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safety record

Thymosin beta-4: what has been measured about safety

The safety record for thymosin beta-4, read as a record: the one trial that published an adverse event count, how far the injected route's record actually reaches, and the growth-factor question the laboratory work raises.

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Thymosin beta-4 has something most compounds on this site do not: a published human trial that counted adverse events and printed the numbers. It is a Phase 3 study of a 0.1 per cent ophthalmic solution in neurotrophic keratopathy, it enrolled 18 people against a planned 46, and it reports 16 adverse events across 7 of them [2].

That is a real observation and it is a very small one, in an eye, over weeks, using a manufactured ophthalmic formulation. The route this protein is bought for is injection, and the injected record runs differently: the two US registrations that would have produced systematic human safety data for an injected form were both withdrawn before enrolling anyone [14] [15], and the completed injected trials elsewhere have posted nothing [19] [20] [21] [22].

So this page sets out four things: what the one trial with published adverse event numbers measured, how far the injected record reaches, what the laboratory work raises about a molecule WADA classifies as a growth factor, and why the measurement of this protein in blood is itself unsettled.

Not medical advice

This page reports what has been documented about a compound. It is not medical advice, not a diagnosis, not a dosing protocol, and not a recommendation to obtain or use anything described here. Talk to a licensed clinician about anything concerning your health. Read the full disclaimer.

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What this page reports, and what it does not

We report what has been documented. We do not prescribe what should be done.

Every sentence below reports what a named source measured or searched, in what system, and what it found. Where the answer is that nobody has looked, the page says which study would have looked and names the document recording that it was not done.

This page publishes no dose, no schedule, no route instruction and no list of people who should avoid anything. A list of who should not use a compound is a directions-for-use document, and it only makes sense if the reader is going to use the thing. What replaces it is a description of the compound and its record, written about the molecule rather than about the reader.

One distinction runs through everything here and is worth fixing before the first section. TB-500 is a seven amino acid piece cut out of the middle of this protein and sold under this protein's name. The two are separate substances with separate records, and nothing on this page is a statement about the fragment.

What has been measured

The one trial that published an adverse event count

The Phase 3 trial in neurotrophic keratopathy is the only study of this protein whose adverse event numbers appear in a published paper. Across its 18 participants it reports 16 adverse events in 7 people, 11 of them in the treated group and 5 on placebo, of which one was assessed as related to treatment. One serious adverse event occurred, and it was non-ocular and judged unrelated. No participant withdrew because of an adverse event, and the paper describes most events as ocular and mild [2].

Every part of that is a boundary as well as a finding, and the boundaries are the half that gets dropped. Eighteen people is a small denominator, and a trial stopped early at 18 of a planned 46 was not built to detect an uncommon event in either arm. The exposure was an eye drop over weeks. And the material was a manufactured investigational formulation with a regulatory file behind it, which is a different product from a vial bought under this protein's name. [Human RCT] [2]

How far the injected record reaches

The largest published human exposure to the injected form is the randomised cardiac trial in 96 patients treated after a heart attack, which followed participants to 90 days [1]. The main review covers that trial for its efficacy result, which was null across all 96. It is on this page for a different reason: 90 days in 96 people is the outer edge of published human exposure to this protein by injection.

Past that edge the record holds registrations rather than findings. A Phase 1 intravenous study and a Phase 2 injectable study were both withdrawn before enrolling a single participant [14] [15]. Two Chinese cardiac trials and two healthy-volunteer studies completed, and none of the four has posted results [19] [20] [21] [22]. The studies designed to characterise systemic exposure either did not run or did not report, and those two situations look identical from outside.

One route is missing entirely rather than thinly covered. No registered trial of this protein used the subcutaneous route, which is the route the research-chemical market is built on, so nothing on the public record describes what this protein does by the route it is mostly sold for. [Human RCT] [1]

The growth-factor question the laboratory work raises

WADA classifies this protein as a prohibited growth factor [30], and the laboratory record gives a reason to read that classification as a description rather than as a formality. The 2021 study that identified it as something human muscle releases during exercise reported increased osteoblast proliferation and neurite outgrowth in laboratory systems [3], and the 2016 cardioprotection review sets out its promotion of new blood vessel growth across small and large animal models [6].

Anything that promotes vessel growth and cell proliferation raises a question wherever unwanted tissue might also be growing. That question has not been answered in either direction for this protein: no adequately powered human study has looked, and no animal study designed to look was located for this page. Stating a question is not stating a finding, and the distinction runs both ways here. [Animal] [3] [6]

Measuring the protein at all

A safety question about a circulating protein is usually settled by measuring it, and for this one the measurement is itself unsettled. A 2018 review of the clinical measurement literature found substantial variability in reported healthy-control concentrations both within and between studies, with no standardised protocol [5].

