Safety, Pharmacokinetics, and Food Effect of the RORα Agonist TB-840, a Novel Candidate for Metabolic Dysfunction-Associated Steatohepatitis (MASH): A Randomized First-in-Human Study in Healthy Volunteers

Abstract

TB-840 is a novel ROR alpha agonist being developed by Therasid Bioscience Inc. for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). This first-in-human study evaluated the safety, tolerability, pharmacokinetics, and food effect of single ascending doses of TB-840 in healthy adult volunteers. In the single ascending dose part, 64 participants were randomized to receive TB-840 (12.5-200 mg) or placebo. In the food effect part, 6 participants received a single 200 mg dose under fasted and fed conditions in a crossover design. TB-840 was rapidly absorbed (median Tmax 1.7-2.5 h) with a mean half-life of 4.8-9.7 h. Systemic exposure increased dose-proportionally across the studied dose range. A high-fat meal delayed absorption and increased the systemic exposure. TB-840 was well-tolerated, with no serious adverse events reported. These results support the continued development of TB-840 as a potential treatment for MASH. Further studies are warranted to evaluate its efficacy and safety in the target patient population (ClinicalTrials.gov identifier: NCT05045534).