A randomized placebo-controlled trial of elafibranor in patients with primary biliary cholangitis and incomplete response to UDCA.

Abstract

BACKGROUND AND AIM\nPatients with primary biliary cholangitis (PBC) who have an incomplete response to ursodeoxycholic acid remain at risk of disease progression. We investigated the safety and efficacy of elafibranor, a dual PPARα/δ agonist, in patients with PBC.\n\n\nMETHODS\nThis 12-week, double blind phase 2 trial enrolled 45 adults with PBC who had incomplete response to ursodeoxycholic acid (alkaline phosphatase levels ≥1.67-fold the upper limit of normal (ULN). Patients were randomly assigned to elafibranor-80 mg, elafibranor-120 mg or placebo. The primary end-point was the relative change of ALP at 12 weeks (NCT03124108).\n\n\nRESULTS\nReductions of ALP at 12 weeks were -48.3±14.8% for elafibranor-80 mg (p<0.001 vs placebo), -40.6±17.4% for elafibranor-120 mg (p<0.001) and +3.2±14.8% in the placebo group. The composite endpoint of ALP≤1.67-fold the ULN, decrease of ALP >15% and total bilirubin below the ULN was achieved in 67% patients in the elafibranor-80 mg group and 79% patients in the elafibranor-120 mg group, versus 6.7% patients in the placebo group. Levels of gamma glutamyl transferase decreased by 37.0±25.5% in the elafibranor-80mg group (p<0.001), 40.0±24.1% in the elafibranor-120mg group (p<0.01) compared with no change (+0.2±26.0%) in the placebo group. Levels of disease markers such as IgM, 5 -nucleotidase or hsCRP were likewise reduced from elafibranor. Pruritus was not induced or exacerbated from elafibranor and patients with pruritus at baseline reported less pruritic symptoms at the end of treatment. All possibly drug related non-serious adverse events were mild to moderate.\n\n\nCONCLUSION\nIn this randomized phase 2 trial, elafibranor was generally safe and well tolerated and significantly reduced levels of ALP, composite endpoints of bilirubin and ALP, as well as other markers of disease activity in patients with PBC and incomplete response to ursodeoxycholic acid. Data is available from the Study Sponsor Genfit SA.\n\n\nCLINICAL TRIAL REGISTRATION NUMBER\nClinical Trials.gov NCT03124108.