This page provides an independent statistical analysis and educational interpretation of publicly reported results. ClinicalTrials.gov provides the official trial registry record. Numerical trial results on this page are restricted to the results posted in the ClinicalTrials.gov record; calculations added by Clinical Biostats are labelled as such.
1. Trial at a Glance
This page covers the registry results for Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects (NCT01165450), a randomized phase 2 study. The primary outcome is Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT01165450 |
| Phase | Phase 2 |
| Condition | Persistent Corneal Epithelial Defects |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Triple |
| Enrollment | 2 |
| Arms in the primary outcome | n/a |
| Lead sponsor | University of California, San Francisco |
| Results posted | Yes |
2. Clinical Question
Population
The study concerned subjects with persistent corneal epithelial defects. The registry describes possible causes including diabetic vitrectomy, HSV keratitis, HZV keratitis, corneal burns, post-PRK, and post-corneal transplant surgery. The primary efficacy description focuses specifically on individuals with defects following diabetic vitrectomy.
Intervention
The intervention was topical Nexagon, described in a dose-escalation plan progressing from 1µg to 3µg to 10 µg. The registry does not establish which doses participants actually received.
Comparator
The comparator was vehicle alone. The record describes randomized treatment with Nexagon or placebo only within the planned dose groups; it does not provide analyzed comparisons between these treatments.
Primary question
The primary question was whether topical Nexagon preparations would produce greater healing by Day 14 ± 1 than vehicle alone in people with persistent defects following diabetic vitrectomy. Healing was to be assessed by change in lesion pseudo-area between baseline and the Day 14 ± 1 assessment. No efficacy result is reported.
3. Trial Design
The registry describes a phase 2, randomized, double-masked, vehicle-controlled, dose-escalation study with a parallel-group design. The listed masking level is triple. The sponsor was the University of California, San Francisco. The registry-recorded enrollment is 2, and the study status is terminated. The record gives a start date of 2011-11 and a primary completion date of 2014-02.
The planned treatment description includes three Nexagon dose groups, progressing from 1µg to 3µg to 10 µg. For each group, the description states that 18 patients would be randomized to Nexagon and 6 to placebo only. These are planned group descriptions; they do not show that the planned recruitment or allocation took place. The enrollment recorded by the registry is much smaller than the numbers in those descriptions, and the record does not explain the discrepancy or provide an account of the participants’ actual treatment assignments.
The study addressed persistent corneal epithelial defects with several listed underlying contexts, including diabetic vitrectomy, viral keratitis, burns, refractive surgery, and corneal transplant surgery. The primary efficacy description narrows its question to individuals whose defects followed diabetic vitrectomy. The registry does not report whether the broader listed population was enrolled, how participants were distributed across those causes, or whether the primary efficacy population differed from the overall study population.
The registry states that the study was terminated prematurely, the data were never analyzed, and the principal investigator had left the institution, with the data no longer available. It reports no analysis results. Consequently, the registered design describes the intended comparison, not a completed and interpretable treatment-effect analysis.
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: 3 patients were enrolled but only 2 randomized. The third patient was withdrawn from the trial before randomization because we were notified that the study drug had expired and was no longer available.
Overall Study
| Stage | Overall Study |
|---|---|
| STARTED | 2 |
| COMPLETED | 2 |
| NOT COMPLETED | 0 |
Analysis population for the primary outcome, as defined in the registry: The study was terminated prematurely, data were never analyzed; PI has left the institution and data are no longer available.
