A Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4 for Treating Corneal Wounds: Complete Statistical Analysis

1. Trial at a Glance

This page covers the registry results for A Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4 for Treating Corneal Wounds (NCT00598871), a randomized phase 2 study. The primary outcome is Number of Participants With Treatment Emergent Adverse Events (TEAEs) After Treatment With Thymosin Beta 4 in the Target Eye of Diabetic Patients During Vitrectomy.

2. Clinical Question

The registry record describes a randomized, double-mask, placebo-controlled Phase 2 study, with a parallel-group model and quadruple masking recorded. It concerns diabetic patients whose corneal wounds followed epithelial debridement during vitrectomy. The study’s stated rationale relates to healing challenges in this population and the possibility that faster wound closure could reduce risks such as infection and corneal scarring. That rationale is not itself evidence that the treatment changed healing or those risks.

The primary outcome is a safety measure: the number of participants with treatment-emergent adverse events (TEAEs) in the target eye. The recorded timeframe is 14 days. Corneal epithelial wound healing at Day 14 is listed as a secondary outcome, but its result is not reported in the registry record. The posted primary outcome therefore does not answer whether wound healing differed between the treatment groups. Nor does the registry record provide an estimable statistical comparison of the primary outcome between groups.

3. Trial Design

This was a randomized, parallel-group Phase 2 study comparing thymosin beta 4 with placebo. The official title describes a double-mask, placebo-controlled, dose-response study. The registry record lists quadruple masking and two arms: active drug and placebo. Although the title refers to dose response, the posted arm descriptions identify one active concentration, 0.01% Tβ4, and placebo at 0.00% Tβ4. Further dose groups are not reported in the registry record.

The active arm received eyedrops in the affected eye at 2 drops 4 times a day for 14 days. The placebo arm received matching eyedrops at the same stated frequency and duration. The study population was diabetic patients undergoing vitrectomy with epithelial debridement, resulting in a corneal wound. The condition recorded is diabetes. The registry lists 12 participants enrolled; the primary outcome record lists 3 participants in the placebo arm and 9 in the active-drug arm.

The study started in 2007-12, and primary completion is recorded as 2009-02. Its status is terminated. The reason for termination is not reported in the registry record, so the status alone does not establish why recruitment or follow-up ended, or whether the decision was related to safety, efficacy, feasibility, or another consideration. The sponsor is ReGenTree, LLC.

The primary outcome was the number of participants with TEAEs in the target eye during 14 days, in an Intent to Treat population using Last Observation Carried Forward. Corneal epithelial wound healing at Day 14 is listed as a secondary outcome. The registry record lists two outcome measures and no analyses. It does not report a full statistical analysis plan, the allocation procedure beyond randomization, or a sample-size justification.

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: Prior to randomization, patients needed to meet specific inclusion and exclusion criteria.There was no run-in period.

Overall Study

Reasons for not completing this period:

Analysis population for the primary outcome, as defined in the registry: Intent to Treat (ITT), Last Observation Carried Forward (LOCF)

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 Number of Participants With Treatment Emergent Adverse Events (TEAEs) After Treatment With Thymosin Beta 4 in the Target Eye of Diabetic Patients During Vitrectomy, measured over 14 days.

The primary endpoint counts participants with treatment-emergent adverse events (TEAEs) in the target eye during the 14-day period after treatment with thymosin beta 4. The outcome is expressed as a number of participants, rather than as a rate, time-to-event measure, or average severity score. The population is described as Intent to Treat with Last Observation Carried Forward, and the endpoint description focuses on diabetic patients who had epithelial debridement during vitrectomy.

A participant count is useful for summarizing how many people experienced at least one event meeting the endpoint definition. It is a safety-oriented outcome: it describes observed event occurrence during the specified period, but does not by itself describe event severity, duration, cause, or clinical importance. Those details are not reported in the primary outcome summary. The registry’s additional safety grouping separates serious adverse events from other adverse events; the posted counts should be read in the context of those categories rather than as a detailed account of every event.

