Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp (NCT02838628), a non-randomized phase 2 study. The primary outcome is Percentage of Participants With Complete Response of Actinic Keratosis.

2. Clinical Question

The study was intended to evaluate activity, safety, and pharmacokinetics of KX2-391 ointment in this population. The registry record describes two treatment schedules, but the non-randomized allocation means that a difference between their observed outcomes would not, by itself, establish that treatment duration caused the difference. Participant characteristics, clinical circumstances, or other factors could differ between the groups. The central statistical question is therefore descriptive: what complete-response percentage was observed in the defined evaluable population, and how uncertain was that estimate? Because the registry record does not report the endpoint result, those quantities cannot be assessed from the record.

3. Trial Design

This was a Phase 2a, open-label, multicenter study with a parallel model and non-randomized allocation. The registry record lists enrollment of 168 participants and a completed status. The stated study dates are 2016-04-11 for study start and 2017-01-11 for primary completion. Participants had actinic keratosis on the face or scalp and received KX2-391 Ointment 1% according to one of two schedules.

In the 5-day schedule, participants applied 50 mg topically once daily for 5 consecutive days to a 25 cm² treatment area. In the 3-day schedule, participants applied 50 mg topically once daily for 3 consecutive days to a 25 cm² treatment area. Both schedules used the same ointment and stated application area. The registry record does not describe a randomized allocation process, and its own warning says that the arms are not a like-for-like control comparison. The study is therefore not a randomized test of the schedules.

Open-label means that treatment assignment was not masked, while non-randomized means assignment was not made through random allocation. In general, these design features can leave outcome assessment open to expectations and can permit differences between groups apart from the assigned schedule. The record does not provide further information on how participants entered each schedule or whether outcome assessments were independently masked.

The primary endpoint was the percentage of participants with complete response at Day 57. The evaluable set included protocol-eligible participants who received the 5-day schedule in Cohort 1 or the 3-day schedule in Cohort 2 and completed both Day 1 and Day 57 lesion evaluations. The registry record does not report the number in this evaluable set or the observed primary response results. Although secondary outcomes include partial response, lesion-count change, and safety measures, their numerical results are also not reported in the registry record.

The registry record does not report the protocol’s statistical plan, the rationale for the enrollment target, or the procedure used to allocate participants. Those details should not be inferred from the listed design features or enrollment count.

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: A total of 168 participants (84 each cohort) were enrolled and treated in this study. This study consisted of 2 periods, first was Treatment and Follow-up period (up to Day 57) and second was Recurrence follow-up period (12 months post-Day 57).

Treatment and Follow-up Period

Recurrence Follow-up Period

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Evaluable set included group of protocol-eligible participants who received 5 days (Cohort 1) or 3 days (Cohort 2) of study treatment and completed Day 1 and Day 57 AK lesion evaluations.

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 analysis set included all participants who received at least one dose of study treatment.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Participants With Complete Response of Actinic Keratosis, measured over Day 57.

The primary endpoint is the percentage of participants with complete response of actinic keratosis at Day 57. Complete response was defined as 100% clearance in the treatment area on the face or scalp. The specified population is the evaluable set: protocol-eligible participants who received the assigned schedule and completed lesion evaluations at Day 1 and Day 57.

A percentage expresses the share of the analyzed participants who met the endpoint definition. It is useful for describing how often a prespecified clinical response was observed in the target treatment area. The Day 57 assessment gives a fixed time point for applying the definition, rather than combining observations from different follow-up times. In general, a confidence interval around a percentage conveys the uncertainty associated with estimating the underlying response rate from the observed participants.

The registry record identifies a 95% confidence interval as the endpoint’s dispersion measure, but it does not report the response percentage or the confidence-interval limits. The record also does not state how many participants were included in the evaluable set. Consequently, the size and precision of the observed response estimate cannot be described from the registry record.

This endpoint concerns complete clearance within the specified treatment area at the specified assessment time. It does not, by itself, describe response outside that area or establish a comparative effect between schedules. Because allocation was non-randomized and there was no like-for-like control comparison, any schedule contrast would require cautious interpretation even if the numerical results were available.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

The methods information in the registry record supports a description of the endpoint and study structure, but not a reconstruction of the full statistical analysis. The primary endpoint is a percentage, with a 95% confidence interval specified as the dispersion measure. The record does not report the numerical estimate, interval limits, or the statistical method used to calculate the interval. The trial’s full statistical plan is not reported in the registry record.