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: 2 participants were randomized and participated in the study before its premature closure for lack of study drug.
| Characteristic | Unit | Overall Study |
|---|---|---|
| Participants analysed | 2 | |
| Age, Categorical: <=18 years | Participants | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 2 |
| Age, Categorical: >=65 years | Participants | 0 |
| Sex: Female, Male: Female | Participants | 0 |
| Sex: Female, Male: Male | Participants | 2 |
| Region of Enrollment: United States | participants | 2 |
6. Primary Endpoint
The registry lists the primary outcome as Percent Healing of the Corneal Epithelial Defect at Day 14 ± 1 in the Study Eye, measured over 14 ± 1 days.
| Element | Registry entry |
|---|---|
| Result type | N/A |
| Measure of spread | not applicable |
| Unit | not stated |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint was percent healing of the corneal epithelial defect at Day 14 ± 1 in the study eye. The registry defines healing through a comparison of pseudo-area at baseline, just before the first treatment, and at Day 14 ± 1. Pseudo-area was to be measured by an investigator or designated ophthalmologist as the longest lesion diameter multiplied by the longest perpendicular to that diameter.
In general, an endpoint translates a clinical question into an outcome that can be recorded and compared between treatment groups. Measuring the lesion at baseline and at a later assessment was intended to represent the extent of healing over the specified follow-up. The named endpoint is a percentage measure, but the registry gives no participant-level measurements, group summaries, treatment-effect estimate, or statistical uncertainty for it.
The endpoint’s clinical meaning depends on how consistently the lesion dimensions were assessed and how the resulting measurements were analyzed. The record identifies who would measure the pseudo-area and describes the measurement rule, but does not report further measurement procedures, assessor training, reproducibility, or handling of unavailable assessments. It also does not report whether Day 14 ± 1 observations were collected. With no analysis and no data available, the endpoint definition alone cannot establish how much healing occurred or whether the treatment groups differed.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The registry record does not report an efficacy estimate for Nexagon versus vehicle. Its primary outcome description specifies the intended Day 14 ± 1 healing comparison, but the record says the study was terminated prematurely, the data were never analyzed, and the data are no longer available. There are therefore no posted group results from which to describe the observed treatment contrast.
No confidence interval, p-value, or other inferential result for the primary outcome is reported in the registry record. A confidence interval, in general, expresses the statistical uncertainty around an estimated effect under the analysis assumptions. Without an effect estimate and its uncertainty, readers cannot assess the magnitude, direction, or precision of a possible difference in healing. The absence of an analysis is not evidence that the treatments had equal outcomes, nor does it establish that either treatment had a particular effect.
The recorded enrollment is 2. That figure should be read alongside the planned dose-group descriptions, which specify larger intended allocations. The registry does not explain how recruitment ended at the recorded enrollment, whether the enrolled participants received study treatment, or which treatment groups they entered. It also does not report results by dose, cause of the defect, or any other subgroup. The available record therefore cannot support interpretation of the planned dose-escalation comparison.
The registry lists secondary outcomes concerning time to complete re-epithelialization, healing at Day 14 ± 1, change in the rate of re-epithelialization, persistence of complete re-epithelialization, and reduction of the defect at Day 28 ± 2. It reports no analyses for these outcomes. No results are available to determine whether they were measured, how missing assessments were handled, or what comparisons were made.
The registry also includes adverse-event counts, but these do not replace the missing efficacy analysis. They record no serious or other adverse events among the participants listed as at risk in the overall-study group, while the death field has no reported value. The record does not provide enough context to treat these counts as a comprehensive assessment of safety. Overall, the posted information documents the intended design and the study’s termination, but does not answer the efficacy question.
9. Statistical Methods Explained
The registry identifies randomization, masking, a parallel-group model, and vehicle control. In general, random allocation is intended to reduce systematic differences between treatment groups at the start of a trial. Masking is intended to limit the influence of knowledge about treatment assignment on participant behavior, clinical care, measurement, or assessment. A parallel-group design assigns participants to a treatment strategy and follows those groups over the study period. These design features describe the intended approach; they do not demonstrate that the planned study was carried out as designed or that its outcomes were analyzed.
What can randomization establish?