Corneal epithelial wound healing at Day 14 is listed as a secondary outcome. The registry record does not report that outcome’s result. Thus the primary endpoint cannot establish whether wound closure differed between arms, and the posted record does not provide a reported efficacy comparison.

7. Why No Re-analysis Is Shown

8. Statistical Interpretation

9. Statistical Methods Explained

What does a participant count represent?

The primary endpoint is a count of participants with treatment-emergent adverse events in the target eye. In general, this type of endpoint records whether each participant met the event definition during the stated observation period. It does not express how many separate episodes each participant experienced, how long events lasted, or how severe they were unless those details are separately recorded. The registry’s primary outcome is framed as participants with TEAEs, and the posted arm values are counts of participants.

The registry also separates serious adverse events from other adverse events. That distinction is useful because seriousness and event occurrence are not interchangeable descriptions. A count of participants with a serious event says how many met the serious-event category; it does not describe the kinds or clinical course of events. No serious-event terms are listed in the record, and event-level narratives are not reported.

Why is a raw count not a treatment comparison?

In general, groups with different numbers of participants can have different event counts even when their underlying event probabilities are similar. A comparison should account for each group’s size and should use an appropriate statistical method. The registry record lists 3 participants in the placebo arm and 9 in the active-drug arm, and the primary outcome values are 3 and 9, respectively. It does not report an estimable comparison for this binary endpoint. No new proportions or effect estimates are calculated from those counts.

For a binary outcome, an analysis might estimate a difference in event probabilities or another measure of relative occurrence, then quantify uncertainty around that estimate. In general, a confidence interval gives a range of values compatible with the observed estimate and the assumptions of the analysis. Its interpretation depends on the method and study design; it is not a guarantee that the true effect falls within the interval. No such comparative interval is reported in the registry record. A p value, if reported, would address compatibility with a specified null hypothesis under an analysis model, not the clinical importance of an effect. No comparative p value is reported either.

What does the listed analysis population mean?

The primary outcome population is described as Intent to Treat (ITT), Last Observation Carried Forward (LOCF). In general, an ITT approach aims to analyze participants according to their randomized assignment, regardless of whether they completed all assigned treatment. This can preserve the comparison created by randomization, depending on how participants and outcomes are handled. LOCF is a missing-data procedure that carries a participant’s last observed outcome forward to a later time point. It is an imputation assumption, not a newly observed outcome.

The registry record does not explain how many observations were missing, whether LOCF was applied to any participant, or what sensitivity analyses were performed. It does not report further details on handling missing data. LOCF can be problematic in general when an earlier observation is not a reasonable representation of the outcome at the later time point, particularly if the underlying condition can change over time. The validity of that assumption cannot be evaluated from the posted record.

Can the posted results support a power or sample-size conclusion?

The registry record does not report a sample-size justification or the statistical assumptions used to plan enrollment. It also indicates that the two-arm binary comparison was missing or not estimable. No recalculated comparison is presented. Any sample-size illustration based on an observed effect would be a planning exercise, not observed power; in this case, the missing or non-estimable comparison does not furnish a reported effect for that exercise. Observed power is not a substitute for an effect estimate and its uncertainty.

In general, power is a design property that depends on the assumed effect, variability or event frequency, significance level, allocation, and analysis method. It is not a retrospective measure of whether a finding is reliable. The registry record does not report enough detail to assess the study’s planned power or the reasoning behind its enrollment target. It would therefore be inappropriate to infer a design calculation or reconstruct one from the posted participant counts.

What does the record say about multiplicity?

The registry lists a primary safety outcome and a secondary wound-healing outcome. A study that considers multiple outcomes or analyses may need to address multiplicity, since repeated testing can affect the chance of at least one false-positive result. In general, statistical plans can specify which endpoint is primary, how secondary outcomes are interpreted, and whether any adjustment is used. The registry record does not report a multiplicity strategy, an analysis hierarchy, or inferential results for the secondary outcome. No adjustment or testing procedure should be assumed.

