A first‐in‐human, randomized, double‐blind, single‐ and multiple‐dose, phase I study of recombinant human thymosin β4 in healthy Chinese volunteers

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 (Cmax) 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.

Progress on the Function and Application of Thymosin β4

“…No doselimiting toxicities or serious adverse events were observed. The tendency of terminal clearance in each dose group was consistent, and there was no obvious accumulation after continuous administration (69). These results were in accordance to those of another phase I clinical trial conducted by Ruff et al, wherein they evaluated the safety, incidence of treatment-emergent adverse events, and pharmacokinetic parameters of synthetic Tb4.…”

Review of the Chinese Landscape in Phase 1 Clinical Trials for Noncancer Innovative Drugs Over 2015 to 2020

“…Sedentary life and increased alcohol consumption indirectly increase the incidence of nonalcoholic fatty liver disease and alcohol‐related liver disease, 30 and drug abuse also increases the risk of drug‐induced liver injury. Moreover, liver disease has been selected as a priority investment area by the National Natural Science Foundation of China, promoting basic and clinical research on drugs for liver disease 28 . Because of this situation, the number of innovative drug projects in the area of the digestive system in China has increased significantly.…”

“…Digestive disease is a common and frequently occurring disease with high recurrence. For a long time, owing to the unique Chinese diet (high fat, high salt, and low fiber) and inadequate health security system, the prevalence rate of digestive diseases in China has remained high worldwide 28 . One of the digestive diseases is viral hepatitis with a high prevalence in China.…”

“…For a long time, owing to the unique Chinese diet (high fat, high salt, and low fiber) and inadequate health security system, the prevalence rate of digestive diseases in China has remained high worldwide. 28 One of the digestive diseases is viral hepatitis with a high prevalence in China. Although hepatitis B prevalence has been controlled and reduced in China since 2005, when the government introduced free hepatitis B vaccination for all newborns, hepatitis C is still prevalent.…”

“…Moreover, liver disease has been selected as a priority investment area by the National Natural Science Foundation of China, promoting basic and clinical research on drugs for liver disease. 28 Because of this situation, the number of innovative drug projects in the area of the digestive system in China has increased significantly.…”