Study design
liver stiffness, PSC
PRIMARY SCLEROSING CHOLANGITIS, RECRUITMENT
This phase 3 study consists of 2 phases: a blinded phase and an open-label extension (OLE) phase (Fig. PRIMIS study design. PSC, primary sclerosing cholangitis; UDCA, ursodeoxycholic acidPatients who do not permanently discontinue study drug and complete the blinded phase Week 96 or follow-up visit are eligible to enter the OLE phase, and receive open-label cilofexor 100 mg daily for up to 96 weeks. The OLE phase includes a 4-week rollover period, 96 weeks of treatment, and a follow-up visit 4 weeks after completion of OLE Week 96 or ET. After rollover, in-clinic study visits occur at OLE baseline, Weeks 4, 24, 48, 72, and 96 or ET, and the follow-up visit. This 96-week OLE phase will provide additional data regarding the long-term safety and efficacy of cilofexor.The study was initiated in March 2019 with an initial focus on activation of North American study sites. In autumn 2019, changes to the protocol were made with an amendment based on patient and investigator requests to decrease study burden and reduce recruitment delays. These changes included increasing the upper age cutoff from 70 to 75 years, extension of the screening window from 8 to 10 weeks, addition of a 14-day visit window for the initial MRCP, and an optional liver stiffness measurement by VCTE. Due to the Covid-19 pandemic, and requests by sites and potential subjects to facilitate enrollment, an additional amendment was initiated in the spring of 2020 that included reductions in the numbers of on-site study visits, collections of samples for biomarkers, and PSC-related HRQOL questionnaires. A fourth amendment in June 2021 added an interim futility analysis based on the primary endpoint after the first 160 randomized and dosed patients completed the blinded phase of the study and the OLE phase, based on requests of patients and investigators.