This page shows what was measured, who it was measured in, and what that does not settle.
What TB-500 does in the body
An unapproved fragment sold for injury repair.
Every cell contains a scaffolding protein called actin that it constantly builds and takes apart in order to change shape and move. Thymosin beta-4 is the molecule that holds the spare actin subunits, so it sets how much building material is immediately available. Adding more of it makes cells migrate faster, which is why it speeds up healing of a scratched cornea in the laboratory and why it was developed as an eye drop. The product sold online is not this molecule. It is a seven-amino-acid piece of it, the stretch that grips actin, made by peptide synthesis and sold in a vial. Whether a fragment that short does anything in a person has not been tested.
What happened in people
A purchased product contained a seven-part fragment, not the full natural protein. The parent treatment failed its large study.
✓ Reviewed first-read answer
Where this came from
A person wrote this and a reviewer approved it against this exact record. It carries no effect size.
A reviewer approved this against this record. The reviewed-claim record carrying the exact population and effect size does not exist yet.
No source is stored against this line.
The limit that matters most
No human study has tested it for tendon, ligament or muscle healing.
Where it acts
Cytoplasmic G-actin pool in migrating cells: corneal epithelium, keratinocytes, endothelium, cardiomyocytes
Kind of result
The kind of result is not recorded
Supervision
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
What the registries record it as
The substance registry classes this as protein.
FDA substance registry · QHK6Z47GTG · read 2026-08-29
Where each sentence above came from
No recorded sentence describes the change this makes in a way that stands on its own. The page opens with what it is taken for instead, and the recorded explanation follows below.
Shown as the opening line on this page.
The limit a reviewer approved as the one that matters most here.
The four opening statements run to 145 words.
Words this page uses
Four words worth knowing first
Chosen from what this page shows, with each one explained before the word it depends on.
Placebo
A placebo is a dummy treatment given so the real one can be compared with it.
A picture of it, and where the picture fails
A placebo is like a blank control in an experiment.
Where that stops being true. A blank does nothing. People given a placebo often do get better.
What people get wrong. A placebo effect is read as imaginary. The improvement is measured and real.
An inactive intervention matched in appearance to the test intervention, used to control for non-specific effects.
Comparator
A comparator is whatever the treatment was measured against.
A picture of it, and where the picture fails
It is like the other runner in a race.
Where that stops being true. A race has one winner. A study can show both arms improved.
What people get wrong. Results are read without asking what the other group got. Beating nothing is not beating a treatment.
The control condition against which the experimental intervention is assessed.
Randomisation
Randomisation means chance decides who gets which treatment.
A picture of it, and where the picture fails
It is like a coin toss deciding the groups.
Where that stops being true. A coin toss is fair once. Fairness here comes from doing it for everyone.
What people get wrong. It is thought to make groups identical. It makes them similar on average, including on things nobody measured.
Allocation of participants to arms by a chance process, so that unmeasured factors are balanced in expectation.
What happened in people◇Read from sources, not yet reviewed
What happened in people
Each card is one study: the exact question it asked, who was in it, and whether it showed what it set out to show.
Co-primary: change from baseline at day 29 in ocular discomfort and in corneal fluorescein staining
Ocular discomfort change +0.07 on RGN-259 versus -0.04 on placebo; corneal fluorescein staining change +0.07 versus -0.01. Lower is better on both scales, so both co-primaries favoured placebo
Repeated elsewhere
Failed to Replicate
What this does not prove. A study that did not show an effect does not show that no effect exists anywhere.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Ophthalmic solution 0.1% and intravenous infusion in trials; lyophilised powder for subcutaneous injection outside them
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Ocular discomfort and corneal fluorescein staining
✓ The study showed what it set out to show
Who was studied
NCT01393132 (phase 2 in severe dry eye)
How many people
9
Study design
Phase 2, randomised double-masked placebo-controlled, 56 days
Compared against
A dummy treatment
Kind of result
A number that stands in for health
What was found
35.1% reduction in ocular discomfort versus vehicle at day 56 (P = 0.0141) and 59.1% reduction in total corneal fluorescein staining (P = 0.0108), analysed as 12 treated eyes against 6 control eyes
Repeated elsewhere
Failed to Replicate
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Ophthalmic solution 0.1% and intravenous infusion in trials; lyophilised powder for subcutaneous injection outside them
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
Safety, tolerability, pharmacokinetics and anti-drug antibodies in healthy volunteers
✓ The study showed what it set out to show
Who was studied
Wang 2021 first-in-human phase 1 of recombinant thymosin beta-4 (NL005)
How many people
84
Study design
Phase 1, randomised double-blind, single and multiple ascending intravenous doses
Compared against
Not recorded for this study
Kind of result
A number that stands in for health
What was found
Adverse events mild to moderate; no dose-limiting toxicity and no serious adverse events across 0.05 to 25.0 ug/kg single doses and 0.5 to 5.0 ug/kg daily for 10 days; dose-proportional Cmax and AUC with no accumulation
Repeated elsewhere
Unreplicated
What this does not prove. Meeting one endpoint in one population does not carry to other goals or other people.