In general, randomization supports a fair comparison when allocation is implemented as planned and outcomes are collected and analyzed appropriately. It does not guarantee that groups will be comparable in every feature, especially when enrollment is limited. The registry does not report the randomization sequence, allocation concealment procedures, actual group assignments, or whether the intended allocation was maintained. The listed study design therefore gives no basis for reconstructing the realized comparison.
The record describes dose escalation from 1µg to 3µg to 10 µg and planned allocations within each dose group. Such a structure can be used to evaluate more than one dose against a control, but the registry does not report the specific rules governing escalation, whether escalation occurred, or any dose-specific analysis. Those details are not reported in the registry record. The planned allocations should not be interpreted as observed enrollment or analyzed group sizes.
What does the endpoint measurement represent?
The primary endpoint uses pseudo-area derived from two lesion dimensions, assessed at baseline and Day 14 ± 1. In general, a change-based outcome compares a follow-up measurement with a starting measurement, while a percentage outcome expresses that change relative to a reference quantity. The registry gives the measurement definition and intended assessment times, but provides no individual observations, group summaries, or analysis formula for calculating the reported endpoint. It also does not report how measurements were handled if an assessment was absent or if a lesion could not be measured.
Clinical measurements can vary between assessors or occasions. In general, consistent measurement procedures help reduce error that can obscure a real difference or make an estimate less precise. The record says the investigator or designated ophthalmologist would measure the lesion, but does not report whether the same assessor evaluated each participant, whether assessments were independently checked, or whether measurement reliability was evaluated. These details are not reported in the registry record.
Why are effect estimates and uncertainty needed?
In general, an effect estimate describes the observed contrast between treatment strategies, while a confidence interval describes the precision of that estimate under the model and assumptions used. A p-value, when reported, relates the observed data to a specified null hypothesis under a statistical procedure. These quantities answer different questions and are most useful when interpreted together with the size and clinical meaning of the effect. None of these primary efficacy results is reported in the registry record, so there is no estimate to interpret and no statistical uncertainty to characterize.
The registry reports zero analyses. It does not identify an analysis model, adjustment variables, analysis population, treatment of repeated measurements, or inferential procedure. Those aspects of the statistical plan are not reported in the registry record. It would therefore be inappropriate to infer that the endpoint was analyzed with a particular model or that an unreported analysis followed the registered design.
What is the role of over-dispersion?
In general, over-dispersion refers to observed variability that exceeds what a statistical model assumes. It matters because a model that understates variability can produce confidence intervals that are too narrow and tests that appear more conclusive than the data justify. The registry does not report a model for the primary endpoint or evidence about its variability. Over-dispersion is therefore a general methodological consideration, not a reported feature of this trial’s analysis.
How should planning illustrations be read?
In general, a sample-size calculation describes how many participants might be needed under stated assumptions to target a specified level of statistical power for a chosen effect. Such calculations are conditional on the assumed effect, variability, allocation, statistical test, and other design choices. They are not measurements of what happened in a trial and do not indicate the probability that a completed study’s finding is correct.
Any planning illustrations associated with the posted results are not observed power. The registry record does not report an analyzed observed effect for this trial, and it says the data were never analyzed. Planning illustrations cannot fill that gap or supply evidence about Nexagon’s effect. The record’s enrollment and planned treatment descriptions should likewise not be taken as a substitute for actual analyzed group data.
10. Multiplicity, Missing Data and Analysis Populations
The registry lists a primary outcome and several secondary outcomes, including time to complete re-epithelialization, healing at Day 14 ± 1, change in the rate of re-epithelialization, persistence of complete healing, and reduction of the defect at Day 28 ± 2. It reports 7 outcome measures and zero analyses. A multiplicity strategy for interpreting several outcomes is not reported in the registry record.
In general, when researchers test multiple outcomes or comparisons, the chance of obtaining at least one apparently unusual result by chance can increase. Statistical plans may address this by specifying which outcome is primary, how other outcomes will be interpreted, or whether adjustments will be made. The registry identifies a primary endpoint, but does not report a complete statistical analysis plan or any multiplicity adjustment. Because no outcome analysis is reported, there are no results for which an adjustment can be evaluated.
