessment matter?

The primary outcome depends on an investigator’s assessment using the PWA Scale. The record describes it as a 4 point scale but does not give the category labels or additional scoring instructions. In general, use of a defined scale can make an assessment more structured, but judgment-based measures may still be affected by expectations or differences in how assessors apply criteria. Open-label status means masking is not listed; the record does not report whether standardized training, independent review, or other assessment safeguards were used.

How should the planning assumptions be read?

The registry includes assumptions for planning illustrations: a two-sided significance level of 0.05, equal allocation between two arms, a normal approximation, and an effect defined as a stated fraction of the observed effect. The assumptions also distinguish illustrations for time-to-event outcomes from those for other outcomes. These are planning conventions, not evidence that the trial itself used a two-arm randomized design. The actual study is classified as single-group, and allocation is listed as NA.

In general, sample-size calculations estimate how much information a future study might need to detect an effect under specified assumptions. Their outputs depend on the assumed effect, variability, allocation, significance threshold, and analysis method. A planning calculation is not observed power and does not indicate the probability that the observed result is true. Here, the registry record does not report the primary outcome estimate or numerical sample-size illustration results, so the planning assumptions cannot be translated into a trial-specific numerical conclusion.

A normal approximation is a general method for simplifying the distribution of an estimator when its conditions are appropriate. Whether it is suitable depends on the data structure and the size and pattern of the observed information. For a binary outcome, the count of participants meeting the criterion and the total assessed population would be relevant to evaluating precision. Those primary outcome counts are not reported in the registry record.

Over-dispersion is a general concern when data vary more than a statistical model expects. It can arise when observations are clustered or more heterogeneous than assumed, and ignoring it may make uncertainty appear too small. The primary endpoint is defined at the participant level, while lesion assessments contribute to that classification. The record does not describe a model that accounts for lesion-level clustering, nor does it report a dispersion estimate. This point is a general methodological consideration, not a claim that over-dispersion was present or that a particular adjustment was required.

The registry’s analysis count is 0. That entry does not supply a test method, model specification, confidence interval procedure, covariate adjustment, or sensitivity analysis. Such methods should not be imputed from the endpoint type or from general conventions. The sponsor’s analysis results, if any, are not reported in the registry record.

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("A-101 Solution")
n      <- c(147)
events <- c(16)
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  A-101 Solution  147  16  10.9  6.4  17.1  6.8  16.9  6.8  17.0

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies the primary outcome and lists Per Subject Percent of Lesion Clearance as a secondary outcome. It reports 2 outcome measures and 0 analyses. It does not report a multiplicity plan, such as a prespecified hierarchy among outcomes or an adjustment to account for testing more than one outcome. Without that information, the record does not show how any formal statistical claims across outcomes would have been controlled. No such claims can be reconstructed from the outcome titles alone.

Missing-data handling is also not reported in the registry record. The primary endpoint is assigned to the ITT Population, but the record does not define how participants with unavailable or incomplete lesion assessments were treated in the analysis. In general, excluding participants with missing outcomes, treating them as not meeting the endpoint, or using a model-based approach can lead to different estimates and relies on different assumptions. None of those approaches should be attributed to this study without documentation.

The record does not describe a per-protocol population, a safety population definition beyond the adverse-event denominators, or sensitivity analyses for incomplete data. It therefore is not possible to assess whether the reported adverse-event counts and the intended ITT endpoint population used the same inclusion rules. This uncertainty is about reporting, not evidence that data were missing or that a particular analysis was performed.

For interpretation, the stated endpoint, population label, and event counts can be reported as written, while the unreported analysis choices remain unresolved. A more complete statistical account would require details on missing assessments, analysis populations, multiplicity handling, and the methods used to estimate uncertainty.

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 1% reporting threshold.

Most frequent non-serious adverse event terms

The adverse-event summary lists 147 participants at risk for serious adverse events and 0 affected. For other adverse events, it lists 147 at risk and 14 affected. These are the counts recorded for the A-101 Solution group. The registry does not list serious adverse event terms in its serious-event summary.

These figures describe what the record reports; they do not establish that the intervention caused or prevented an event. In an uncontrolled study, there is no comparison group to distinguish events occurring during the study from events that might also occur in a similar group under different conditions. The figures also do not convey event severity beyond the serious-versus-other categories shown, timing, duration, recurrence, or individual clinical context.

The serious-event figure should be read as a recorded count, not as proof that serious events are impossible or that none occurred outside the registry’s reporting scope. Likewise, the other-event count does not show how many events occurred, since the summary counts affected participants. The record does not report further detail about event types, attribution, or analysis methods. These limitations do not alter the listed counts, but they restrict the conclusions that can be drawn from them.

