NCT00832091 was a phase 2 dose-escalation study of RGN-137, a topical gel containing a synthetic copy of full-length, 43-residue thymosin beta-4, added to standard venous-ulcer care. Its primary purpose was safety and tolerability, not proof of wound-healing efficacy. The registry’s pooled active groups had 12/55 wounds closed without drainage by day 84 versus 4/17 under placebo, while the middle concentration showed a small, non-monotonic arm-level signal. Company filings state that formal efficacy comparisons were not statistically significant. The trial therefore supports limited short-term safety observations and an exploratory hypothesis; it does not establish wound-healing benefit, and it is not evidence for a material sold or labeled as TB-500 or for another thymosin fragment.[1][2][3]
Study at a glance
| Field | Study record |
|---|---|
| Research question | Was topical full-length thymosin beta-4 gel acceptably tolerated, and did any of three concentrations show a wound-closure signal when added to standard venous-ulcer care? |
| Design | Phase 2, multicenter, double-blind, placebo-controlled, sequential dose-escalation/dose-response study at five Italian and three Polish sites |
| Population | Registry: 72 participants analyzed as 17 placebo and 55 pooled active; paper abstract: 73 enrolled and randomized; adults with chronic venous stasis ulcers |
| Intervention | Historical study identifiers: RGN-137 full-length Tβ4 gel at 0.01%, 0.03%, or 0.1% w/w, alongside standard wound care |
| Comparator | Vehicle placebo gel plus the same background wound care; placebo participants from dose cohorts were combined |
| Duration | Up to 84 treatment days, with adverse-event reporting through 99 days |
| Primary outcome | Safety and tolerability, summarized as adverse events; wound closure without drainage was secondary |
| Registration | NCT00832091; completed; first registered after the study began; structured results posted |
| Publication | Guarnera, DeRosa, and Camerini, Annals of the New York Academy of Sciences 2010; PMID 20536470; DOI 10.1111/j.1749-6632.2010.05490.x |
| Sponsor/funding | RegeneRx Biopharmaceuticals registered sponsor; Sigma-Tau collaborator; RegeneRx filings say Sigma-Tau conducted/funded or funded and co-managed the European trial |
| Results-posting state | Results first posted March 24, 2010; registry pools all three active concentrations for outcomes and adverse events |
The article and registry state the historical concentrations and once-daily gel schedule. Those facts identify the trial; they are not wound-care, preparation, application, concentration-selection, or treatment instructions.
A TB-500 label does not establish study-drug identity
The paper defines the test article as a synthetic copy of naturally occurring thymosin beta-4, a 43-amino-acid peptide, formulated as RGN-137 topical gel.[1] A “TB-500” label alone does not establish sequence or formulation identity to that test article, so the trial cannot transfer findings to a material sold or labeled as TB-500, a fragment, or another formulation.
Even an accurate “thymosin beta-4” label would not by itself establish equivalence. Concentration, excipients, manufacturing, purity, stability, container, application site, standard-care context, and lot attributes are part of the study identity. No result can be transferred to an injectable, oral, compounded, fragmentary, blended, or catalog product.
Background wound care was part of every arm
Standard care included compression, dressings, removal of devitalized tissue when needed, and infection control. Study gel was added to that care. Any observed closure occurred under the combined protocol and cannot be attributed to gel while erasing compression and wound management.[1][4]
The study used sequential concentration cohorts, with participants randomized within the dose-escalation structure to active gel or vehicle. The registry later combined placebo participants and combined all active concentrations in its posted tables. Pooling improves the size of a broad safety comparison but hides whether benefit or harm varies by concentration.
Enrollment differs between the article and registry
The peer-reviewed abstract says 73 patients were enrolled and randomized across eight European sites. ClinicalTrials.gov reports actual enrollment of 72. Its analyzed arms comprise 17 placebo and 55 active participants, which total 72.[1][2]
The public sources do not explain the extra person in the article’s 73. Possibilities such as consent without analysis or late exclusion should not be invented. The defensible wording is “73 reported enrolled/randomized in the publication; 72 reported and analyzed in the registry,” followed by the source-specific denominators.
The registry says 12/17 placebo participants and 53/55 pooled active participants completed. Five placebo and two active participants did not. Reasons under placebo were one adverse event, one protocol violation, two withdrawals, and one prohibited medication; active reasons were one adverse event and one withdrawal. Differential completion matters when interpreting a small wound-closure study.
Primary outcome was safety, not wound closure
ClinicalTrials.gov labels safety and tolerability through day 84 as primary. Its primary table reports 24 adverse events under placebo and 104 across the three active concentrations. These are numbers of events, not numbers of participants, so 104 cannot be described as 104 people or as a 189% event rate.[2]
Participant-level adverse-event tables show serious events in 1/17 placebo participants and 3/55 pooled active participants. Other nonserious events affected 11/17 and 35/55, respectively. The record describes the serious events as unrelated to study treatment. The paper’s abstract calls the safety profile acceptable and comparable to placebo, while the small groups and broad pooling limit precision.[1][2]
ClinicalTrials.gov leaves the all-cause-mortality cells unpopulated. The accurate statement is that mortality data are not supplied in that table, not that the registry proves no deaths. Safety follow-up through 99 days cannot address uncommon, delayed, or repeated-exposure harms.
