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 Study of Thymosin Beta 4 in Patients With Venous Stasis Ulcers (NCT00832091), a randomized phase 2 study. The primary outcome is Safety and Tolerability of Thymosin Beta 4 (Tβ4) Applied to Patients With Venous Stasis (VS) Ulcers for up to 84 Days.
| Feature | Registry value |
|---|---|
| ClinicalTrials.gov identifier | NCT00832091 |
| Phase | Phase 2 |
| Condition | Venous Stasis Ulcers |
| Allocation | Randomized |
| Design model | Parallel |
| Masking | Quadruple |
| Enrollment | 72 |
| Arms in the primary outcome | 2 |
| Lead sponsor | RegeneRx Biopharmaceuticals, Inc. |
| Results posted | Yes |
2. Clinical Question
Population
Patients with venous stasis ulcers. The registry reports enrollment of 72 participants. The posted comparison includes 55 participants in the combined thymosin beta 4 group and 17 in the placebo group.
Intervention
Topical thymosin beta 4 gel, given at three concentrations: 0.01% weight/weight, 0.03% weight/weight, and 0.1% weight/weight. The primary safety result combines the three active doses rather than presenting a separate comparison for each concentration.
Comparator
Topical placebo gel, listed as 0.0% weight/weight thymosin beta 4 gel. The posted comparison is between placebo and the combined active-dose group.
Primary question
What number of treatment-emergent serious adverse events and adverse events was reported during up to 84 days of treatment with thymosin beta 4 at the combined doses, and how should those counts be read alongside the placebo results? Wound closure without drainage by up to 84 days was a secondary question.
This is a safety and tolerability question as well as an efficacy-oriented study question. The primary endpoint concerns counts of events after treatment began or events that worsened after at least one dose. It is not a direct measure of the proportion of participants who experienced an event, because one participant may contribute more than one event. The record also gives adverse-event participant counts separately, which describe participants affected rather than total event counts.
The secondary wound-closure outcome asks whether ulcers achieved closure without drainage during the specified period. Its posted comparison is an unadjusted comparison of the combined active-dose group with placebo. It does not establish how the individual concentrations compare with one another. The registry record does not report a separate dose-specific efficacy conclusion or a formal primary treatment-effect estimate.
3. Trial Design
This was a randomized, parallel-group phase 2 study of topical thymosin beta 4 in patients with venous stasis ulcers. The registry lists the study as completed, with a start date of 2006-07 and a primary completion date of 2009-01. Enrollment is listed as 72. The study title describes a randomized, double-blind, placebo-controlled, dose-response study, while the registry’s masking classification is quadruple. Which specific groups of people were masked is not reported in the registry record.
The intervention comprised three concentrations of thymosin beta 4 gel: 0.01% weight/weight, 0.03% weight/weight, and 0.1% weight/weight. Placebo gel was listed as 0.0% weight/weight. The arm descriptions describe three groups, each with active treatment and placebo, while the posted outcome results combine the three active doses into one thymosin beta 4 group. Consequently, the displayed comparison does not provide dose-by-dose estimates.
For the posted outcomes, the placebo group has 17 participants and the combined thymosin beta 4 group has 55. The primary endpoint covers treatment-emergent serious adverse events and adverse events during up to 84 days. The secondary outcome measures wound closure without drainage over up to 84 days. The record identifies the primary population as analysis per protocol and intention-to-treat using last observation carried forward, but does not explain how those populations and procedures were applied to each result.
The registry record does not report a sample-size justification, the intended statistical model for the primary count endpoint, or a protocol-level plan for comparing the three concentrations. It also does not provide the identities of the masked parties. Those details cannot be inferred from the randomized and masking classifications alone.
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 need to meet specific inclusion and exclusion criteria. There was no wash-out or run-in periods
Overall Study
| Stage | Placebo | Thymosin Beta 4 (Tβ4) at 3 Doses |
|---|---|---|
| STARTED | 17 | 55 |
| COMPLETED | 12 | 53 |
| NOT COMPLETED | 5 | 2 |
Reasons for not completing this period:
| Reason | Placebo | Thymosin Beta 4 (Tβ4) at 3 Doses |
|---|---|---|
| Adverse Event | 1 | 1 |
| Protocol Violation | 1 | 0 |
| Withdrawal by Subject | 2 | 1 |
| Prohibited Medication | 1 | 0 |
Analysis population for the primary outcome, as defined in the registry: Analysis per protocol, ITT, using 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.