The limits of this study, and where it came from
Main limit. No limitation is recorded for this study.
How far it carries. This study is recorded from the curated record, not from the registry match.
Form and route. Ophthalmic solution 0.1% and intravenous infusion in trials; lyophilised powder for subcutaneous injection outside them
Interval reported. Not recorded in this summary
Written into the record, not signed off as a reviewed claim.
RNAWiki holds 4 written-up human studies for this substance, each with the question it asked.
How we know it
Each card names the study, the number of people and what the study set out to measure.
What this does not prove
These summaries were written by a person and have not been signed off as reviewed claims.
Why it matters
A study that failed is as informative as one that worked, and both are here.
What we still do not know
No reviewed claim exists, so no exact population, effect size or interval is published yet.
What happened in people◇Read from sources, not yet reviewed
How close this is to real life
The top step is something a person would feel or care about. The bottom is a guess from software. Filled steps are where evidence exists for this substance.
□Living longer, or avoiding a major eventNo evidence recorded. Death, a heart attack, a stroke, a hospital stay.No registered study measures this.
□What a body can do day to dayNo evidence recorded. Walking, dressing, breathing, recovering.No registered study measures this.
□Measured performanceNo evidence recorded. How much was lifted, how far was run, how fast.No registered study measures this.
□Symptoms and quality of lifeNo evidence recorded. Pain, tiredness, mood, sleep, as the person rated it.No registered study measures this.
□A number that stands in for healthNo evidence recorded. Cholesterol, blood sugar, bone density. A stand-in, not the thing itself.No registered study measures this.
■A step measured inside a personEvidence recorded. Something measured in human tissue or human cells.A human record sits on the stored organism ladder.
□AnimalsNo evidence recorded. Mice, rats, dogs. Useful for ideas, not proof about people.No animal record is stored.
□Cells in a dishNo evidence recorded. Cells or chemistry on a bench, far from a whole body.No cell or bench record is stored.
□A guess from softwareNo evidence recorded. Nobody measured it. RNAWiki never publishes one as a finding.RNAWiki stores no prediction for this record. Software can suggest a link. RNAWiki does not publish one as a finding.
Higher on these steps means closer to something a person would feel. It does not mean better done.
What it changes in the body◇Read from sources, not yet reviewed
The path through the body
From what a person takes to what changes. A solid line is a step measured in people. A dashed line is a step nobody has measured that way.
Start
TB-500
What a person takes: Ophthalmic solution 0.1% and intravenous infusion in trials; lyophilised powder for subcutaneous injection outside them.
The measurement behind this step
The tested formulations are an eye drop used six times daily and an intravenous recombinant preparation dosed in micrograms per kilogram. What is sold is a lyophilised vial of synthetic Ac-LKKTETQ for reconstitution with bacteriostatic water and subcutaneous injection, typically in milligram quantities. No pharmacokinetic study exists for that route, that molecule, or that dose range.
Getting in
Given as drops, as an infusion, or by subcutaneous injection
The tested routes are eye drops and a drip into a vein. The route people actually use is a needle under the skin.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
RGN-259 is a 0.1% ophthalmic solution used six times daily; NL005 is an intravenous recombinant preparation dosed in micrograms per kilogram. TB-500 is sold as a lyophilised powder for reconstitution and subcutaneous or intramuscular injection, a route for which no pharmacokinetic data exist for either the peptide or the fragment.
There is no lock on the cell surface for this molecule to fit. It has to get inside, where its target is.
╌╌Measured in animals. A result in animals says what to test next. It does not say what happens in people.
The measurement behind this step
Thymosin beta-4 has no identified classical cell-surface receptor. It is small, highly charged and intrinsically disordered, and its target — monomeric actin — is cytoplasmic. Internalisation is one of the least well characterised steps in its pharmacology and the point at which extrapolation from in vitro results to an injected dose is weakest.
