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Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension.

Abstract：

BACKGROUND & AIMS:Increased levels of galectin 3 have been associated with nonalcoholic steatohepatitis (NASH) and contribute to toxin-induced liver fibrosis in mice. GR-MD-02 (belapectin) is an inhibitor of galectin 3 that reduces liver fibrosis and portal hypertension in rats and was safe and well tolerated in phase 1 studies. We performed a phase 2b, randomized trial of the safety and efficacy of GR-MD-02 in patients with NASH, cirrhosis, and portal hypertension. METHODS:Patients with NASH, cirrhosis, and portal hypertension (hepatic venous pressure gradient [HVPG] ≥ 6 mm Hg) from 36 centers were randomly assigned, in a double-blind manner, to groups that received biweekly infusions of belapectin 2 mg/kg (n = 54), 8 mg/kg (n = 54), or placebo (n = 54) for 52 weeks. The primary endpoint was change in HVPG (Δ HVPG) at the end of the 52-week period compared with baseline. Secondary endpoints included changes in liver histology and development of liver-related outcomes. RESULTS:We found no significant difference in ΔHVPG between the 2 mg/kg belapectin group and placebo group (-0.28 mm HG vs 0.10 mm HG, P = 1.0) or between the 8 mg/kg belapectin and placebo group (-0.25 mm HG vs 0.10 mm HG, P = 1.0). Belapectin had no significant effect on fibrosis or nonalcoholic fatty liver disease activity score, and liver-related outcomes did not differ significantly among groups. In an analysis of a subgroup of patients without esophageal varices at baseline (n = 81), 2 mg/kg belapectin was associated with a reduction in HVPG at 52 weeks compared with baseline (P = .02) and reduced development of new varices (P = .03). Belapectin (2 mg/kg) was well tolerated and produced no safety signals. CONCLUSIONS:In a phase 2b study of 162 patients with NASH, cirrhosis, and portal hypertension, 1 year of biweekly infusion of belapectin was safe but not associated with significant reduction in HVPG or fibrosis compared with placebo. However, in a subgroup analysis of patients without esophageal varices, 2 mg/kg belapectin did reduce HVPG and development of varices. ClinicalTrials.gov number: NCT02462967.

journal_name

Gastroenterology

journal_title

Gastroenterology

authors

Chalasani N,Abdelmalek MF,Garcia-Tsao G,Vuppalanchi R,Alkhouri N,Rinella M,Noureddin M,Pyko M,Shiffman M,Sanyal A,Allgood A,Shlevin H,Horton R,Zomer E,Irish W,Goodman Z,Harrison SA,Traber PG,Belapectin (GR-MD-02) Stud

doi

10.1053/j.gastro.2019.11.296

subject

Has Abstract

pub_date

2020-04-01 00:00:00

pages

1334-1345.e5

issue

eissn

0016-5085

issn

1528-0012

pii

S0016-5085(19)41895-7

journal_volume

158

pub_type

杂志文章,多中心研究,随机对照试验

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Effects of Belapectin, an Inhibitor of Galectin-3, in Patients With Nonalcoholic Steatohepatitis With Cirrhosis and Portal Hypertension.