HIGHTIDE-B (02511) has announced the completion of a global multicenter Phase IIb clinical study of HTD1801 in patients with metabolic dysfunction-associated steatohepatitis (MASH). The CENTRICITY trial (NCT05623189) was a randomized, double-blind, placebo-controlled global multicenter Phase IIb clinical trial involving 218 patients, designed to evaluate the efficacy and safety of HTD1801 compared to a placebo in MASH patients who also had type 2 diabetes (T2DM) or prediabetes.

Preliminary analysis results indicated that 48% of patients in the placebo group achieved a reduction of ≥2 points in the non-alcoholic fatty liver disease activity score (NAS) without worsening of fibrosis, or achieved MASH resolution without worsening of fibrosis after the treatment period. This result was significantly higher than the placebo effects observed in previous similar clinical studies. A meta-analysis published in 2025, which covered 127 MASH clinical trials involving 78 different investigational drugs, reported that trials with designs similar to this study typically showed placebo response rates not exceeding 20%.

Following an investigation by a third-party organization to further review the study's conduct, issues related to study execution and quality management were identified. These included management of concomitant medications, where a significantly higher number of patients in the placebo group improperly initiated or intensified GLP-1RA therapy in violation of the protocol, and issues with patient compliance. These factors may have significantly influenced the trial outcomes.

Based on these findings, the company conducted a post-hoc analysis of the study data. After excluding confounding factors such as protocol-violating medication use, the placebo effect decreased noticeably, and HTD1801 showed a trend toward therapeutic improvement over the placebo across multiple liver histology indicators. The results of this post-hoc analysis further suggest that the study was affected and confounded by several operational and quality management factors.

The long-term safety and tolerability profile of HTD1801 observed in this study were consistent with results from previous clinical trials. Given that HTD1801 successfully met primary endpoints in a prior Phase IIa study in MASH patients with T2DM, as well as in three completed Phase III clinical trials in a T2DM patient population—demonstrating multiple benefits and advancing smoothly toward a New Drug Application (NDA)—HIGHTIDE will conduct a further evaluation of HTD1801's clinical development strategy for the MASH indication. This evaluation will integrate the overall data, review findings, and post-hoc analysis conclusions from this recent study. The company will also communicate with the U.S. Food and Drug Administration (FDA) and perform a comprehensive assessment based on regulatory feedback to determine the subsequent development plan.