A randomized, placebo-controlled, single and multiple dose study of intravenous thymosin beta4 in healthy volunteers
Ruff D, Crockford D, Girardi G, Zhang Y
Annals of the New York Academy of Sciences (2010) · n=40
The Phase 1 human-safety paper that gated everything downstream: 40 healthy volunteers received IV thymosin β4 at 42, 140, 420, or 1260 mg single doses then daily for 14 days, with no dose-limiting toxicities, no serious adverse events, and a dose-proportional PK profile.
This is the foundational Phase 1 human-safety paper for synthetic thymosin β4 — the gating clinical study that the RegeneRx-led acute myocardial infarction and ophthalmic programs were built on. Ruff and colleagues conducted a randomized, placebo-controlled, ascending-dose Phase 1 trial in 40 healthy volunteers across four cohorts of 10 subjects each. The dosing scheme combined a single intravenous dose (42, 140, 420, or 1260 mg) with subsequent daily dosing at the same level for 14 days.
The single-dose pharmacokinetic profile was dose-proportional, with an increasing half-life at higher doses — consistent with extended tissue distribution at the higher exposures. Adverse events were infrequent and uniformly mild-to-moderate in intensity. There were no dose-limiting toxicities and no serious adverse events across the full dose range, including the supraphysiologic 1260 mg cohort. The authors concluded that synthetic intravenous thymosin β4 was well tolerated and supported continued clinical development for the molecule's framed indications: acute myocardial infarction (RGN-352), dry eye disease (RGN-259), and wound healing.
The paper's relevance for today's "TB-500" research-peptide market is indirect but important — this is the only published human IV-dosing safety dataset for the full-length 43-amino-acid thymosin β4 molecule. Most subcutaneous self-administered use in the off-label market falls outside the dose range and route studied here.
This is a Phase 1 trial in healthy volunteers — its purpose is safety and pharmacokinetics, not efficacy. Nothing in this paper tests whether thymosin β4 does anything therapeutically. The 40-subject sample size is standard for Phase 1 but small for rare-event detection — a Phase 1 cannot rule out adverse events at the 1-in-100 or rarer frequencies that matter for long-tail chronic use. The dosing was intravenous, not subcutaneous, and limited to 14 days; the chronic SC dosing that defines the "TB-500" off-label market is a different exposure profile not studied here.
The "TB-500" sold in research-peptide channels is sometimes claimed to be a synthetic 17-amino-acid fragment of thymosin β4 (the so-called "active region") rather than the full 43-residue molecule used in this trial. The safety data here do not transfer to that fragment, and the fragment has no published human safety dataset of comparable rigor. Industry sponsorship by RegeneRx is disclosed.
07·Member discussion
No member discussion yet.
Member-only conversation lives here — cycle notes, practitioner commentary, pattern-matching. Be the first paying member to start the thread.