It clamps onto a loose actin building block so that block cannot be added to the growing scaffold.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
The central helix and the LKKTETQ motif at residues 17-23 form a 1:1 complex with ATP-G-actin, occluding the surfaces used for nucleotide exchange and for addition to the barbed end. The intracellular pool of thymosin beta-4 is what sets how much polymerisation-competent actin a cell holds in reserve. Ac-LKKTETQ is that motif in isolation.
With a bigger reserve of building blocks, cells can take apart and rebuild their internal scaffolding quickly, which is what crawling into a wound requires.
╌╌Described, with no measurement named. No measurement is named for this step, so it is drawn as an unconfirmed link.
The measurement behind this step
Raising available sequestered monomer accelerates the treadmilling cycle that drives lamellipodial protrusion. In corneal epithelial and dermal models this shows up as faster scratch-wound closure, reduced inflammatory cytokine expression and reduced apoptosis. These are the measurements behind the ophthalmic development programme.
A convincing small trial, a null large one, no approval
A nine-patient study looked strong. A 601-patient study of the same drops came out slightly behind placebo on both main measures. Nothing containing this molecule is approved anywhere.
──Measured in people. Written by a person from the study named beside the step. Not signed off as a reviewed claim.
The measurement behind this step
ARISE-2 posted change-from-baseline at day 29 of +0.07 on drug versus -0.04 on placebo for ocular discomfort, and +0.07 versus -0.01 for corneal fluorescein staining. Development continues in neurotrophic keratopathy. No thymosin beta-4 product holds a marketing authorisation in any jurisdiction, and the fragment sold as TB-500 has never entered a human trial.
No suggested links are held for this record, so nothing is hidden from this path.
What we know
The record describes 5 steps from taking it to an effect in a person.
How we know it
Each step names the study behind it in the technical detail beside it.
What this does not prove
A change inside the body is a reason to look. It is not a result in a person.
Why it matters
A reader can see exactly where the chain stops being measured in people.
What we still do not know
No reviewed claim binds any of these steps to a named population.
What is missing or unclear◇Read from sources, not yet reviewed
Were people like you studied?
RNAWiki cannot tell whether a study fits you. It can show who was in it, and where the result stops carrying.
Who was studied
People similar to this profile were included.
In trials: patients with dry eye, neurotrophic keratopathy, pressure and venous ulcers, and acute myocardial infarction. Outside trials: people with tendon, ligament and muscle injuries, and horses, where doping-control methods for TB-500 were developed first.
Who is missing from the studies
Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
Where the result stopped carrying
ARISE-2 missed both co-primary endpoints with the active arm numerically worse than placebo on each
The neurotrophic keratopathy phase 3 RGN-NK-301 (NCT02600429) was terminated after 18 patients for a stated business decision
A phase 2 of injectable thymosin beta-4 for chronic wounds (NCT01311518) was withdrawn before enrolling a single participant
This is a scope explorer, not a diagnosis engine.
It shows who was studied so you can see whether people similar to you were included.
RNAWiki cannot tell whether a study fits you. It can show who was in it.
What it would be like to take◇Read from sources, not yet reviewed
Why it might seem to do nothing
A real effect and a noticed effect are different things. These are the recorded reasons the two come apart.
It was studied for a different goal
The studies measured something else entirely.
On this record: Some registered studies measured things that match no goal on this page.
It was studied in different people
The people in the studies were not much like the reader.
On this record: Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
The evidence may simply be wrong
Small early studies often do not hold up.
On this record: RNAWiki has not yet published a reviewed conclusion for this use.
Other reasons RNAWiki checked and found nothing for (10)
A different form was studied
The studied form is not the form on the shelf. Nothing in this record points to this reason.
There was nothing to correct
Where a level is already normal, topping it up may change nothing. Nothing in this record points to this reason.
Something else had to happen too
In the studies it was paired with training, a diet or another treatment. Nothing in this record points to this reason.
The change is too small to feel
A real change can still sit below what a person notices. Nothing in this record points to this reason.
Day-to-day swing hides it
Sleep, food, stress and time of day move most numbers more than this would. Nothing in this record points to this reason.
Not enough time yet
The studies ran longer than the person has waited. Nothing in this record points to this reason.
