LP18 : Obeticholic acid for NASH: benefits in a high risk subgroup and the effects of concomitant statin use

Abstract

of cirrhosis is highly desirable because it simplifies post-LT management. Material and Methods: In this adaptive open-label, prospective randomized phase III North American clinical trial (Study 988, NCT01804829) conducted in 2 parts, any antiviral therapy (AVT) pre-LT (resulting in RNA <100 IU/ml prior to transplant) is followed in the active treatment arms by Hepatitis C Immune Globulin (HCIG, Civacir) periand post-LT to prevent HCV infection after LT. In part I (dose finding), patients were randomized 1:1:1 to active (200 or 300mg/kg) or control arms. Active group patients received 16 infusions of Civacir in the periand immediate post-LT period for 10 weeks. Control patients received standard of care (no treatment) immediately after LT. The primary endpoint is sustained virologic response SVR12. Results: Three quarters (N=63 as of 27 Jan 2015) of 84 planned patients have been enrolled. Preliminary efficacy evaluations justified continued enrollment in the 300mg/kg arm but not in the 200mg/kg low dose arm (closed by amendment). Treatment and control arms are comparable at baseline. Mean age of patients is 61 and 84% are male. 93% of patients were treated with sofosbuvirbased regimens pre-LT, for a median duration of 63.5 days including 9.4% with treatment <4 weeks. To date, 1/21 (5%) reinfection was observed in the 300mg/kg arm. In the control and 200mg/kg arm 7/22 (32%) and 6/20 (30%) reinfections occurred, respectively. At day 6, 14, 21 and 28 post-LT the median anti-HCV antibody titer was 440, 312, 274 and 215 U/ml in the 300mg/kg and 39, 44, 53 and 63 U/ml in the control arm. Civacir has been well tolerated with no drug-related serious adverse events to date. The most frequent reported AEs were those well-known for human immunoglobulins, underlying disease, and surgical associated events.