Peptide LibraryAdverse events, serious adverse events and discontinuations
Insufficient information to assessSafety outcome · 8 studies · 318 participants
Not enough evidence to tell
The certainty of evidence about the safety of thymosin beta-4 in people is very low. Small, short trials of the injected form and of eye drops or skin application reported mostly mild or moderate side effects and no serious ones. However, these were given only as brief summaries without comparing treated and placebo groups. This does not show that thymosin beta-4 is safe; it means rare, delayed or longer-term harms have not been properly studied.
What the research measured: Adverse events, serious adverse events and dose-limiting toxicities were reported narratively. In two intravenous phase I trials in healthy volunteers (four cohorts of 10; 54 single-dose plus 30 multiple-dose subjects), adverse events were mild or moderate and no dose-limiting toxicities or serious adverse events occurred, but results were not given by arm. A topical venous ulcer trial (73 randomized) reported a safety profile comparable to placebo. A dry eye trial (72 randomized) reported no adverse events observed. A 9-patient severe dry eye trial and a 10-patient cell-therapy pilot described the treatment only as safe or well tolerated, with no counts. Two registered trials (12 and 18 enrolled) reported no safety data. Discontinuations were not reported in any study.
What remains unknown: It is unknown how adverse event rates compare between thymosin beta-4 and placebo, because no arm-level counts were reported. Discontinuation rates are unknown. Safety beyond a few weeks to months of follow-up has not been studied, nor has repeated or long-term use. Effects in patients with serious illness, older adults, pregnant people and children are unknown, as is immunogenicity (anti-drug antibody results were not reported). Results of two registered trials, one terminated, are unavailable. Safety of non-pharmaceutical products is also unknown.
Reviewers’ note: At least one included study has no risk-of-bias assessment, so no certainty rating is given.
How the certainty was judged
| Domain | Judgment | Why |
|---|---|---|
| Starting level | — | |
| Risk of bias | — | All contributing trials are available only as abstracts or registry entries. Risk-of-bias judgments for the safety outcomes range from some concerns to high. Randomization, blinding and allocation details cannot be verified, and adverse events are mostly described narratively without arm-level breakdown. |
| Inconsistency | — | The trials with any safety reporting all describe adverse events as absent, mild to moderate, or comparable to placebo, with no serious adverse events reported. There is no apparent disagreement, although narrative reporting limits formal assessment. |
| Indirectness | — | Healthy volunteers and several different conditions were studied by IV, topical skin and eye routes. One study used Tβ4-primed cells, not Tβ4 itself. Discontinuations were not reported by any study. |
| Imprecision | — | No study reported adverse event counts by arm or any effect estimate for active versus placebo. Total contributing samples are small, around 300 people across short phase I/II trials. That is far too few to detect uncommon or delayed harms, and zero serious events in such samples is uninformative. |
| Publication bias | — | Two registered placebo-controlled safety trials have no available results in the record; one was terminated early. Most other trials are small, likely commercially sponsored phase I/II studies (e.g., RGN-259) reported only in abstracts, with funding not stated. |
Included studies
- A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers. (Randomized controlled trial)
- The effect of thymosin treatment of venous ulcers. (Randomized controlled trial, 73 participants)
- Safety and efficacy of autologous thymosin β4 pre-treated endothelial progenitor cell transplantation in patients with acute ST segment elevation myocardial infarction: A pilot study. (Randomized controlled trial, 10 participants)
- A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. (Randomized controlled trial)
- Thymosin beta 4 ophthalmic solution for dry eye: a randomized, placebo-controlled, Phase II clinical trial conducted using the controlled adverse environment (CAE™) model. (Randomized controlled trial)
- Thymosin β4 significantly improves signs and symptoms of severe dry eye in a phase 2 randomized trial. (Randomized controlled trial, 9 participants)
- A Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4 for Treating Corneal Wounds (Other design, 12 participants)
- Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy : SEER-1 (Other design, 18 participants)
Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · GRADE (handbook, 2013) · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.