It was not taken as studied
Missed days change the result, and studies count them. Nothing in this record points to this reason.
Something else changed at the same time
Two changes at once cannot be told apart afterwards. Nothing in this record points to this reason.
The product may not be what it says
Contents of a sold product are not always what the label states. Nothing in this record points to this reason.
No recorded reason
RNAWiki has nothing stored that would explain it. Nothing in this record points to this reason.
None of these is a reason to take more. Taking more is not a step this page ever suggests.
What it would be like to take◇Read from sources, not yet reviewed
What taking it involves
The recorded facts about getting hold of it and using it. Nothing here is a suggestion about what you should do.
How it is supplied
Still being tested
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
Read from the recorded approval status.
No source is stored against this line.
Form and route
Ophthalmic solution 0.1% and intravenous infusion in trials; lyophilised powder for subcutaneous injection outside them
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form and route recorded on this substance.
No source is stored against this line.
Who oversees it
Professional supervision is normally required. It is a prescription or clinician-administered medicine where it is approved.
❝ Quoted from a source
Where this came from
Copied from a source RNAWiki stored, with the source named.
The identity record classes it as investigational; no register records an approval.
No source is stored against this line.
What is in the pack
The tested formulations are an eye drop used six times daily and an intravenous recombinant preparation dosed in micrograms per kilogram. What is sold is a lyophilised vial of synthetic Ac-LKKTETQ for reconstitution with bacteriostatic water and subcutaneous injection, typically in milligram quantities. No pharmacokinetic study exists for that route, that molecule, or that dose range.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on how this is sold and what that means for what is in the pack.
No source is stored against this line.
Where it is registered
Regulatory records are listed in the technical disclosure at the foot of this page.
# Counted from records
Where this came from
A count of rows RNAWiki holds. It describes our records, not your body.
Register entries are stored per jurisdiction and shown with their dates.
No source is stored against this line.
Why people stop
Not recorded.
∅ Nothing recorded
Where this came from
RNAWiki holds nothing here and says so rather than guessing.
No record of why people stopped taking it is stored for this substance.
No source is stored against this line.
What it would be like to take◇Read from sources, not yet reviewed
What can go wrong
Sorted by where each line came from. A regulator's label and a report somebody sent in are not the same kind of fact.
·Worth asking a clinician aboutWritten into the record from the studies named on this page
The full peptide was well tolerated as eye drops across a phase 2 and phase 3 programme and intravenously in 84 healthy volunteers, with no serious adverse events and no dose-limiting toxicity up to 25 micrograms per kilogram. Nothing is known about the safety of the seven-residue fragment in humans at any dose, because it has never been studied in a person. The general concerns applying to any unlicensed injectable peptide — endotoxin, deletion sequences, sterility, immunogenicity — apply here and are not addressed by the trial data on the parent molecule.
Nobody counted how many people took this and were fine, so this cannot be turned into a rate.
Over a long time. No completed tested study window is recorded, so long-term effects are not established by the registry record.
Groups the studies covered thinly. Which groups were under-represented in the studies has not been recorded for this substance. Pregnancy, breastfeeding, children, older adults, and people with liver or kidney conditions are commonly excluded from trials; nothing here says whether they were.
What is missing or unclear◇Read from sources, not yet reviewed
Does the exact form matter?
Evidence belongs to the exact thing that was tested. A different salt, a different mixture or a different preparation is a different question.
The form that was studied
Ophthalmic solution 0.1% and intravenous infusion in trials; lyophilised powder for subcutaneous injection outside them
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
The form used in the studies cited on this page.
No source is stored against this line.
What is sold
What is sold is a lyophilised vial of synthetic Ac-LKKTETQ for reconstitution with bacteriostatic water and subcutaneous injection, typically in milligram quantities. No pharmacokinetic study exists for that route, that molecule, or that dose range.
✎ Source-linked record
Where this came from
A person wrote this into the record with the study named beside it. No reviewer has signed it off.
Recorded notes on which forms are sold and how they compare.
No source is stored against this line.
What is recorded as being sold
9 products list this as an active ingredient in the United States drug directory. 9 of them contain it and nothing else.
FDA National Drug Code directory · 73212-117 · read 2026-08-29
They are sold as powder.
FDA National Drug Code directory · 73212-117 · read 2026-08-29
Evidence carries across two names for one substance. It does not carry across a salt, a mirror form or a mixture.