It names three sources of error that any such measurement inherits: platelets left in suspension after centrifugation, release from platelets activated after the sample is drawn, and assay specificity toward post-translational modifications [5]. Anything resting on a measured blood level of this protein carries that uncertainty with it, including any attempt to establish what an administered amount produced in a person. [In-vitro] [5]

What the fragment's record does not answer here

TB-500 is residues 17 to 23 of this protein with an added acetyl group, and it is sold under this protein's name and this protein's trial count. The substitution runs in both directions and neither direction is available.

The adverse event numbers above belong to an eye drop containing the whole 43 amino acid protein. They are not a statement about a seven amino acid fragment, and the fragment's own record does not fill in for the protein either. What TB-500's record holds is set out, with its sources, on the TB-500 safety record, linked under Safety records this page refers to at the foot of this page.

What has not been characterised

Set out plainly, so the shape of the gap is visible rather than implied. No published toxicology package of this protein was located in the literature behind this review: nothing on what a single large exposure does, nothing on daily exposure over weeks or months, nothing on effects on DNA, nothing on pregnancy or offspring, and nothing on whether lifetime exposure produces tumours. That is the result of a search rather than a statement about the world, and it is written as the first of those two things.

The animal work that does exist was built to measure a benefit rather than a harm. The cardiac experiments measured cardiac function, fibrosis and infarct size [1] [6], the hair work compared engineered animals with normal ones [4], and the exercise study measured muscle regeneration and metabolic endpoints [3]. An observation made in passing inside an experiment designed for something else is not a toxicology result, and this page does not convert one into the other.

Nothing published describes exposure beyond 90 days in a person, by any route. Nothing published describes the subcutaneous route in any study. And nothing published describes what is in a vial sold under this name: two molecules share the name in that market, the recombinant preparations used in the trials are not what is sold, and a purity figure does not establish which of the two is present unless the method distinguishes them.

Our takeThe most common error made about this protein's safety record is reading the eye programme as though it covered the injected route. One published trial counted adverse events: 18 people, in an eye, over weeks, using a manufactured ophthalmic formulation. The two registrations that would have produced systematic safety data for an injected form were withdrawn before anyone enrolled, and the completed injected trials elsewhere have posted nothing. The route with the numbers is the one nobody sells.

Talk to a licensed clinician about anything concerning your health.

Frequently asked questions

Is thymosin beta-4 safe?

Nobody can answer that from published evidence, and this site does not answer it from anything else. One published trial reports adverse events for this protein: a Phase 3 eye-drop study that enrolled 18 people and recorded 16 events across 7 of them, one of which was assessed as treatment related [2]. There is no published toxicology package, no study of the subcutaneous route, and nothing describing exposure in a person beyond 90 days.

What side effects were reported in the trials?

The published Phase 3 in neurotrophic keratopathy reports 16 adverse events across 7 of its 18 participants, 11 in the treated group and 5 on placebo, with one assessed as treatment related and one serious event that was non-ocular and judged unrelated. Nobody withdrew because of an adverse event, and the paper describes most events as ocular and mild [2]. That is the whole of the published adverse event record for this protein; the completed injected trials have posted nothing [19] [20] [21] [22].

Does thymosin beta-4 affect the liver or the kidneys?

Nothing published measures either. The study type that collects liver enzymes, kidney markers, organ weights and histology is the repeat-dose toxicity study, and no such study of this protein was located for this page. The human trials measured what they were built to measure: corneal healing in the eye programme [2] and infarct size at 90 days in the cardiac trial [1]. So there is no liver or kidney observation to report in either direction.

Does thymosin beta-4 cause cancer?

No study has tested it, and no carcinogenicity study of this protein was located for this page. There is a question in the neighbourhood and it deserves stating precisely. The protein increased osteoblast proliferation and neurite outgrowth in laboratory systems [3] and promotes new blood vessel growth in animal models [6], and anything that does both raises a question wherever unwanted tissue might also be growing. Nothing published answers that question in either direction, and WADA's classification of the molecule as a growth factor is a rules position rather than a finding about tumours.

Do TB-500's side effects apply to thymosin beta-4?

The two are separate substances and neither record answers for the other. TB-500 is seven amino acids cut out of the middle of this 43 amino acid protein, and it is sold under this protein's name and trial count. What the fragment's record holds is set out, with its sources, on the TB-500 safety record linked at the foot of this page. Nothing on this page describes the fragment, and nothing there describes the protein.

Has long-term use been characterised?