| Characteristic | Unit | Placebo | Thymosin Beta 4 (Tβ4) at 3 Doses | Total |
|---|---|---|---|---|
| Participants analysed | 17 | 55 | 72 | |
| Age, Categorical: <=18 years | Participants | 0 | 0 | 0 |
| Age, Categorical: Between 18 and 65 years | Participants | 9 | 39 | 48 |
| Age, Categorical: >=65 years | Participants | 8 | 16 | 24 |
| Sex: Female, Male: Female | Participants | 12 | 28 | 40 |
| Sex: Female, Male: Male | Participants | 5 | 27 | 32 |
| Region of Enrollment: Poland | participants | 6 | 38 | 44 |
| Region of Enrollment: Italy | participants | 11 | 17 | 28 |
6. Primary Endpoint
The registry lists the primary outcome as Safety and Tolerability of Thymosin Beta 4 (Tβ4) Applied to Patients With Venous Stasis (VS) Ulcers for up to 84 Days, measured over Up to 84 days.
| Element | Registry entry |
|---|---|
| Result type | Number |
| Measure of spread | not applicable |
| Unit | SAEs and AEs |
| Endpoint classification | not reduced to a single comparison |
The primary endpoint is the number of treatment-emergent serious adverse events and adverse events associated with thymosin beta 4 gel at the three doses combined, in patients with venous stasis ulcers, during up to 84 days. An event qualifies as treatment-emergent if it begins after at least one dose or if its severity worsens after a dose. A pre-existing condition is not an adverse event unless it worsens during the study, in which case it may be considered one.
Counting adverse events is one way to describe the overall event burden recorded during treatment. It preserves repeated events: a participant can experience more than one event, so an event total is not interchangeable with the number of participants affected. The registry also presents participant counts for people with serious adverse events and other adverse events, which are a different summary. Those summaries should be read according to what they count, rather than treated as if they were the same endpoint.
Safety and tolerability are central to evaluating an investigational treatment because they describe unwanted events recorded during exposure. They do not by themselves establish whether treatment caused an event, and an event count does not convey its severity, duration, or clinical context unless those details are reported. The registry record gives no dispersion measure or formal inferential comparison for the primary event totals. A comparative primary effect estimate and its precision are therefore not reported in the registry record.
7. Why No Re-analysis Is Shown
8. Statistical Interpretation
The primary result is reported as event totals: 24 in the placebo group and 104 in the combined thymosin beta 4 group. These are counts, not participant-level risks or event rates. The groups differ in size, and the record does not provide person-time or an adjusted analysis that would account for exposure duration. The totals alone therefore do not establish a comparative treatment effect. A confidence interval or p-value for the primary count comparison is not reported in the registry record.
The adverse-event summary also reports participants affected: serious adverse events were reported for 1 of 17 participants in the placebo group and 3 of 55 in the combined thymosin beta 4 group. Other adverse events were reported for 11 of 17 and 35 of 55, respectively. These figures are participant counts, not the same quantities as the primary event totals. The registry’s serious-event listing includes connective tissue, inflammation; increased transamines; lymphangitis; and skin ulcer, with the percentages recorded for those terms. Death counts are not reported in the registry record.
For wound closure without drainage, 4 of 17 placebo participants and 12 of 55 participants in the combined active group were reported as having the outcome. The unadjusted risk difference is -0.017, with a 95% confidence interval from -0.246 to 0.212 and p = 0.882. The interval includes no difference and also spans effects in either direction. This estimate is imprecise: the data do not narrowly locate the underlying difference. The unadjusted p-value is not evidence that the groups are equivalent, and the confidence interval does not show that all clinically relevant differences have been excluded.
The comparison pools three active concentrations, so it cannot answer whether outcomes differed by dose. The small number of participants in the placebo group also means the secondary comparison is uncertain. The registry does not report an adjusted analysis or a multiplicity procedure for the secondary outcome. Accordingly, the posted wound-closure result should be read as an exploratory, unadjusted comparison, not as a stand-alone definitive conclusion.
The primary safety outcome and secondary wound-closure outcome address different questions. Neither can substitute for the other: a count of adverse events does not measure wound closure, and the wound-closure comparison does not summarize safety. The registry record does not report a formal inferential analysis for the primary endpoint, so the posted primary totals support description rather than a precise statistical claim about the difference between treatments.
9. Statistical Methods Explained
Statistical interpretation depends on what each outcome counts, how participants are grouped, and whether an estimate includes uncertainty. The posted results use different summaries for safety and wound closure, so they should not be treated as if they were on a common scale.