Secondary wound-closure result was formally null
The registry’s secondary endpoint was complete wound closure without drainage by day 84. It reports closure in 4/17 placebo participants, or 23.5%, and 12/55 pooled active participants, or 21.8%. Pooled this way, the active rate was not higher than placebo.[2]
Company disclosures report closure proportions of 16%, 33%, 17%, and 24% for the low, middle, high, and placebo groups. Reconciled to the registry totals, those rounded percentages correspond approximately to 3/19, 6/18, 3/18, and 4/17.[2][3] The middle concentration had the highest numerical rate, but the lower and higher concentrations were below placebo and there was no monotonic dose-response pattern. Six versus four closures is too sparse to carry a confident efficacy claim.
RegeneRx’s securities filing explicitly states that efficacy results did not reach statistical significance and did not trigger a contractual milestone tied to positive phase 2 results. That disclosure is an important counterweight to the article abstract’s more favorable language that 0.03% “may” accelerate healing and that roughly one-quarter healed, particularly among smaller or less severe ulcers.[1][3]
Dose and subgroup signals are hypothesis-generating
The publication emphasizes the middle concentration and smaller or moderate ulcers. Such patterns can generate a follow-up hypothesis, but they arise from very small arms, multiple concentrations, wound-size and severity subgroups, and only a few closure events. The public abstract does not provide a precise multiplicity strategy or adequately powered confirmatory subgroup test.[1]
A credible confirmatory trial would prospectively define a primary healing outcome and subgroup, use enough participants, retain the standard-care comparator, disclose missing data, and reproduce the effect. This phase 2 study did not do that. “Potential to accelerate” is a research interpretation, not demonstrated effectiveness.
Registration timing, sponsor, and funding
The registry lists a July 2006 start, January 2009 primary completion, and January 29, 2009 first posting. Registration therefore occurred after enrollment began and around primary completion rather than prospectively before the first participant. Structured results were posted in March 2010.[2]
ClinicalTrials.gov names RegeneRx Biopharmaceuticals as sponsor and Sigma-Tau as collaborator. RegeneRx’s SEC filings say Sigma-Tau conducted and funded, or funded and co-managed, the European phase 2 trial. They also describe a commercial license and milestone context. These are material financial and operational roles, not neutral background.[2][3]
Statistical significance, effect, uncertainty, and importance
- Statistical significance: sponsor disclosures state that no formal efficacy result was statistically significant.
- Effect size: pooled closure was 12/55 active versus 4/17 placebo; the exploratory middle arm was about 6/18 versus 4/17.
- Uncertainty: only 16 total closures occurred in the registry population, arm sizes were 17–19, attrition differed, and subgroup analyses were sparse.
- Clinical importance: complete closure matters to patients, but this trial did not demonstrate a reliable incremental benefit over standard care and vehicle.
Important limitations
- The paper reports 73 enrolled/randomized while the registry reports and analyzes 72, without explaining the difference.
- Registration occurred after study initiation and near primary completion.
- The primary outcome was safety; healing was secondary.
- Registry pooling obscures concentration-specific efficacy and safety.
- The apparent middle-dose pattern was non-monotonic and based on six closures.
- Standard wound care contributed in every arm.
- Small groups and short follow-up cannot characterize uncommon or delayed harms.
What this study does not prove
NCT00832091 does not prove that RGN-137 improves venous-ulcer closure over vehicle and standard care, that 0.03% is an effective concentration, that smaller ulcers reliably respond, or that any effect persists or reduces infection, recurrence, hospitalization, or amputation. The formal efficacy evidence was null and the favorable dose/subgroup patterns remain exploratory.[1][2][3]
It also provides no evidence for a material sold or labeled as TB-500, a thymosin fragment, an injectable preparation, another gel, another concentration, a blend, or a catalog material. The studied full-length 43-residue peptide and finished topical formulation are essential boundaries.
Frequently asked questions
Were 72 or 73 participants enrolled?
The publication abstract says 73 enrolled and randomized; the registry reports 72 and its arm denominators total 72. Public sources do not explain the difference.[1][2]
What was the trial’s primary outcome?
Safety and tolerability through 84 days were primary. Wound closure without drainage was a secondary efficacy outcome.[2]
Did pooled active treatment improve complete closure?
No. Registry closure was 12/55 pooled active versus 4/17 placebo, about 22% versus 24%.[2]
Why did the middle concentration attract attention?
About 6/18 middle-concentration participants healed versus 4/17 placebo, while lower and higher active arms each had about three closures. The pattern was small, non-monotonic, and not statistically confirmatory.[2][3]
Do 104 active adverse events mean 104 participants were harmed?
No. That registry field counts events across 55 active participants. Participant-level tables report nonserious events in 35/55 and serious events in 3/55.[2]
Was the trial prospectively registered?
No. It started in 2006 and first appeared on ClinicalTrials.gov in January 2009, around primary completion.[2]
Does a TB-500 label establish identity to the full-length study drug?
No. The trial studied a synthetic copy of the full 43-residue peptide in RGN-137 gel. A TB-500 label cannot establish identity or effects for that sequence and formulation, a fragment, another supplier, or another lot.[1]