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("Placebo", "Active Drug")
n      <- c(3, 9)
events <- c(3, 9)
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  Placebo  3  3  100.0  29.2  100.0  43.9  100.0  39.8  99.4
ARM  Active Drug  9  9  100.0  66.4  100.0  70.1  100.0  69.2  99.7

11. Multiplicity, Missing Data and Analysis Populations

The registry lists the number of participants with TEAEs as the primary outcome and corneal epithelial wound healing at Day 14 as a secondary outcome. It records two outcome measures and no analyses. The secondary wound-healing result is not reported in the registry record. A statistical plan describing how primary and secondary outcomes were to be tested, or whether any adjustment for multiple comparisons was planned, is also not reported.

In general, multiplicity matters when several hypotheses or outcomes are tested: conducting many tests can increase the chance of finding an apparently notable result by chance. A prespecified hierarchy or adjustment can help define how results should be interpreted. No such approach can be inferred from the outcome listings alone, and there are no posted inferential results to evaluate for multiplicity.

The primary outcome population is described as ITT with LOCF. In general, ITT refers to analyzing participants according to randomized assignment, while LOCF carries the last observed measurement forward when a later measurement is missing. The registry does not report the extent or pattern of missing observations, whether LOCF was used for any participant, or sensitivity analyses examining other assumptions. The reasons for missingness and the detailed missing-data procedures are not reported in the registry record.

The registry record does not provide an estimable two-arm comparison for the binary primary outcome. It therefore reports no comparative effect estimate, confidence interval, or p value to interpret. The lack of these statistics should not be treated as evidence of no difference; it means the posted record does not furnish an inferential comparison.

12. Safety Results

The registry reports serious adverse events as affected participants divided by participants at risk.

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 serious adverse-event grouping lists 0 affected participants in the placebo arm and 0 in the active-drug arm. The record lists 3 participants with other adverse events in the placebo arm and 9 in the active-drug arm. The primary outcome likewise reports participant counts for TEAEs, with 3 in the placebo arm and 9 in the active-drug arm. These are counts, not an adjusted comparison or a detailed account of the events.

A serious adverse event is a separate safety category from an adverse event that is not categorized as serious. The recorded zero counts mean that no participants are listed as having a serious event in the posted outcome, not that no adverse events of any kind occurred. The other-adverse-event counts are recorded separately. The record does not give event-level descriptions, severity grades, duration, timing, or attribution, and it does not report death counts. Serious event terms are not listed.

Because the arm sizes differ, the counts should not be compared as if they were rates. The registry record does not report an estimable statistical comparison for the binary primary endpoint. These figures are descriptive of the posted safety results and do not establish causation or rule out uncommon harms.

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

The posted results establish that the registry reports participant counts for the 14-day primary safety outcome: 3 in the placebo arm and 9 in the active-drug arm. The safety grouping reports 0 participants with serious adverse events in either arm, while recording other adverse events in 3 placebo participants and 9 active-drug participants. These observations describe what the registry record reports; they are not, by themselves, an estimate of a treatment effect.

The record does not report a statistically estimable two-arm comparison for the binary primary outcome. It supplies no comparative effect estimate, confidence interval, or p value. Without those results, the size and precision of any difference cannot be assessed. The group counts are not interchangeable with event probabilities, especially given the different arm sizes. No calculation from those counts should be presented as a registry-reported treatment effect.

The primary endpoint concerns adverse events, not corneal wound closure. Although wound healing at Day 14 is listed as a secondary outcome, its result is not reported in the registry record. The posted primary result therefore cannot establish whether thymosin beta 4 changed wound healing, healing time, infection risk, or scarring. The study rationale describes these as reasons for studying a potential treatment, not as outcomes demonstrated by the posted results.

The record also does not state why the trial was terminated, provide a sample-size justification, or detail the statistical analysis plan. The listed ITT/LOCF population description does not reveal how missing observations were handled in practice. These gaps limit interpretation, but they do not justify assuming a particular explanation for termination or missing results.