What does a percentage endpoint represent?

A percentage for a binary endpoint represents the proportion of analyzed participants who meet a defined condition. Here, the condition is complete response: 100% clearance in the face or scalp treatment area at Day 57. Each participant is classified according to whether the endpoint definition was met. In general, the percentage is a compact description of the observed response frequency, but it depends on the population included in the calculation and on consistent application of the endpoint definition.

The population matters because the primary endpoint is not defined over every enrolled participant. The registry record defines an evaluable set consisting of protocol-eligible participants who received the 5-day or 3-day schedule and completed the Day 1 and Day 57 lesion evaluations. The size of this set is not reported in the registry record. Without that denominator and the number meeting the response definition, the percentage cannot be independently understood or checked.

How should a confidence interval be understood?

In general, a confidence interval expresses statistical uncertainty around an estimate. For a response percentage, it indicates a range of values compatible with the observed data under the interval method and its assumptions. A narrower interval generally indicates greater precision, while a wider interval indicates less precision. The interval does not replace the point estimate, and it does not remove limitations arising from study design, endpoint measurement, or missing outcome data. The registry record specifies a 95% confidence interval for the primary endpoint, but its limits are not reported in the registry record; consequently, no conclusion about the interval’s width or the estimate’s precision is possible.

What does the allocation imply for a schedule contrast?

The parallel model describes groups followed under different schedules. In this study, one group received 50 mg of KX2-391 Ointment 1% once daily for 5 consecutive days and the other received the same stated amount once daily for 3 consecutive days. The allocation was non-randomized and the study was open-label. In general, random allocation helps balance measured and unmeasured participant characteristics across groups, while masking can reduce some risks of expectation influencing assessment. Neither feature is present as described in the registry record. A numerical difference between the schedules, if reported, would therefore be an observed contrast rather than an unambiguous causal effect of treatment duration.

The registry record itself warns that the arms are not a like-for-like control comparison. This matters because the groups do not provide an untreated or placebo reference, and allocation was not randomized. Comparing their percentages would not, on its own, establish what would have happened to similar participants under the alternative schedule. The record does not describe adjustment methods that might address measured differences, and no such methods should be assumed.

What do the safety summaries describe?

The registry record reports counts of participants with serious adverse events and counts with other adverse events for each schedule, along with deaths and selected serious-event terms. These summaries can describe what was recorded among participants at risk in each group. In general, a participant count is not necessarily the same as an event count: an individual can experience more than one event, while a participant-level summary may count that individual once for a stated category. The record’s adverse-event figures should be interpreted according to the labels and denominators reported, without assuming that the events were caused by the study treatment.

For safety comparisons, group size, follow-up, event definitions, and ascertainment procedures all affect interpretation. The registry record includes 84 participants at risk for each listed schedule in the safety summaries, but does not provide enough detail to determine whether exposure or observation time was equivalent. The serious-event terms are listed with percentages, but the record does not identify an arm for each term in that listing. They should not be assigned to a particular schedule without an explicit attribution.

What can planning illustrations establish?

The registry record describes planning illustrations based on the observed effect, with a two-sided significance level of 0.05, equal allocation between the two arms, and a normal approximation. It says that the effect to detect is a stated fraction of the observed effect, and that non-time-to-event illustrations give participants per arm. These are planning assumptions, not observed trial outcomes. The numerical illustrations themselves are not reported in the registry record, and the assumptions do not establish the study’s original design rationale. The record does not report the trial’s own sample-size justification. Such planning quantities must not be interpreted as observed power or as evidence that an endpoint result was precise.

Overall, the statistical information permits a clear account of what the primary endpoint was intended to measure and what the specified analysis population required. It does not permit reconstruction of the endpoint estimate, confidence interval, analysis method, or adjusted treatment contrast. Those items 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("KX2-391 50 mg (Days 1 to 5)", "KX2-391 50 mg (Days 1 to 3)")
n      <- c(84, 84)
events <- c(36, 27)
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  KX2-391 50 mg (Days 1 to 5)  84  36  42.9  32.1  54.1  32.8  53.5  32.8  53.6
ARM  KX2-391 50 mg (Days 1 to 3)  84  27  32.1  22.4  43.2  23.1  42.7  23.1  42.8

11. Multiplicity, Missing Data and Analysis Populations

The registry record lists 14 outcome measures and identifies a primary endpoint, with secondary outcomes covering partial response, lesion-count change at several visits, adverse events, local skin reactions, laboratory findings, vital signs, and electrocardiograms. Considering multiple outcomes or multiple assessment times raises a general statistical issue: the more hypotheses examined, the greater the chance that at least one result may appear notable by chance if no adjustment or prespecified testing strategy is used. Whether that issue was addressed in this study is not reported in the registry record.