No. The longest published follow-up in a person is 90 days, in the 96 patient cardiac trial [1]. The trials that would have gone further either did not enrol anyone [14] [15] or completed without posting results [19] [20] [21] [22], and no published study of any duration used the subcutaneous route.

What would change what this page says?

Posted results from the four completed injected trials would, and they exist somewhere: two Chinese cardiac studies and two healthy-volunteer studies completed and reported nothing [19] [20] [21] [22]. So would a published toxicology package in any species, since none was located. So would a study of the subcutaneous route, which no registered trial has used.

References

  1. Zhang Y, Dong Q, Bian X, Qiao Z, Cui C, Yang N, Liu J, Fu R, Zhang J, Jia L, Wu C, Guo J, Lin W, Wang J, Fan J, Li Y, Liu F, Yang B, Jia X, Gao C, Bai M, He Y, Han C, Yin D, Dou K. Recombinant human thymosin beta 4 improves ischemic cardiac dysfunction in mice and patients with acute ST-segment elevation myocardial infarction after reperfusion. Cardiovasc Res. 2025. PMID 41229390 DOI 10.1093/cvr/cvaf223
  2. Sosne G, Kleinman HK, Springs C, Gross RH, Sung J, Kang S. 0.1% RGN-259 (Thymosin ß4) Ophthalmic Solution Promotes Healing and Improves Comfort in Neurotrophic Keratopathy Patients in a Randomized, Placebo-Controlled, Double-Masked Phase III Clinical Trial. Int J Mol Sci. 2022. PMID 36613994 DOI 10.3390/ijms24010554
  3. Gonzalez-Franquesa A, Stocks B, Borg ML, Kuefner M, Dalbram E, Nielsen TS, Agrawal A, Pankratova S, Chibalin AV, Karlsson HKR, Gheibi S, Björnholm M, Jørgensen NR, Clemmensen C, Hostrup M, Treebak JT, Krook A, Zierath JR, Deshmukh AS. Discovery of thymosin β4 as a human exerkine and growth factor. Am J Physiol Cell Physiol. 2021. PMID 34495765 DOI 10.1152/ajpcell.00263.2021
  4. Gao X, Liang H, Hou F, Zhang Z, Nuo M, Guo X, Liu D. Thymosin Beta-4 Induces Mouse Hair Growth. PLoS One. 2015. PMID 26083021
  5. Tan WKY, Purnamawati K, Pakkiri LS, Tan SH, Yang X, Chan MY, Drum CL. Sources of variability in quantifying circulating thymosin beta-4: literature review and recommendations. Expert Opin Biol Ther. 2018. PMID 29502471 DOI 10.1080/14712598.2018.1448382
  6. Pipes GT, Yang J. Cardioprotection by Thymosin Beta 4. Vitam Horm. 2016. PMID 27450736 DOI 10.1016/bs.vh.2016.04.004
  7. Hoch K, Volk DE. Structures of Thymosin Proteins. Vitam Horm. 2016. PMID 27450728 DOI 10.1016/bs.vh.2016.04.009
  8. Hannappel E. Thymosin beta4 and its posttranslational modifications. Ann N Y Acad Sci. 2010. PMID 20536447 DOI 10.1111/j.1749-6632.2010.05485.x
  9. Goldstein AL, Hannappel E, Sosne G, Kleinman HK. Thymosin β4: a multi-functional regenerative peptide. Basic properties and clinical applications. Expert Opin Biol Ther. 2012. PMID 22074294 DOI 10.1517/14712598.2012.634793
  10. Sosne G. Thymosin beta 4 and the eye: the journey from bench to bedside. Expert Opin Biol Ther. 2018. PMID 30063853 DOI 10.1080/14712598.2018.1486818 PubMed types this as a Personal Narrative, and the author is also first author on the ReGenTree-funded Phase 3 cited above. Used here for programme history only.
  11. ReGenTree, LLC. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-3. Phase 3, 700 participants actual, completed October 2021. Read through the ClinicalTrials.gov API on 23 August 2026: the record carries no results section. ClinicalTrials.gov. 2019. NCT03937882
  12. ReGenTree, LLC. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome: ARISE-2. Phase 2/3, completed. ClinicalTrials.gov. 2016. NCT02974907
  13. ReGenTree, LLC. Assessment of the Safety and Efficacy of 0.1% RGN-259 Ophthalmic Solution. Phase 3, recruiting as of 23 August 2026. ClinicalTrials.gov. 2022. NCT05555589
  14. RegeneRx Biopharmaceuticals. A Phase 1 Safety Study of the Intravenous Administration of Thymosin Beta 4. Withdrawn before enrolling any participant. ClinicalTrials.gov. 2009. NCT00743769
