학술논문
Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis
Document Type
article
Author
Richard J. Thompson; Reha Artan; Ulrich Baumann; Pier Luigi Calvo; Piotr Czubkowski; Buket Dalgic; Lorenzo D’Antiga; Angelo Di Giorgio; Özlem Durmaz; Emmanuel Gonzalès; Tassos Grammatikopoulos; Girish Gupte; Winita Hardikar; Roderick H.J. Houwen; Binita M. Kamath; Saul J. Karpen; Florence Lacaille; Alain Lachaux; Elke Lainka; Kathleen M. Loomes; Cara L. Mack; Jan P. Mattsson; Patrick McKiernan; Quanhong Ni; Hasan Özen; Sanjay R. Rajwal; Bertrand Roquelaure; Eyal Shteyer; Etienne Sokal; Ronald J. Sokol; Nisreen Soufi; Ekkehard Sturm; Mary Elizabeth Tessier; Wendy L. van der Woerd; Henkjan J. Verkade; Jennifer M. Vittorio; Terese Wallefors; Natalie Warholic; Qifeng Yu; Patrick Horn; Lise Kjems
Source
JHEP Reports, Vol 5, Iss 8, Pp 100782- (2023)
Subject
Language
English
ISSN
2589-5559
Abstract
Background & Aims: PEDFIC 2, an ongoing, open-label, 72-week study, evaluates odevixibat, an ileal bile acid transporter inhibitor, in patients with progressive familial intrahepatic cholestasis. Methods: PEDFIC 2 enrolled and dosed 69 patients across two cohorts; all received odevixibat 120 μg/kg per day. Cohort 1 comprised children from PEDFIC 1, and cohort 2 comprised new patients (any age). We report data through 15 July 2020, with Week 24 of PEDFIC 2 the main time point analysed. This represents up to 48 weeks of cumulative exposure for patients treated with odevixibat from the 24-week PEDFIC 1 study (cohort 1A) and up to 24 weeks of treatment for those who initiated odevixibat in PEDFIC 2 (patients who received placebo in PEDFIC 1 [cohort 1B] or cohort 2 patients). Primary endpoints for this prespecified interim analysis were change from baseline to Weeks 22–24 in serum bile acids (sBAs) and proportion of positive pruritus assessments (≥1-point drop from PEDFIC 2 baseline in pruritus on a 0–4 scale or score ≤1) over the 24-week period. Safety monitoring included evaluating treatment-emergent adverse events (TEAEs). Results: In cohort 1A, mean change from PEDFIC 1 baseline to Weeks 22–24 of PEDFIC 2 in sBAs was -201 μmol/L (p