Last updated on February 2018

Trial to Examine the Effect of Two Doses of GRI-0621 in Patients With Chronic Liver Disease


Brief description of study

Primary objectives:

To evaluate the change in serum alanine transaminase [ALT] levels from Day 0 to Day 28, following daily doses of 4.5 or 6mg of GRI-0621 compared to placebo, in patients with chronic liver disease and elevated serum levels of ALT. Serum ALT level will be used as a marker of liver inflammation.

To assess the safety and tolerability of GRI-0621 at these two doses.

Secondary objectives:

To assess the change in serum aspartate transaminase [AST] levels from baseline to Day 28, following daily doses of 4.5 or 6mg of GRI-0621 or matching placebo, in patients with chronic liver disease and elevated serum levels of AST. Serum AST level will be used as a second marker of liver inflammation.

To evaluate the response to 4.5mg GRI-0621 versus 6mg GRI-0621 in terms of the change in serum ALT levels from baseline measured at the different trial time points.

To assess changes in serum cytokeratin 18 [CK-18] levels from baseline to Day 28, following daily doses of 4.5 or 6mg of GRI-0621 or matching placebo, in patients with chronic liver disease. Serum CK-18 is used as a marker of hepatocyte cell death due to either necrosis or apoptosis.

To measure Natural Killer T lymphocyte [NKT] cell activity at baseline and at Day 28 following daily doses of 4.5 or 6mg of GRI-0621 or matching placebo.

To describe the steady-state pharmacokinetics [PK] of GRI-0621 in patients with chronic liver disease.

Exploratory objectives:

To assess the effect, if any, that the investigational product may have on serum triglyceride levels.

Detailed Study Description

This is a multi- centre, double-blind, randomized, placebo-controlled phase 2a trial in participants aged 18 to 65 years with chronic liver disease. It is designed to assess the safety, tolerability and efficacy of both 4.5mg and 6mg of GRI-0621 when administered once daily for 28 days.

A total of 60 participants will be randomised to received 4.5mg or 6mg of GRI-0621 or matching placebo in a 1:1:1 ratio. The investigational product will be administered orally once daily in the morning for a duration of 28 days. Participants will return to the clinic for follow-up safety and efficacy assessments on Days 7, 14, 21 and 28. Additionally, PK sampling will be performed on Days 7 and 28, and samples for immunological assays to assess the activity of NKT cells will be drawn on Days 0 (baseline) and 28. An end-of-trial follow-up visit will be performed 14 days after the last dose of the investigational product on Day 42.

The primary efficacy objective will be measured by the change from baseline to Day 28 in serum ALT levels. The baseline ALT level will be calculated as the mean of the Day -7 to -1 and Day 0 serum ALT results.

Safety and tolerability will be measured by the incidence and severity of adverse events and changes in physical examination findings, physical measurements, vital signs, ECG findings and standard laboratory safety parameters (including hematology, clinical chemistry, coagulation parameters and urinalysis).

Clinical Study Identifier: NCT02949375

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Mpho Klass Kgomo, MBBCH

Steve Biko Academic Hospital
Pretoria, South Africa
2.79miles
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