The registry says the data were never analyzed and are no longer available. It does not report how missing outcome measurements would have been handled, whether any participants withdrew, or which analysis populations were intended or used. Those details are not reported in the registry record. It is therefore not possible to assess whether the primary outcome was evaluated for all randomized participants, only for those with available measurements, or using another population definition.
In general, missing data can affect both the precision and validity of an estimate, particularly when the reasons for missingness are related to treatment or outcome. Statistical methods can make assumptions about missing observations, but those assumptions must be stated and assessed. The record contains no missing-data analysis or information that would permit such an assessment. No conclusion about the effect of missingness or the analysis population can be drawn from the available registration details.
11. Safety Results
The registry reports serious adverse events as affected participants divided by participants at risk.
| Arm | Participants with serious adverse events | Participants at risk | Percentage |
|---|---|---|---|
| Overall Study | 0 | 2 | 0.0% |
Other (non-serious) adverse events
Participants with at least one non-serious event at or above the registry's 0% reporting threshold.
| Arm | Participants affected of at risk |
|---|---|
| Overall Study | 0 of 2 |
The registry’s overall-study adverse-event entry records 2 participants at risk for serious adverse events and 0 affected. For other adverse events, it likewise records 2 at risk and 0 affected. The death field is null, so a death count is not reported in the registry record; it should not be read as a reported zero. No top serious adverse-event terms are listed.
These entries are counts in the registry, not an estimate of comparative risk between Nexagon and vehicle. The record gives no arm-specific adverse-event results, event descriptions, observation duration, or explanation of how events were collected and classified. It also states that the study was terminated prematurely and that the data were never analyzed and are no longer available. The adverse-event entries therefore have limited context and cannot be taken as a complete account of safety.
In general, a zero recorded event count means that no events were entered in that category for the stated record, not that an event is impossible or that a treatment has been established as safe. Interpretation depends on how many participants were observed, the length and completeness of follow-up, event definitions, and the completeness of reporting. The registry’s counts should be read as the adverse-event information it records, without extrapolating beyond that information.
12. What the Result Does, and Does Not, Mean
The registry establishes that a phase 2 randomized study of Nexagon versus vehicle was registered for persistent corneal epithelial defects, with a planned dose-escalation description and a primary healing outcome at Day 14 ± 1. It also records enrollment of 2 and a terminated status. These registry entries describe the registration and the reported course of the study; they do not constitute an efficacy finding.
The primary endpoint was designed to compare lesion pseudo-area at baseline and Day 14 ± 1. However, the record states that the study ended prematurely, the data were never analyzed, and the data are no longer available. It reports no numerical estimate of healing in either group, no treatment contrast, and no measure of statistical precision. The posted record cannot establish whether Nexagon produced more, less, or similar healing compared with vehicle.
This lack of an analysis is different from a finding of no difference. A study can fail to produce an interpretable result because the data were not analyzed or cannot be accessed; that does not demonstrate that the treatment effect is absent. Conversely, the intended hypothesis and design do not show that a benefit occurred. The registry record supports neither a positive nor a negative efficacy conclusion.
The same caution applies to the listed secondary outcomes and the adverse-event counts. There are no posted secondary-outcome analyses, and the adverse-event information is limited to the registry entries without arm-specific results or further context. These data do not support a broad conclusion about the treatment’s effects or safety.
In general, clinical interpretation requires a clear estimate of the comparison, an assessment of its uncertainty, and consideration of the population and methods used. Here, those analyzed results are not reported in the registry record. The appropriate reading is that the trial’s intended clinical question remains unanswered by the available record, not that the question was resolved in either direction.