  15. RegeneRx Biopharmaceuticals. A Study of the Safety and Efficacy of Injectable Thymosin Beta 4. Phase 2, withdrawn before enrolling any participant. ClinicalTrials.gov. 2011. NCT01311518
  16. RegeneRx Biopharmaceuticals. Study of Thymosin Beta 4 in Patients With Pressure Ulcers. Phase 2, completed, no posted results. ClinicalTrials.gov. 2006. NCT00382174
  17. RegeneRx Biopharmaceuticals. Study of Thymosin Beta 4 in Patients With Venous Stasis Ulcers. Phase 2, completed, no posted results. ClinicalTrials.gov. 2009. NCT00832091
  18. RegeneRx Biopharmaceuticals. A Phase 2 Study on Effect of Thymosin Beta 4 on Wound Healing. Terminated. ClinicalTrials.gov. 2006. NCT00311766
  19. Beijing Northland Biotech. Co., Ltd. Safety and Efficacy Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. Phase 2, 62 participants actual, completed, no posted results. Dose arms of 0.25, 0.5 and 2.0 micrograms per kilogram. ClinicalTrials.gov. 2022. NCT05485818
  20. Beijing Northland Biotech. Co., Ltd. Efficacy and Safety Study of Thymosin Beta 4 in Patients With Acute Myocardial Infarction. Phase 2, 90 participants actual, completed, no posted results. Dose arms of 0.5 and 1.0 micrograms per kilogram against placebo. ClinicalTrials.gov. 2023. NCT05984134
  21. Beijing Northland Biotech. Co., Ltd. A Phase 1b Study of Thymosin Beta 4 in Healthy Volunteers. 30 volunteers, completed, no posted results. Single intravenous doses of 0.5, 2.0 and 5.0 micrograms per kilogram. ClinicalTrials.gov. 2020. NCT04555850
  22. Beijing Northland Biotech. Co., Ltd. A Phase 1a Study of Thymosin Beta 4 in Healthy Volunteers. Completed, no posted results. ClinicalTrials.gov. 2020. NCT04555824
  23. Beijing Northland Biotech. Co., Ltd. Recombinant Human Thymosin Beta 4 for Injection (NL005) for Acute Myocardial Infarction. Phase 2c, 189 participants estimated, not yet recruiting as of 23 August 2026. Primary outcome is infarct size on cardiac magnetic resonance at 90 days. ClinicalTrials.gov. 2026. NCT07586865
  24. ReGenTree, LLC. Safety and Efficacy of Thymosin Beta 4 Ophthalmic Solution in Patients With Dry Eye. Phase 2, completed. ClinicalTrials.gov. 2011. NCT01387347
  25. Michigan Cornea Consultants. Comparative Study of Thymosin Beta 4 Eye Drops vs. Vehicle. Phase 2, completed. ClinicalTrials.gov. 2011. NCT01393132
  26. ReGenTree, LLC. A Phase 2 Study of the Safety and Efficacy of Thymosin Beta 4. Terminated. ClinicalTrials.gov. 2008. NCT00598871
  27. ReGenTree, LLC. Assessment of the Safety and Efficacy of RGN-259 Ophthalmic Solutions for Dry Eye Syndrome. Phase 2/3, completed. ClinicalTrials.gov. 2015. NCT02597803
  28. Hudson Biotech. TB-500 (Thymosin Beta 4 17-23 Fragment) in Adults With Stable Atherosclerotic Cardiovascular Disease. Read through the ClinicalTrials.gov API on 23 August 2026: the registered brief summary opens by stating that it is a fictional study and an example of a ClinicalTrials.gov-style record. It is the only registration naming TB-500. ClinicalTrials.gov. 2026. NCT07487363
  29. ReGenTree, LLC. Assessment of the Safety and Efficacy Study of RGN-259 Ophthalmic Solutions for Neurotrophic Keratopathy: SEER-1. Phase 3, terminated, 18 participants actual against 46 planned. This is the registration for the published trial cited above, and it is filed under the drug name RGN-259, which is why a search on the molecule name does not return it. ClinicalTrials.gov. 2015. NCT02600429
  30. World Anti-Doping Agency. The 2026 Prohibited List. Read in full on 23 August 2026. Section S2.3, Growth Factors and Growth Factor Modulators, names Thymosin-ß4 and its derivatives e.g. TB-500. The S2 class heading states that the class is prohibited at all times, in and out of competition, and that all substances in it are non-Specified. World Anti-Doping Agency. 2026. WADA 2026 Prohibited List