A Study of the KIO-201 (Ocular Bandage Gel) for Improving Persistent Corneal Epithelial Defects: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Study of the KIO-201 (Ocular Bandage Gel) for Improving Persistent Corneal Epithelial Defects (NCT05436288), a na phase 2 study. The primary outcome is Percentage of Patients Achieving Corneal Healing (<0.5 mm2 Lesion Size) of the Persistent Corneal Epithelial Defect at 4 Weeks.

2. Clinical Question

This question is exploratory. The study is a pilot, and the registry describes its primary effectiveness outcome as the percentage of patients achieving corneal healing. Its result characterizes the endpoint in the evaluable group; without a comparator, it cannot establish how that outcome would differ under another treatment or in the absence of KIO-201. The registry record does not report a prespecified comparative treatment effect or a formal hypothesis test.

3. Trial Design

The registry identifies this as a Phase 2 pilot study, with a single active arm and a single-group model. Allocation is listed as not applicable, and masking is listed as none. The study is marked completed. Enrollment is reported as 10. The registry gives a start date of 2022-07-01 and a primary completion date of 2022-12-22.

Participants in the active arm received topical KIO-201, a 0.75% crosslinked thiolated carboxymethyl hyaluronic acid gel, up to six times a day for 4 weeks. The brief summary describes administration six times per day while awake for 4 weeks. The registry does not report how actual use, adherence, dose interruptions, or deviations from the planned schedule were assessed.

The primary outcome was corneal healing by 4 weeks, defined as a lesion size below 0.5 mm2. The registry says assessment involved corneal fluorescein staining and photos. It also describes review by a reader using digital photography of fluorescein-stained slit-lamp photos and image analysis. The record does not report the reader's blinding status, the number of readers, or procedures for resolving disagreement.

This design can describe outcomes among participants who received the study gel and were evaluable. It does not provide a like-for-like control comparison: no control group is listed, and the study was not masked. Consequently, observed change or healing cannot be separated from other influences using a randomized between-group estimate. The registry record does not report a protocol-level account of the allocation rationale, sample-size justification, interim analyses, or detailed statistical analysis plan. The reported enrollment and completion status do not by themselves establish how many participants completed every study procedure.

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: Eight (8) eyes were evaluable Five (5) of 8 (62.5%) of the evaluable participants achieved the primary endpoint of healing (\<0.5 mm2 lesion size) at the 4-week period

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.

6. Primary Endpoint

The registry lists the primary outcome as Percentage of Patients Achieving Corneal Healing (<0.5 mm2 Lesion Size) of the Persistent Corneal Epithelial Defect at 4 Weeks, measured over 4 weeks.

The primary endpoint is the percentage of patients achieving corneal healing, defined in the registry as a persistent corneal epithelial defect lesion size below 0.5 mm2 at 4 weeks. The outcome is binary for each assessed participant: the endpoint is either met or not met according to that threshold. The reported result is five of 8 evaluable participants achieving healing. The record also says eight eyes were evaluable, so the distinction between eyes and participants should be kept in view when reading the description.

Corneal fluorescein staining and photographs were used to determine healing. The registry further describes evaluation by a reader using digital images of fluorescein-stained slit-lamp photographs and image analysis. A defined lesion-size threshold makes the outcome more explicit than a general description of improvement, while image-based assessment provides a documented approach to judging the endpoint. These features do not, by themselves, establish how consistently the threshold was applied or whether assessment was protected from bias; those procedures are not reported in the registry record.

A percentage endpoint is useful for describing how often a specified outcome occurred among those assessed. It does not convey the full range of lesion changes, and it does not show whether healing would be more or less frequent under a comparator. The registry record does not report a confidence interval for the result or a detailed account of how unevaluable cases were handled in the analysis.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a binary endpoint capture?

General statistical explanation: a binary endpoint classifies each assessed participant according to whether a specified condition is met. In this study, the condition is lesion size below 0.5 mm2 at 4 weeks. The registry's count of participants meeting that criterion is the central descriptive result. This format is straightforward to interpret, but it compresses information: it does not show how far a lesion was from the threshold, whether it changed substantially without crossing the threshold, or how outcomes varied among participants.

The percentage description expresses the count meeting the endpoint in relation to the evaluable group. Its interpretation depends on the denominator and the unit of analysis. Here, the registry says eight eyes were evaluable and reports five of 8 evaluable participants achieving the endpoint. That wording should be preserved rather than silently treating eyes and participants as interchangeable. The registry record does not provide enough detail to resolve the wording or describe the status of cases that were not evaluable.

What would an uncertainty estimate add?

General statistical explanation: a confidence interval gives a range of values compatible with the data under a specified statistical method and assumptions. It helps readers assess precision, which is distinct from whether an estimate is large or small. The registry record does not report a confidence interval for the healing result. It also does not report a p-value or a formal inferential analysis for the primary outcome. Thus, the record supports a descriptive account of the observed result, but not a registry-based statement about statistical significance or a precise range for the underlying healing rate.