The record reports 0 analyses. Numerical results for the primary endpoint and listed secondary outcomes are not reported in the registry record. It also does not report a multiplicity adjustment, a hierarchy for testing endpoints, or which outcomes were intended to support formal hypothesis tests. It is therefore not possible to determine whether any reported endpoint-level inference was adjusted for the number of outcomes examined.

The primary endpoint population is described as an evaluable set requiring protocol eligibility, treatment receipt, and completed Day 1 and Day 57 lesion evaluations. The count in that set is not reported in the registry record. The record does not describe how missing lesion assessments were handled, whether participants with incomplete evaluations were excluded, or whether any imputation or sensitivity analyses were used. Those missing-data procedures are not reported in the registry record and should not be inferred from the evaluable-set definition.

In general, exclusions from an analysis population can affect how representative the result is of all enrolled participants, especially if completion of follow-up is related to response or tolerability. This is a methodological consideration rather than a finding about this study: the registry record does not state why any participant may have failed to complete an evaluation. The distinction between enrollment and the endpoint analysis population remains important when interpreting the intended response percentage.

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 0% reporting threshold.

Most frequent serious adverse event terms

Most frequent non-serious adverse event terms

Serious events with the highest arm-level rate: benign prostatic hyperplasia (2.4%), arteriosclerosis coronary artery (1.2%), small intestinal obstruction (1.2%), appendicitis (1.2%), cerebrovascular accident (1.2%).

The registry record reports 84 participants at risk in each schedule for the serious adverse event and other adverse event summaries. In the 5-day schedule, 4 participants were reported with a serious adverse event and 37 with other adverse events; deaths were 0. In the 3-day schedule, 3 participants were reported with a serious adverse event and 19 with other adverse events; deaths were 0. These are participant counts as presented in the record, not a causal assessment.

Serious adverse events and other adverse events are separate categories in the reported summaries. The serious-event figures should not be combined with the other adverse event figures, and the record does not establish that every event was related to KX2-391. The percentages listed for selected serious-event terms are Benign Prostatic Hyperplasia, 2.4%; Arteriosclerosis Coronary Artery, 1.2%; Small Intestinal Obstruction, 1.2%; Appendicitis, 1.2%; Cerebrovascular Accident, 1.2%; and VIIth Nerve Paralysis, 1.2%. The registry record does not assign those listed terms to a specific schedule in that listing.

In general, safety counts describe events recorded during the study; interpretation also depends on definitions, observation periods, and ascertainment. The registry record does not provide further detail on those points. The counts therefore describe what is listed, but cannot establish comparative risk or causation.

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

The registry record establishes that this was an open-label, non-randomized Phase 2a study of KX2-391 Ointment 1% in adults with actinic keratosis on the face or scalp. It describes two treatment schedules and defines complete response at Day 57 as 100% clearance in the treatment area. It also specifies that the primary endpoint was intended to be reported as a percentage with a 95% confidence interval.

Those design and endpoint details do not reveal the primary result. The response percentage, confidence-interval limits, and evaluable-set size are not reported in the registry record. Therefore, the record does not show how often complete response occurred or how precisely that rate was estimated. It also does not support a numerical statement about the difference between schedules.

Even if a difference between schedules were available, the non-randomized allocation and absence of a like-for-like control comparison would constrain causal interpretation. Both groups received KX2-391 ointment, but treatment duration differed. Without randomization, outcome differences could reflect factors other than schedule. The open-label design is another relevant feature when considering assessment and reporting, although the registry record does not describe whether any particular assessment was masked.

The safety summaries report serious adverse events, other adverse events, and deaths by schedule, together with selected serious-event terms. They are descriptive counts and do not, on their own, establish that treatment caused an event or that one schedule is safer than the other. The registry record does not provide additional information about exposure time or event attribution that would support a stronger comparison.