In general, a small clinical study can contribute descriptive safety observations while leaving comparative effects uncertain. The result should be read as a limited record of participant counts, not as proof that treatment is beneficial, harmful, equivalent to placebo, or free of risk. Any such conclusion would require evidence and analyses that are not reported in the registry record.

14. Why This Trial Matters Statistically

This trial illustrates why a clinical endpoint and a treatment comparison are not the same thing. The primary endpoint is a participant count, which can describe how many people in each arm were recorded with TEAEs. To assess whether event occurrence differed between arms, an analysis must account for the groups being compared and quantify uncertainty. The registry record reports the counts but does not report an estimable two-arm comparison for this binary outcome.

The arm sizes recorded for the primary outcome are different, so raw counts alone can be especially easy to misread. A larger count in one arm does not by itself mean a higher event probability or establish a treatment-related increase. The absence of a reported effect estimate and confidence interval leaves the magnitude and precision of a comparison unresolved. This is a statistical limitation of the posted results, not evidence that the arms were identical.

The trial also distinguishes a safety endpoint from a wound-healing outcome. The primary outcome addresses TEAEs over 14 days; wound healing at Day 14 is listed as secondary but has no reported result. That distinction prevents a safety count from being treated as an efficacy finding. It also shows why outcome definitions and timeframes matter when interpreting clinical research.

Finally, the record’s ITT/LOCF description raises general questions about how missing observations were handled, while the detailed procedures and sensitivity analyses are not reported. The registry record also lists no analyses and does not provide a sample-size justification or multiplicity plan. These omissions make it difficult to judge the intended inferential framework. The case is a reminder that transparent statistical plans and comparative estimates are necessary to move from descriptive counts to a precise interpretation.

15. Limitations

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

The primary outcome is reported as participant counts, but the registry record does not provide an estimable comparison between the two arms. No effect estimate, confidence interval, or p value is reported. The listed arm sizes differ, so the counts alone do not quantify comparative event occurrence. The record also gives no event-level information on the type, severity, timing, duration, or attribution of TEAEs.

The outcome timeframe is 14 days. The posted safety counts therefore describe only the stated period and cannot characterize outcomes beyond it. The record does not report follow-up details beyond the primary timeframe, nor does it provide death counts. The serious-event terms list is empty, and event narratives are not reported.

Corneal epithelial wound healing at Day 14 is listed as a secondary outcome but has no reported result. This leaves the principal healing question unanswered by the posted outcome data. The registry record lists two outcome measures and no analyses, and it does not report a detailed analysis plan, multiplicity procedures, or sample-size justification.

The primary outcome population is described as ITT with LOCF. The number and pattern of missing observations, the actual use of LOCF, and sensitivity analyses are not reported. The trial is marked terminated, but the reason is not reported in the registry record. The record therefore does not support conclusions about why the study ended or whether termination influenced the availability of results.

16. Related Tutorials

17. Related Statistical Calculators

18. Sources

• ClinicalTrials.gov: A Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4 for Treating Corneal Wounds — NCT00598871.
• Registry record last updated 2015-07-08; status last verified 2012-11.
• Results first posted 2010-04-13.
• 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

This randomized, parallel-group Phase 2 study compared 0.01% thymosin beta 4 eyedrops with matching 0.00% placebo in diabetic patients with corneal wounds following epithelial debridement during vitrectomy. Both regimens are described as 2 drops 4 times a day for 14 days. The registry records double masking in the official title and quadruple masking in the design details.

The primary outcome was the number of participants with target-eye TEAEs during 14 days, in an ITT population using LOCF. The posted counts are 3 for placebo and 9 for active drug; the record does not report an estimable two-arm comparison. Serious adverse events are recorded for 0 participants in each arm, and other adverse events for 3 and 9 participants, respectively. Corneal epithelial wound healing at Day 14 is listed as a secondary outcome, but its result is not reported.

The registry lists 12 enrolled participants, a terminated status, and no analyses. The reason for termination and the detailed statistical plan are not reported in the registry record.