What does a count endpoint describe?
The primary endpoint counts treatment-emergent serious adverse events and adverse events. Event counts can include repeated events in the same participant. Thus, a total number of events is not the same as the number of participants with at least one event. The record gives both kinds of information: primary event totals, and separate participant counts for those affected by serious or other adverse events.
General statistical explanation: count outcomes often vary more than a simple model assuming equal mean and variance would allow, particularly when a few participants contribute multiple events. This is called over-dispersion. An analysis may need to account for that pattern, as well as different follow-up time or exposure across participants. The registry record does not report the primary count model, a dispersion estimate, participant-level event distributions, or person-time. It is therefore not possible to reconstruct a formal comparison from the posted totals alone.
How should the wound-closure estimate be read?
The secondary endpoint is binary: a participant either had wound closure without drainage by up to 84 days or did not have that outcome recorded. The posted risk difference is -0.017 for the combined thymosin beta 4 group compared with placebo. A risk difference expresses the difference between the two groups’ observed proportions, on the probability scale. The 95% confidence interval, from -0.246 to 0.212, describes statistical uncertainty in that estimate under the method used for the recalculation. Because it covers zero and extends in both directions, the estimate is compatible with a range of possible underlying differences.
General statistical explanation: a confidence interval is a range of estimates that reflects uncertainty from sampling under specified assumptions. It is not a guarantee that the true effect lies within the particular interval, and its width matters as much as whether it includes a no-difference value. Here the interval is wide enough that the point estimate should not be treated as precise. The unadjusted p-value of 0.882 summarizes how unusual a result at least this discordant with a no-difference model would be under that model; it does not give the probability that treatment has no effect.
The posted risk ratio is 0.927, with a confidence interval from 0.344 to 2.501, and the odds ratio is 0.907, with a confidence interval from 0.249 to 3.296. These alternative scales also have intervals extending across their no-association values. They are unadjusted recalculations from the posted summary data, not reported sponsor analyses. The registry reports no analysis for the secondary outcome, and the record does not report a sponsor estimate to compare with these calculations.
Why does combining doses matter?
The three active concentrations are pooled for the posted treatment comparison. Pooling gives one overall comparison but does not preserve a separate effect estimate for each dose. It also does not test whether the response changes across concentrations. The registry record does not report a dose-response model or a planned trend test, so a dose-response conclusion cannot be drawn from the pooled result.
What do the planning illustrations mean?
The posted planning illustration uses the observed wound-closure effect as a starting point and assumes two-sided significance level 0.05, equal allocation, and a normal approximation. It reports participants per arm for 80% power and participants per arm for 90% power when planning for 100% of the observed effect, 75% of the observed effect, or 50% of the observed effect. These are planning illustrations based on the recalculated observed effect; they are not the trial’s original design justification, and they are not observed power. The registry record does not report the trial’s sample-size justification.
General statistical explanation: power is a design property defined for a specified effect, variability, test, and sample size. Calculating power after observing a result does not make the result more or less reliable. Planning for a smaller effect generally requires more participants when other assumptions remain fixed, but such illustrations rely on assumptions that may not match a future study. The values should therefore be treated as conditional planning scenarios, not as a recommendation or as proof that the current study was adequately or inadequately powered.
What cannot be inferred from the reported analyses?
The record lists no reported analyses for the secondary outcome and no comparative inferential result for the primary count outcome. It does not state whether interim analyses were conducted, how missing outcome data were handled for each endpoint, or what adjustment, if any, was planned for multiple comparisons. Those details are not reported in the registry record. The analysis population description mentions per-protocol, intention-to-treat, and last observation carried forward, but does not specify which result uses which population or how the procedure was implemented. Statistical interpretation should remain limited to the stated summaries and the unadjusted recalculations.
10. Multiplicity, Missing Data and Analysis Populations
The registry record does not report a multiplicity adjustment or explain how formal testing was organized across outcomes, doses, or comparisons. There is one posted secondary endpoint, but the intervention includes three active concentrations and the reported outcome comparison combines them. The record does not say whether dose-specific comparisons or additional analyses were prespecified. Without that information, the role of the secondary comparison in any testing hierarchy is not reported in the registry record.
