First-in-human Phase I clinical trial of recombinant human thymosin β4 (NL005) via intravenous injection in 54 healthy Chinese volunteers across 7 ascending dose cohorts (0.05–25 μg/kg, single and multiple doses). NL005 was well-tolerated at all doses with no dose-limiting toxicities. Pharmacokinetics showed dose-proportional exposure. Anti-drug antibody formation was assessed. Establishes the safety, tolerability, and PK profile of IV rhTβ4 in humans—foundational data for therapeutic development.
Abstract
The study evaluated the safety, tolerability, pharmacokinetics (PK) and anti-drug antibody (ADA) of the recombinant human thymosin β4 (NL005) for single and multiple intravenous injections in healthy subjects. Seven cohorts, with 54 healthy subjects, were given a single intravenous dose of NL005 or placebo and were observed for 28 days. The cohorts received ascending doses of either 0.05, 0.25, 0.5, 2.0, 5.0, 12.5 or 25.0 μg/kg in the single-dose trial. A total of 30 healthy subjects were randomly enrolled in the multiple-dose trial, and 3 cohorts (0.5, 2.0 and 5.0 μg/kg) were administered once human thymosin β4 daily for 10 days and observed for 28 days. The adverse events were mild to moderate in intensity. There were no dose-limiting toxicities or serious adverse events. The plasma concentration, maximum peak concentration (C) and AUC of each dose group increased with the increase in the dose. The tendency of terminal clearance in each dose group was consistent, and there was no obvious accumulation after continuous administration. Thus, the drug can be concluded to be well tolerated and safe in healthy people and suitable for use in a clinical study for the treatment of acute myocardial infarction.
adverse eventanti-drug antibodyintravenousmyocardial infarctionpharmacokineticsrecombinant human thymosin β4safetyterminal clearancetolerability
A first-in-human, randomized, double-blind, single- and multiple-dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers. | Pepdox