What it would be like to take◇Read from sources, not yet reviewed
What you could measure
This one is decided with a clinician, so this section holds questions to ask rather than a plan to run.
Self-experiment planning is not offered for a prescription or clinician-supervised medicine, investigational agent. The questions below are for a clinician or pharmacist.
Questions worth asking
Which of the trials of TB-500 studied people like me?
What was measured, and for how long?
Was the result a laboratory value or a health outcome?
What would we watch for, and when would we stop?
Tracking can show whether something changed for you. It cannot show what caused it.
RNAWiki records evidence. It does not say whether this substance is right for you.
What is missing or unclear◇Read from sources, not yet reviewed
Claims that go past the evidence
Things said about this substance that sound reasonable, and the exact step that is missing between the evidence and the claim.
✗Goes past the evidence
That results obtained with the 43-residue peptide describe the 7-residue fragment that is actually sold
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That TB-500 accelerates tendon, ligament or muscle healing in people, which no trial has tested in any species-appropriate human design
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That an intravenous microgram-per-kilogram safety dataset covers milligram subcutaneous self-injection of a different molecule
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
✗Goes past the evidence
That a positive small ophthalmic trial predicted the large one, when the 601-patient replication came out numerically behind placebo
Why it sounds right. It follows from something real on this page: a body step, an animal result or a related finding.
The missing step. Nobody measured this in people for this use, or the study that did measure it did not show it.
What would change this
A study in people, for this exact use, measuring this exact thing, that a reviewer signs off.
RNAWiki has not yet published a reviewed conclusion for this use.
What is missing or unclear◇Read from sources, not yet reviewed
What nobody knows yet
Open questions, each with why it is open and what would close it.
How much did people take in the studies?
The sources RNAWiki checked hold nothing for this field.
Why it matters. A result belongs to an amount. Without the amount the result floats free.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
How fast does the body clear it?
The sources RNAWiki checked hold nothing for this field.
Why it matters. Without this, nothing on this page can say how long anything lasts.
What would answer it
A stored source that records it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing populations
Which groups were under-represented in the studies has not been recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing long-term data
No completed tested study window is recorded.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
No reviewed conclusion
RNAWiki has not yet published a reviewed conclusion for this use.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Missing interaction studies
No interaction was found in the registers checked. Not finding one is not the same as showing there is none.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Formulation uncertainty
Several salts, forms or products of TB-500 are recorded. Results from one form may not transfer to another.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
Mechanism not reviewed
No reviewed mechanism story exists for this substance.
Why it matters. Recorded by the evidence model as a gap on this record.
What would answer it
A study that measures it, and a reviewer to sign it off.
Last checked 2026-09-04. Searched: The sources listed in the receipts at the foot of this page.
What happened in people◇Read from sources, not yet reviewed
Check any of this yourself
Every line above traced back to the study it came from. This is the technical layer, and the vocabulary changes here.
Every line above can be traced to the study named beside it. Follow the link and read it.
The product sold as TB-500 is a seven-residue fragment, not the peptide
In plain words
A doping control laboratory bought a TB-500 product and identified what was in it: a seven-amino-acid piece of thymosin beta-4 with an acetyl cap, not the whole 43-residue molecule.
What was measured
Identity of the active species in a commercially sold TB-500 formulation by high-resolution mass spectrometry
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Esposito et al. at the Ghent doping control laboratory analysed the formulation TB-500 by high-performance liquid chromatography with high-resolution mass spectrometry on an Orbitrap Exactive and identified the N-terminally acetylated 17-23 fragment of human thymosin beta-4, Ac-LKKTETQ. They then synthesised Ac-LKKTETQ by solid-phase peptide synthesis to confirm the identification and proposed a triple-quadrupole method for detecting it in plasma and urine. This is the single most important fact on the page: the clinical literature on thymosin beta-4 is about a 4,963-dalton peptide and the product is an 889-dalton fragment of it. Read that clinical literature as evidence about TB-500 and you are attributing to a fragment the results obtained with the whole molecule.
Written into the record, not signed off as a reviewed claim
ARISE-2 missed both co-primary endpoints, numerically behind placebo
In plain words
The 601-patient phase 3 trial of thymosin beta-4 eye drops for dry eye posted its results. On both main measures the drug group did slightly worse than placebo.
What was measured
Change from baseline at day 29 in ocular discomfort and corneal fluorescein staining, RGN-259 0.1% versus placebo
Effect estimate
No reviewed effect estimate exists for this record.