General statistical explanation: if multiple hypotheses are tested, the chance of at least one apparently unusual result can increase. Multiplicity procedures control or otherwise address that issue according to a planned strategy. An unadjusted p-value does not account for other tests that may have been considered. The wound-closure p-value is therefore best interpreted as a single unadjusted statistic, not as evidence that a broader family of comparisons has been resolved.
Missing-data handling is also unclear. The primary population description mentions analysis per protocol, intention-to-treat, and last observation carried forward, but does not identify how those approaches map to the posted outcomes, how many participants had missing observations, or how the carry-forward procedure was applied. The registry record does not report these details. Last observation carried forward is a method for filling in missing follow-up values by carrying a prior observation forward; general statistical explanation: this can impose assumptions about what happened after the last recorded value, and those assumptions may not match the unobserved course.
The record does not report whether interim analyses were conducted, how randomization was generated or concealed, or whether the analysis populations were defined before the results were known. These omissions do not establish that such procedures were absent; they mean the information is not reported in the registry record. The available data consequently support a cautious reading of the posted summaries, without attributing an undocumented analysis plan.
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 |
|---|---|---|---|
| Placebo | 1 | 17 | 5.9% |
| Thymosin Beta 4 (Tβ4) at 3 Doses | 3 | 55 | 5.5% |
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 |
|---|---|
| Placebo | 11 of 17 |
| Thymosin Beta 4 (Tβ4) at 3 Doses | 35 of 55 |
Most frequent serious adverse event terms
| Event term | Organ system | Placebo | Thymosin Beta 4 (Tβ4) at 3 Doses |
|---|---|---|---|
| Connective tissue, inflammation | Musculoskeletal and connective tissue disorders | 1 of 17 | 2 of 55 |
| Skin Ulcer | Skin and subcutaneous tissue disorders | 0 of 17 | 2 of 55 |
| Increased Transamines | Investigations | 1 of 17 | 0 of 55 |
| Lymphangitis | Infections and infestations | 1 of 17 | 0 of 55 |
Most frequent non-serious adverse event terms
| Event term | Organ system | Placebo | Thymosin Beta 4 (Tβ4) at 3 Doses |
|---|---|---|---|
| Red blood cell sedimentation rate increased | Investigations | 0 of 17 | 6 of 55 |
| Pruritus | Skin and subcutaneous tissue disorders | 1 of 17 | 4 of 55 |
| Inflammation | General disorders | 1 of 17 | 4 of 55 |
| blood creatinine phosphokinase increased | Investigations | 1 of 17 | 3 of 55 |
| Pain in extremities | Musculoskeletal and connective tissue disorders | 1 of 17 | 3 of 55 |
| nasopharyngitis | Infections and infestations | 1 of 17 | 2 of 55 |
| upper respiratory infection | Infections and infestations | 0 of 17 | 3 of 55 |
| urinary tract infection | Infections and infestations | 0 of 17 | 3 of 55 |
| erythema | Skin and subcutaneous tissue disorders | 0 of 17 | 3 of 55 |
| Varicose ulceration | Vascular disorders | 1 of 17 | 2 of 55 |
Serious events with the highest arm-level rate: connective tissue, inflammation (5.9%), increased transamines (5.9%), lymphangitis (5.9%), skin ulcer (3.6%).
The adverse-event summary reports serious adverse events in 1 of 17 placebo participants and 3 of 55 participants receiving thymosin beta 4 at the three doses combined. It reports other adverse events in 11 of 17 and 35 of 55 participants, respectively. These are counts of participants affected, not counts of all events; one person may have experienced more than one event. The primary endpoint’s totals of 24 and 104 are event counts and should not be substituted for these participant counts.
The listed serious-event terms include connective tissue, inflammation; increased transamines; lymphangitis; and skin ulcer, with the percentages recorded in the registry. The registry record does not report deaths. These summaries do not, by themselves, establish whether treatment caused an event, and they do not provide a complete account of severity, duration, or individual clinical context. The registry record does not report a formal comparative statistical analysis of the primary safety counts. The figures should therefore be read descriptively, with attention to the different group sizes and to the distinction between event totals and participants affected.
12. What the Result Does, and Does Not, Mean
The posted results describe adverse-event counts and a secondary wound-closure comparison in a randomized phase 2 study. The primary safety totals are 24 events in the placebo group and 104 in the combined thymosin beta 4 group. Separate participant-level safety summaries report affected participants, which are not interchangeable with those event totals. The registry does not provide a formal primary comparison or an uncertainty interval for the count outcome, so the totals do not by themselves quantify a treatment effect.
