Safety, tolerability, and anti-fibrotic efficacy of the CBP/β-catenin inhibitor PRI-724 in patients with hepatitis C and B virus induced liver cirrhosis

Background: We assessed the safety, tolerability, and anti-fibrotic effects of PRI-724, CBP/β-catenin inhibitor, in patients with HCV and HBV cirrhosis. Methods: This multicenter, open-label, phase 1/2a trial was conducted at three hospitals. In phase 1, patients received intravenous infusion of PRI-724 at doses of 140, 280, or 380 mg/m² twice weekly for 12 weeks. In phase 2a, the recommended PRI-724 dose was administered. The primary endpoints were the frequency of AEs and efficacy in treating cirrhosis based on liver biopsy. Results: Between July 2018, and July 2021, 15 patients were enrolled in phase 1 and 12 patients in phase 2a. Three patients from phase 1 who received the recommended PRI-724 dose were evaluated in phase 2a. SAEs occurred in three patients (11%, 3/27), one of which was possibly related to PRI-724. PRI-724 did not significantly decrease the area of reticular fibers in the hepatic lobule at 12 weeks; however, we observed significant improvements in LSM, MELD score, and serum albumin level. Conclusion: The findings showed that 280 mg/m² PRI-724 over 12 weeks was preliminary well tolerated by patients with HCV and HBV cirrhosis.