Limits
This entry records a failure.
From the source
ARISE-2 (NCT02974907) was a multicentre, randomised, double-masked, placebo-controlled phase 3 study of 0.1% RGN-259 ophthalmic solution in 601 patients with dry eye, completed March 2018, with two co-primary endpoints at day 29: ocular discomfort on the Ora Calibra 6-point scale and corneal fluorescein staining on the Ora Calibra 5-point scale, both as change from baseline. The posted results give ocular discomfort change of +0.07 on RGN-259 against -0.04 on placebo, and corneal fluorescein staining change of +0.07 on RGN-259 against -0.01 on placebo. On these scales a lower score is better and a negative change is improvement, so both co-primary endpoints favoured placebo numerically. A trial with co-primary endpoints that misses both is a failed trial.
Source
ClinicalTrials.gov posted results, NCT02974907 (ARISE-2), primary outcome measures at day 29
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
verified
Review state
Written into the record, not signed off as a reviewed claim
The small phase 2 in severe dry eye did separate from placebo
In plain words
A nine-patient trial found meaningful improvements in eye discomfort and corneal damage on the drops, which is what justified taking it into phase 3.
What was measured
Percentage reduction in ocular discomfort and total corneal fluorescein staining at day 56 versus vehicle
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Sosne et al. ran a small multicentre randomised double-masked placebo-controlled 56-day phase 2 trial (NCT01393132) at two US sites, treating nine patients with severe dry eye, including disease associated with graft-versus-host disease, with 0.1% RGN-259 or vehicle six times daily for 28 days. At day 56 the RGN-259 group (12 eyes) had a 35.1% reduction in ocular discomfort against vehicle (6 eyes), P = 0.0141, and a 59.1% reduction in total corneal fluorescein staining, P = 0.0108, with improvements also in tear film break-up time and tear volume. The trial was safe and well tolerated. It is also nine patients, unblinded to nothing but analysed as eyes, and its effect sizes did not survive into a 601-patient replication. That sequence — a striking small trial followed by a null large one — is the most common shape in this entire file.
Written into the record, not signed off as a reviewed claim
Intravenous recombinant thymosin beta-4 was tolerated in 84 healthy volunteers
In plain words
A first-in-human study gave recombinant thymosin beta-4 by vein to 84 healthy Chinese volunteers across single and repeated doses with no serious adverse events.
What was measured
Adverse events, Cmax, AUC and anti-drug antibodies across seven single-dose and three multiple-dose cohorts
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Wang et al. ran a randomised, double-blind, placebo-controlled phase 1 of recombinant human thymosin beta-4 (NL005). Seven cohorts totalling 54 subjects received single intravenous doses of 0.05, 0.25, 0.5, 2.0, 5.0, 12.5 or 25.0 micrograms per kilogram and were observed for 28 days. A further 30 subjects in three cohorts received 0.5, 2.0 or 5.0 micrograms per kilogram once daily for 10 days with 28-day observation. Adverse events were mild to moderate, with no dose-limiting toxicities and no serious adverse events. Cmax and AUC rose with dose, terminal clearance was consistent across cohorts, and there was no accumulation on repeated dosing. This is the only systematic human safety and pharmacokinetic dataset for the molecule, it used the full recombinant peptide intravenously, and the doses are in micrograms per kilogram.
Written into the record, not signed off as a reviewed claim
Tendon and ligament repair is the selling point and has no human data
In plain words
TB-500 is sold for healing tendons, ligaments and muscle. No human trial has ever tested it for any of those.
What was measured
That TB-500 accelerates tendon, ligament or muscle repair in humans — the entire basis on which it is sold, with no human trial of the compound for those tissues
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
The registered human programme for thymosin beta-4 covers ophthalmic surface disease (dry eye, neurotrophic keratopathy), chronic skin wounds (pressure ulcers NCT00382174 n=72, venous stasis ulcers NCT00832091 n=72, epidermolysis bullosa NCT00311766 terminated at n=30), and cardiac indications (acute myocardial infarction, phase 1 and 2). There is no registered trial of thymosin beta-4 or of Ac-LKKTETQ for tendon, ligament, muscle or joint injury in humans. The tendon claim rests on rodent and equine work and on the actin-sequestration mechanism, which is a plausible mechanism and not a result. The injectable formulation studied in a phase 2 for chronic wounds, NCT01311518, was withdrawn before enrolling anybody.