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

The record documents a completed PHASE3, open-label, single-group safety study of A-101 Solution 40% in subjects with seborrheic keratosis. It specifies a once-only administration, a primary endpoint based on all target lesions being judged clear at study day 148, and an ITT Population for that endpoint. It also records safety counts for serious and other adverse events. These elements describe what the registry entry says the study involved and what results it lists.

The primary clearance result is not reported in the registry record. Consequently, the record does not establish the observed proportion of subjects meeting the endpoint, the precision of that estimate, or the degree of lesion clearance among those who did not meet the all-lesions-clear criterion. The secondary outcome is named, but its result is not reported either.

The design also does not support a controlled comparison. Without a listed comparator, the study cannot estimate how outcomes differed from an untreated group or another intervention within this record. Open-label investigator assessment may be relevant to interpreting a judgment-based endpoint, while the registry does not report assessment safeguards that would clarify this issue.

The adverse-event counts are descriptive. They do not by themselves identify cause, establish comparative safety, or provide detail about the specific events beyond the categories and counts listed. The recorded zero serious adverse events should not be taken as proof that serious harms cannot occur; it is the count in this registry summary.

Thus, the documented information is useful for understanding the study’s structure and the definitions and counts it records. It does not establish a comparative treatment effect, a precise lesion-clearance estimate, or a complete safety profile. Those conclusions would require outcome results and methodological details that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial is statistically informative as an example of how design and endpoint definitions shape the claims a study can support. The registry’s single-group classification makes the distinction between descriptive outcomes and comparative effects especially important. A participant-level clearance proportion, if reported, would describe the cohort under observation; it would not by itself identify the effect attributable to treatment.

The primary outcome also illustrates how a lesion-level assessment can be converted into a participant-level endpoint. Requiring all target lesions to be judged clear creates a clear decision rule for classifying participants, but it does not show the distribution of partial or incomplete clearance unless those details are reported separately. The record names a secondary measure of per-subject percent lesion clearance, but it does not report its result.

Assessment methods matter because the endpoint relies on investigator judgment and the study is open-label. Statistical interpretation is not limited to the choice of a test: it also depends on measurement quality, transparency about missing data, and the way uncertainty is reported. These methodological details are not available in the registry record.

Finally, the entry shows why outcome definitions and outcome results must be distinguished. A detailed endpoint description tells readers what was intended to be measured; it is not a substitute for the observed count, estimate, and uncertainty. The listed safety counts similarly describe recorded events without providing a controlled safety comparison. The record therefore supports careful description, while leaving key questions about the magnitude, precision, and comparative meaning of outcomes unanswered.

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.

Several limitations arise from the information recorded for this specific study. The registry identifies a single-group, open-label design, with no comparator listed and allocation recorded as NA. This prevents a like-for-like controlled comparison in the registry entry. Any outcome description would therefore need to remain distinct from a causal or comparative estimate.

The primary endpoint depends on investigator judgment using the PWA Scale. Although the scale is described as a 4 point scale, the record does not list its category labels, detailed assessment rules, or any independent review procedure. Since masking is listed as none, the possibility of assessment bias is relevant, but whether safeguards were used is not reported.

Most importantly, the registry record does not report the primary clearance result or the secondary outcome result. It therefore does not provide the outcome counts needed to assess the observed clearance proportion or its statistical precision. The analysis count is 0, and the record does not provide a statistical analysis plan, confidence intervals, inferential tests, or model details.

The handling of missing assessments, analysis populations beyond the named ITT Population, and multiplicity is not reported in the registry record. The adverse-event summary supplies counts but not event terms for serious events, attribution, timing, or further clinical detail. These gaps limit interpretation of both efficacy-related outcomes and safety reporting.

Finally, the planning assumptions described for sample-size illustrations are not the design of this single-group study. Their two-arm allocation premise should not be mistaken for trial conduct, and no numerical illustration results are available in the registry record. The record does not report the sample-size justification for enrollment or whether interim analyses were conducted.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: An Open-Label Safety Study of A-101 Solution — NCT02667288.
• Registry record last updated 2018-02-07; status last verified 2016-12.
• Results first posted 2017-11-17.
• 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

NCT02667288 is a completed PHASE3, open-label, single-group safety study of A-101 Solution 40% in subjects with seborrheic keratosis on the trunk, extremities and face. Enrollment is listed as 147. The intervention is described as administered once, with masking NONE and allocation NA.

The primary endpoint is the proportion of subjects whose target lesions were all judged clear on the Physician Lesion Assessment Scale at study day 148, in the ITT Population. Per Subject Percent of Lesion Clearance is listed as a secondary outcome. The primary and secondary outcome results are not reported in the registry record, which lists 0 analyses.

The safety summary lists 0 serious adverse events among 147 at risk and 14 participants with other adverse events among 147 at risk. No serious adverse event terms are listed. These counts are descriptive and do not provide a controlled comparison or establish causation.