Precision is particularly relevant when a result is based on a limited evaluable group. A single outcome can meaningfully affect the estimated proportion when the denominator is small. This is a general property of proportions, not an additional calculation for this study. Readers should avoid treating the reported percentage as if it were a stable population value or as if uncertainty had been quantified.

Why does the single-group design matter?

General statistical explanation: a control group can help distinguish outcomes associated with an intervention from outcomes that might also occur because of natural history, concurrent care, measurement processes, or other influences. A randomized comparison can reduce systematic differences between groups, while masking can help limit some forms of assessment or treatment-related bias. This study has a single active arm, allocation is listed as not applicable, and masking is listed as none. The registry therefore reports an outcome after exposure, not a randomized contrast.

Without a comparator, no between-group effect can be estimated from the described design. The result cannot show what would have happened to a comparable group without KIO-201 or under another intervention. The registry's image-based assessment is relevant to how the endpoint was evaluated, but the record does not say whether the reader was masked to treatment or provide other details that would establish protection against observer expectations.

What is over-dispersion, and does it apply?

General statistical explanation: over-dispersion is a concern for some count models when observed variability exceeds the variability assumed by the model. It can make standard errors too small if the model does not accommodate that extra variation. The primary outcome is a binary healing endpoint, not a rate of repeated events or a count outcome described with a dispersion parameter. The registry lists no dispersion value and no analysis model, so there is no basis to claim that over-dispersion was assessed or relevant to the sponsor's primary analysis.

How should planning calculations be understood?

General statistical explanation: sample-size calculations are planning tools that estimate the number of observations that might be needed under specified assumptions. They are not evidence that a study had a particular probability of detecting an effect after the data were collected. The planning illustration associated with this trial is described as based on the observed effect, using a two-sided significance level of 0.05, equal allocation between two arms, and a normal approximation. The effect to detect is expressed as a stated fraction of the observed effect. These are planning assumptions, not the trial's own documented design justification; the actual study was single-group.

Accordingly, any planning figures should not be interpreted as observed power or as evidence that the study was sized to test a randomized comparison. The registry record does not report the original sample-size justification or a prospective comparative design. The distinction matters because a calculation based on an observed pilot result is illustrative and may be sensitive to the uncertainty in that result. It cannot repair the absence of a comparator or establish the precision of the reported endpoint.

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("Single Arm Active")
n      <- c(8)
events <- c(5)
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  Single Arm Active  8  5  62.5  24.5  91.5  30.6  86.3  29.9  86.3

11. Multiplicity, Missing Data and Analysis Populations

The registry identifies one primary outcome measure: the percentage of patients achieving corneal healing at 4 weeks. It describes this as the primary exploratory effectiveness outcome. The record does not report a multiplicity adjustment, a hierarchy of outcomes, or a plan for controlling the chance of false-positive findings across multiple analyses. It also does not report interim analyses or the statistical plan for any secondary outcomes. The registry lists one outcome measure and no analysis results, so the available record does not permit a broader assessment of multiplicity procedures.

The registry reports five of 8 evaluable participants achieving the primary endpoint and says eight eyes were evaluable. Enrollment was 10. The record does not explain why not all enrolled participants or eyes appear in the evaluable description. It does not state whether these cases lacked follow-up, failed another evaluability criterion, withdrew, or had another status; none of those explanations should be inferred. The record does not report an imputation method, a missing-data assumption, a sensitivity analysis, or an intention-to-treat result.

These gaps matter because the interpretation of a percentage depends on which participants contribute to its denominator and how absent outcomes are handled. A complete-case result describes those with an evaluable endpoint; it does not automatically describe the full enrolled group. The registry's wording also shifts between eyes and participants, so the analysis unit is not fully clear from the outcome description alone. The record does not report whether the endpoint was analyzed at the eye level, participant level, or using a method accounting for more than one eye per participant. These details limit assessment of both the denominator and the uncertainty around the result.

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 non-serious adverse event terms

The registry lists zero participants with serious adverse events among 10 at risk and zero deaths among 10 at risk in the single active arm. It lists four participants with other adverse events among 10 at risk. These are safety counts reported for the study group; they are not a comparison against an untreated or active control group.

A zero serious-event count means that no serious adverse events are recorded for the reported group in this registry entry. It does not establish that the intervention has no serious risks. Safety counts from a pilot study have limited ability to characterize uncommon events, and the record does not report a comparator that would help put the counts in context. The absence of recorded deaths is likewise a descriptive finding, not a comparative estimate.

The record does not provide the terms of the four other adverse events, their severity, timing, duration, relationship to treatment, or whether participants experienced more than one event. It also does not list serious adverse-event terms. No further interpretation of event types or causality is supported by the registry record. The counts should therefore be read as a limited summary of recorded safety outcomes, not as a complete account of safety or a basis for treatment decisions.

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

The primary result records that five of 8 evaluable participants met the specified corneal-healing threshold at 4 weeks. The finding describes outcomes observed in the single active arm of a completed pilot study. It is useful as a report of what the registry records for the evaluable group, but it does not establish a treatment effect relative to another option.