Source
ClinicalTrials.gov registrations for thymosin beta-4: NCT00382174, NCT00832091, NCT00311766, NCT01311518, NCT05984134; no registered trial exists for tendon, ligament or muscle injury
Role in the trial
Not matched to a registered study
Identity check
no open identity hold
Audit mark
caution
Review state
Written into the record, not signed off as a reviewed claim
Detection methods for TB-500 were written for racehorses first
In plain words
The first published method for finding TB-500 in a body was developed for equine urine and plasma, because it reached horse racing before it reached human sport.
What was measured
Analytical detection of TB-500 and Ac-LKKTETQ in equine urine and plasma and in human plasma and urine
Effect estimate
No reviewed effect estimate exists for this record.
Limits
See the technical detail.
From the source
Ho et al. published a liquid chromatography-mass spectrometry method for the doping control analysis of TB-500 in equine urine and plasma, describing it explicitly as a synthetic version of an active region of thymosin beta-4. The Ghent group followed with a plasma and urine strategy for human samples. Thymosin beta-4 and its fragments are prohibited at all times in human sport under WADA class S2, growth factors and related substances. The analytical problem is that thymosin beta-4 is endogenous and abundant, so a confirmation for the parent peptide is difficult, while the seven-residue fragment is not endogenous and its presence is unambiguous — which means the grey-market product is easier to detect than the real drug would be.
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What is not here
6 questions this page could not answer
These sections were prepared and left out because there was nothing to put in them. They are listed rather than hidden, so the gaps in this record are visible.
What was measured, goal by goal — found nothing in the sources checked.
Felt, measured, or meaningful — found nothing in the sources checked.
How long anything takes — found nothing in the sources checked.
What it may clash with — found nothing in the sources checked.
Other ways to the same goal — found nothing in the sources checked.
What changed on this page — found nothing in the sources checked.
The record as stored
The full record, for auditing
Everything above is built from what is below. This layer keeps the technical vocabulary, record identifiers and every stored row, so a reader who wants to check the page can.
The older medicine-wide conclusion held in this record
Written for a clinical reader, and about the medicine as a whole rather than about one indication, population and set of trials. RNAWiki does not treat it as a programme conclusion and no reviewer has signed it off in that form. It is here word for word because it is what the record holds.
The full peptide is real, well characterised and in phase 3; the product sold as TB-500 is its seven-residue fragment Ac-LKKTETQ, which has never been given to a human in a trial, and the largest completed phase 3 of the parent molecule missed both co-primary endpoints with the drug arm numerically worse than placebo.
Recorded evidence blocks (5)
Q1
What did TB-500's largest trial (80 people) and its longest (2 years) measure?
80 people in TB-500's largest registered study, 2 years in its longest registered window, measuring incidence of treatment-emergent adverse events (TEAEs). ClinicalTrials.gov · 2026-09-01
1 phase1, 1 phase2; NCT07487363; 2028-02-17; no ageing endpoint recorded
These counts include studies where TB-500 was a comparison treatment, a background treatment or an exposure in an observational study, and the longest window may be a planned end date. Trial roles have not yet been classified for this record.
Show the evidence
phase1
1
phase2
1
recorded 2026-09-01 · last checked 2026-09-04
Q2
TB-500 was tested only in human — what did it show?
Sold as TB-500. The full peptide is thymosin beta-4, developed as RGN-259 (eye drops) and NL005 (recombinant injection)
Also called
N-Acetyl-L-leucyl-L-lysyl-L-lysyl-L-threonyl-L-α-glutamyl-L-threonyl-L-glutamine, N-Acetyl-Leu-Lys-Lys-Thr-Glu-Thr-Gln, N-terminal acetylated 17-23 fragment of thymosin beta 4
Development code
TB500
Component
TB-500 (thymosin beta-4)
Sources (3)
Sources
ClinicalTrials.govClinicalTrials.gov API v2 snapshot 2026-09-01T09:00:05 ·
ClinicalTrials.gov — US Government work · Europe PMC — metadata only, under the recorded legal gate · derived from this page's own recorded fields; no external licence
✗ required summary fields resolved: 4 required field(s) not terminal: Why people use it, Best-supported result, Biggest unanswered question, Human evidence
✓ public claims reviewed: 0 reviewed claim(s); drafts are never rendered
✓ source coverage passed: 3 source rows
✓ no critical contamination: no quarantine open
✓ canonical metadata passed: slug and display name present
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