13. Why This Trial Matters Statistically
This trial is statistically important as an example of the distinction between a registered design and an analyzable result. Randomization, masking, a comparator, a dose-escalation plan, and a defined primary endpoint describe how a study was intended to answer a question. They do not provide an answer when the data were never analyzed. The registry’s statement that the data are no longer available makes that distinction especially consequential: the intended comparison cannot be reconstructed from the design description alone.
The record also places planned allocations beside a recorded enrollment of 2. That contrast highlights why planned recruitment descriptions should not be treated as realized group sizes. Without reported assignments and outcomes, readers cannot determine whether the planned dose groups were opened, whether participants received the intended interventions, or how the study’s recruitment ended. These gaps affect whether the design can be evaluated as implemented.
Statistical interpretation depends on more than whether an outcome was named. A treatment-effect estimate and its uncertainty are needed to assess the observed comparison, while transparent methods help readers understand how measurements and missing observations were handled. None of those analysis results is available in the registry record. The lack of a result also means that planning assumptions cannot be judged against an observed effect.
For clinical researchers and biostatisticians, the record illustrates the value of preserving and reporting data and analysis methods, including when a trial is terminated. Even an incomplete study can contribute interpretable evidence if its available data, limitations, and analyses are documented. In this case, the registry provides useful information about the question and intended design, but not the evidence needed to estimate the treatment effect.
14. Limitations
- The posted summary statistics are the only data these results rest on; patient-level data, full protocols and statistical analysis plans are not available.
- Recalculated results are simple, unadjusted calculations from posted summaries. They do not replace the sponsor's prespecified analysis.
The central limitation is that the registry states the study was terminated prematurely, the data were never analyzed, and the principal investigator had left the institution, with the data no longer available. This prevents evaluation of the primary endpoint and the listed secondary outcomes. The record reports no effect estimates, uncertainty measures, or outcome analyses.
The registry-recorded enrollment is 2, while the treatment descriptions state planned allocations of 18 patients to Nexagon and 6 to placebo only within each of three dose groups. The record does not explain the difference between planned allocation and recorded enrollment. It does not identify actual treatment assignments, actual doses received, or whether the dose-escalation plan proceeded. The intended design cannot be assumed to describe the trial as implemented.
The primary efficacy description refers to defects following diabetic vitrectomy, while the broader study description lists several possible causes of persistent defects. The record does not report the causes represented among enrolled participants or clarify the size and composition of the primary analysis population. Generalizability to any particular listed cause cannot be assessed.
The registry does not report the statistical analysis plan, analysis populations, handling of missing outcomes, measurement reliability procedures, or a multiplicity strategy. It also gives no explanation for the termination. These details are not reported in the registry record. The adverse-event entries lack arm-specific information and follow-up context, and the death field has no reported value. Taken together, the registry supports a description of the intended study and its reported termination, but not a reliable estimate of efficacy or a comprehensive assessment of safety.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Efficacy and Safety Study of Nexagon for Persistent Corneal Epithelial Defects — NCT01165450.
- Registry record last updated 2015-05-07; status last verified 2015-04.
- Results first posted 2015-04-20.
- 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.
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18. Record Summary
NCT01165450 is a terminated phase 2 randomized, double-masked, vehicle-controlled, parallel-group study sponsored by the University of California, San Francisco. It concerned Nexagon for persistent corneal epithelial defects and included a planned dose-escalation description from 1µg to 3µg to 10 µg. The registry-recorded enrollment is 2.
The primary endpoint was percent healing of the corneal epithelial defect at Day 14 ± 1, assessed using pseudo-area based on lesion dimensions at baseline and follow-up. The registry lists secondary healing and re-epithelialization outcomes but reports zero analyses. It states that the study was terminated prematurely, the data were never analyzed, and the data are no longer available.
Accordingly, the registry record contains no interpretable efficacy estimate or statistical uncertainty for Nexagon versus vehicle. Its adverse-event entry records no serious or other events among the participants listed at risk, while deaths are not reported as a value. The available information describes the intended comparison and reporting limitations, but does not resolve the clinical question.