NeuroBo Pharmaceuticals, Inc. has announced the completion of the last patient last visit in its Phase 2a clinical trial assessing DA-1241 for the treatment of metabolic dysfunction-associated steatohepatitis (MASH). The trial is a two-part study evaluating the efficacy and safety of DA-1241, a novel G-Protein-Coupled Receptor 119 (GPR119) agonist. Topline data from both parts of the Phase 2a trial are expected in December 2024.
Trial Design and Objectives
The Phase 2a trial consists of two parts. Part 1 explores DA-1241 compared to placebo, while Part 2 investigates the efficacy of DA-1241 in combination with sitagliptin, a DPP-4 inhibitor. NeuroBo believes the combination will demonstrate synergistic effects compared to DA-1241 alone. The trial design for both parts is a 16-week, multicenter, randomized, double-blind, placebo-controlled, parallel clinical study.
A total of 109 patients were randomized, with 95 completing the dosing. In Part 1, patients were randomized in a 1:2:1 ratio into three treatment groups: DA-1241 50 mg, DA-1241 100 mg, or placebo. In Part 2, patients were randomized in a 2:1 ratio into two treatment groups: DA-1241 100 mg/sitagliptin 100 mg or placebo.
Endpoints and Safety Measures
The primary endpoint for both Part 1 and Part 2 is the change from baseline in alanine transaminase (ALT) levels at Week 16. Secondary efficacy endpoints include the proportion of subjects with normalization of ALT and absolute changes in total cholesterol, low and high-density lipoprotein cholesterol, triglycerides, and free fatty acids from baseline. Safety will be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs) leading to discontinuation, as well as laboratory abnormalities.
DA-1241: Mechanism of Action
DA-1241 is a novel G-Protein-Coupled Receptor 119 (GPR119) agonist with potential as a standalone or combination therapy for both MASH and type 2 diabetes (T2D). As a GPR119 agonist, DA-1241 promotes the release of key gut peptides GLP-1, GIP, and PYY, which play a role in glucose and lipid metabolism, as well as weight loss. Pre-clinical studies have demonstrated that DA-1241 has beneficial effects on glucose and lipid profiles, as well as liver inflammation. In Phase 1a and 1b trials, DA-1241 was well tolerated in both healthy volunteers and those with T2DM.
Management Commentary
"Completion of patient dosing in the Phase 2a clinical trial of DA-1241, in patients with presumed MASH, marks an important milestone for this promising cardiometabolic asset, bringing us one step closer to the topline data readout from both Part 1 and Part 2 of the Phase 2a clinical trial expected in December of this year," stated Hyung Heon Kim, President and Chief Executive Officer of NeuroBo.