The design has no comparator and no masking. Consequently, the result cannot separate the intervention's contribution from other influences on healing or assessment. It also cannot show whether a different treatment, usual care, or no study intervention would have produced a different outcome. No comparative estimate, confidence interval, or p-value for the primary result is reported in the registry record. The result's precision and statistical significance therefore cannot be judged from the record.

The endpoint is a threshold-based measure at a specified follow-up time. It does not describe the full pattern of lesion sizes or the degree of change for each participant. The registry does not report a baseline summary or participant-level results. It also does not explain the gap between enrollment and the evaluable outcome description or resolve the wording about eyes and participants. The result should not be generalized automatically beyond the evaluable participants described.

The safety figures record no serious adverse events and no deaths among 10 at risk, alongside four participants with other adverse events among 10 at risk. These counts provide limited descriptive information, without event terms or a control group. They do not establish comparative safety or rule out events not observed in this study.

Overall, the registry result is best treated as an exploratory pilot observation. It can inform questions for further study, but it does not establish that KIO-201 caused the recorded healing outcomes, determine how outcomes compare with another approach, or provide a definitive estimate of effectiveness or safety. Those conclusions would require evidence and analyses not reported in the registry record.

14. Why This Trial Matters Statistically

This trial raises several useful statistical issues for clinical researchers. First, an outcome proportion is only interpretable when its analysis unit and denominator are clear. The registry reports enrollment of 10, says eight eyes were evaluable, and describes five of 8 evaluable participants as achieving healing. That wording makes it important to distinguish participants from eyes and to know which observations contribute to the estimate. The record does not resolve those details.

Second, the result is descriptive because the study has a single active arm. A favorable or unfavorable observed outcome cannot be interpreted as a treatment contrast without a comparator. Randomization and masking address different sources of bias; neither is reported for this study. This illustrates why a result following treatment exposure is not, by itself, a causal estimate.

Third, the registry calls effectiveness exploratory and reports a threshold-based endpoint assessed from staining and photographs. Such endpoints can offer a clear criterion, but interpretation still depends on measurement procedures, reader practices, and handling of cases that cannot be evaluated. Those details are not fully reported. A threshold also leaves out information about the degree of change within each outcome category.

Finally, pilot findings are often useful for identifying design and measurement questions, but their uncertainty should not be overlooked. No confidence interval or inferential analysis for the primary outcome is reported. Any planning calculations based on the observed effect are illustrations, not observed power and not evidence of the trial's original sample-size justification. This record therefore illustrates the value of reporting the analysis population, missing-data handling, assessment procedures, and uncertainty alongside an outcome count.

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 trial-specific limitations affect interpretation. The study is a pilot with a single active group, no comparator, and no masking. It cannot estimate a between-group treatment effect, and the registry does not report a formal comparative analysis. The primary outcome is described as exploratory, which further supports treating the finding as preliminary rather than confirmatory.

The outcome population is not fully explained. Enrollment is 10, while the primary result refers to eight evaluable eyes and five of 8 evaluable participants. The registry does not explain why the outcome is not reported for the full enrollment, whether eyes or participants are the analysis unit, or how cases not represented in the result were handled. No missing-data method or sensitivity analysis is reported.

The registry describes fluorescein staining, slit-lamp photographs, digital image analysis, and a reader assessment, but it does not report reader masking, reproducibility procedures, or how disagreements were handled. It also does not report participant characteristics, baseline lesion-size summaries, individual outcomes, or a fuller description of follow-up. These omissions make it difficult to judge how representative the evaluable group was or how consistently the endpoint was assessed.

The registry record does not report a confidence interval, p-value, detailed statistical analysis plan, sample-size justification, or interim-analysis plan. Safety information is limited to aggregate counts; event terms for other adverse events and details about timing or treatment relationship are not reported. These gaps constrain assessment of precision, potential bias, and the completeness of safety reporting.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Study of the KIO-201 (Ocular Bandage Gel) for Improving Persistent Corneal Epithelial Defects — NCT05436288.
• Registry record last updated 2024-04-03; status last verified 2024-03.
• Results first posted 2024-04-03.
• 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

NCT05436288 is a completed Phase 2 pilot study of topical KIO-201 for persistent corneal epithelial defects. It used a single active group, with no masking and no comparator. The registry reports enrollment of 10 and administration of KIO-201 up to six times a day for 4 weeks.

The primary endpoint was corneal healing at 4 weeks, defined as lesion size below 0.5 mm2 and assessed using fluorescein staining and photographs. The registry says eight eyes were evaluable and reports five of 8 evaluable participants achieving healing. It lists zero serious adverse events and zero deaths among 10 at risk, and four participants with other adverse events among 10 at risk.

The outcome is exploratory and descriptive. The registry record does not report a comparative effect, confidence interval, p-value, missing-data analysis, or detailed statistical plan. Its wording does not clarify the evaluable analysis unit or explain why the primary result is available for fewer than the enrolled group.