Safety and tolerability of OP-724 in patients with haemophilia and liver cirrhosis due to HIV/HCV coinfection: an investigator-initiated, open-label, non-randomised, single-centre, phase I study

Objective Patients with haemophilia and HIV who acquire hepatitis C virus (HCV) after receiving contaminated blood products can experience accelerated progression of liver fibrosis and a poor prognosis, making liver disease a prominent cause of mortality among these patients. In the current study, we aimed to evaluate the safety and tolerability of the potential antifibrotic agent OP-724—a CREB-binding protein/β-catenin inhibitor—in this patient subset. Design In this single-centre, open-label, non-randomised, phase I trial, we sequentially enrolled patients with cirrhosis following HIV/HCV coinfection classified as Child-Pugh (CP) class A or B. Five patients received an intravenous infusion of OP-724 at doses of 140 or 280 mg/m2 for 4 hours two times weekly over 12 weeks. The primary endpoint was the incidence of serious adverse events (SAEs). Secondary endpoints included the incidence of AEs and improved liver stiffness measure (LSM), as determined by vibration-controlled transient elastography. This study was registered at ClinicalTrials.gov ([NCT04688034][1]). Results Between 9 February 2021 and 5 July 2022, five patients (median age: 51 years) were enrolled. All five patients completed 12 cycles of treatment. SAEs were not observed. The most common AEs were fever (60%) and gastrointestinal symptoms (diarrhoea: 20%, enterocolitis: 20%). Improvements in LSM and serum albumin levels were also observed. Conclusion In this preliminary assessment, intravenous administration of 140 or 280 mg/m2/4 hours OP-724 over 12 weeks was well tolerated by patients with haemophilia combined with cirrhosis due to HIV/HCV coinfection. Hence, the antifibrotic effects of OP-724 warrant further assessment in patients with cirrhosis. Trial registration number [NCT04688034][1]. Data are available upon reasonable request. The anonymous data displayed in the manuscript will be made available on request from the corresponding author following the publication of this article. Data displayed in the manuscript or acquired during the clinical trial will be made available in a form that does not deviate from what is accepted by local regulatory authorities with respect to the handling of patient data and in adherence to the policies of the Tokyo Metropolitan Komagome Hospital. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT04688034&atom=%2Fbmjgast%2F11%2F1%2Fe001341.atom