In general, a registry entry can describe a study’s design, planned or defined outcomes, and posted results. Here, the design and endpoint definitions are available, but numerical results for the activity outcomes are not reported in the registry record. The appropriate interpretation is consequently limited: the study’s question and measurement framework can be described, while the primary activity result and its precision cannot be assessed from the record.

14. Why This Trial Matters Statistically

This trial is statistically informative in part because its design makes the distinction between description and causal comparison important. The registry record presents two schedules of the same ointment, with different treatment durations, but allocation was non-randomized. The study’s arms therefore do not function as randomized treatment and control groups. Any contrast between them would need to be interpreted as an observed group difference, not automatically as the effect of changing treatment duration.

The primary endpoint is also clearly defined: complete response at Day 57 required 100% clearance in the treatment area. A prespecified, concrete definition helps clarify what the response measure is intended to capture. At the same time, the endpoint’s analysis population is evaluable rather than simply all enrolled participants. That distinction highlights why the denominator and handling of incomplete evaluations matter when interpreting a response percentage. The evaluable-set size and missing-data procedures are not reported in the registry record.

The record further illustrates that an endpoint definition is not a result. It specifies a 95% confidence interval as the dispersion measure, but does not report the primary percentage or interval limits. Readers therefore cannot judge the observed response or its statistical precision. The registry record lists 14 outcome measures but reports 0 analyses, leaving the numerical activity findings and any approach to multiple outcomes unreported.

Finally, the safety summaries show why event counts should be kept in context. Participant counts can describe events recorded in each schedule, but they do not establish treatment causality or a comparative safety effect. The registry record supplies design and selected safety details, yet important elements for statistical interpretation—including the primary result, analysis methods, and missing-data approach—are not reported in the registry record. That boundary between what is described and what can be inferred is central to reading the study responsibly.

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 principal limitation for interpreting activity is that numerical primary and secondary outcome results are not reported in the registry record. Although complete response is defined and a 95% confidence interval is specified, the response estimate and its interval limits are absent. The record also does not report the number of participants in the evaluable set, so the primary endpoint denominator cannot be assessed.

The study was non-randomized and open-label, and the registry record explicitly cautions that the schedules are not a like-for-like control comparison. Both groups received KX2-391 Ointment 1%, differing in the number of consecutive treatment days. This design limits the interpretation of any group contrast as a causal effect of schedule. The record does not report methods for adjustment for differences between groups.

The endpoint analysis population required participants to be protocol-eligible, to have received treatment, and to complete Day 1 and Day 57 lesion evaluations. The record does not report how many enrolled participants met these criteria or how incomplete evaluations were handled. Missing-data methods, sensitivity analyses, and reasons for non-completion are not reported in the registry record.

The registry record lists 14 outcome measures but reports 0 analyses. A statistical testing strategy, any multiplicity procedure, and the full analysis plan are not reported. The study’s sample-size justification is also not reported in the registry record; planning assumptions based on an observed effect do not substitute for that justification. For safety, selected event counts and terms are listed, but the record does not provide further detail on event attribution or whether observation and exposure periods were comparable between schedules. These limitations define what can be concluded from the registry record, without establishing that any specific bias or problem occurred.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: Activity & Safety Study of KX2-391 Ointment in Participants With Actinic Keratosis on the Face or Scalp — NCT02838628.
• Registry record last updated 2021-04-14; status last verified 2021-03.
• Results first posted 2021-04-14.
• 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

NCT02838628 is a completed Phase 2a, open-label, multicenter, non-randomized study of KX2-391 Ointment 1% in adults with actinic keratosis on the face or scalp. The registry record lists enrollment of 168 participants. One schedule applied 50 mg once daily for 5 consecutive days; the other applied 50 mg once daily for 3 consecutive days, both to a 25 cm² treatment area.

The primary endpoint was the percentage of evaluable participants with complete response at Day 57, defined as 100% clearance in the treatment area. The endpoint result, confidence-interval limits, and evaluable-set size are not reported in the registry record. The record lists safety counts for serious and other adverse events, as well as 0 deaths in each schedule. Because allocation was non-randomized, the groups are not a like-for-like control comparison, and numerical outcome results are not reported in the registry record, the activity findings cannot be quantified from this record.