For wound closure without drainage, the unadjusted estimate is close to no difference, but its confidence interval is broad and includes possible differences in either direction. The result is not precise enough to establish equality, and it does not exclude potentially important differences. Because this result combines three active concentrations and is unadjusted, it also cannot identify a dose-specific pattern or serve as definitive evidence across multiple comparisons.
These results do not establish that thymosin beta 4 caused or prevented the reported adverse events, nor do they establish a treatment effect on wound closure. The posted data alone do not reveal the full clinical context of events, the consequences of missing observations, or whether the analysis approach was prespecified. The record’s population description refers to per-protocol and intention-to-treat analyses using last observation carried forward, but the implementation details are not reported in the registry record.
General statistical explanation: absence of a statistically clear difference is not the same as proof of no difference. Establishing equivalence or non-inferiority requires a defined margin and an analysis designed for that purpose; such a margin is not reported in the registry record. The results are best understood as limited descriptive and unadjusted evidence, with uncertainty that remains substantial for the secondary comparison.
13. Why This Trial Matters Statistically
This trial illustrates why the endpoint’s statistical form matters. Its primary measure is an event count, while the safety summary also includes the number of participants affected. Those measures answer different questions: repeated events can contribute several times to a total, whereas a participant-level summary counts each affected person according to whether an event occurred. Treating them as interchangeable could distort interpretation.
The study also demonstrates the limits of a pooled dose comparison. Combining three concentrations produces an overall active-treatment summary but obscures potential variation among doses. A pooled estimate cannot establish a dose-response relationship, and a dose-response title does not replace a reported dose-specific analysis.
For the secondary binary outcome, the confidence interval is as important as the point estimate and p-value. Its width indicates considerable uncertainty, while its inclusion of no difference prevents a clear separation of the groups. At the same time, that result is not evidence of equivalence. A non-significant unadjusted result cannot settle whether smaller or larger effects remain plausible.
Finally, registry summaries do not always include the full analysis plan or all inferential results. Here, a formal primary count comparison, the handling of multiplicity, endpoint-specific missing-data procedures, and the details of the stated analysis populations are not reported in the registry record. Recognizing such gaps is part of statistical interpretation: it prevents descriptive counts and exploratory recalculations from being mistaken for a complete prespecified analysis.
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 principal limitation for interpretation is that the registry reports primary event totals without a formal comparative estimate, dispersion measure, or confidence interval. The groups also have different participant counts, and no person-time summary is reported. The event totals cannot therefore be read as directly comparable event rates or as a complete inferential analysis.
The active-treatment results combine three concentrations. This prevents assessment of each concentration separately and makes a dose-response interpretation unavailable from the posted comparison. Although the study title describes a dose-response design, the registry record does not report the dose-specific statistical analysis or a dose-response model.
The secondary wound-closure estimate is an unadjusted recalculation from the posted summary counts. It has a broad confidence interval, and the registry lists no reported analyses for this endpoint. No multiplicity procedure is reported. The result should not be treated as a confirmatory analysis or as evidence of equivalence.
The analysis-population description refers to per-protocol and intention-to-treat analyses using last observation carried forward, but does not clarify which population or missing-data approach produced each result. The number and pattern of missing observations, the endpoint-specific implementation, and sensitivity analyses are not reported in the registry record. Details of allocation concealment, who was masked, and interim analyses are also not reported in the registry record. These omissions limit assessment of the methods but do not establish that a procedure was not used.
15. Related Tutorials
16. Related Statistical Calculators
17. Sources
- ClinicalTrials.gov: Study of Thymosin Beta 4 in Patients With Venous Stasis Ulcers — NCT00832091.
- Registry record last updated 2010-03-30; status last verified 2010-03.
- Results first posted 2010-03-24.
- 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
NCT00832091 is a completed randomized, parallel-group phase 2 study of topical thymosin beta 4 in patients with venous stasis ulcers. The registry lists enrollment of 72, a start date of 2006-07, and primary completion in 2009-01. The study compared placebo with three active gel concentrations, while the posted results combine the active doses.
The primary endpoint counts treatment-emergent serious adverse events and adverse events during up to 84 days. The posted totals are 24 for placebo and 104 for combined thymosin beta 4. Wound closure without drainage by up to 84 days is the secondary endpoint; its unadjusted comparison is uncertain and does not establish equivalence or a dose-specific effect. Formal comparative analysis of the primary count endpoint, multiplicity procedures, and endpoint-specific missing-data details are not reported in the registry record.