Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124

Early Phase 1WithdrawnNCT03087968

HepQuant, LLC

Overview

This clinical investigation is a substudy within GS-US-416-2124, IND 129570, which is A Phase 2, Double-Blind, Randomized Study Evaluating the Safety, Tolerability, and Efficacy of GS-4997 in Combination with Prednisolone versus Prednisolone Alone in Subjects with Severe Alcoholic Hepatitis. The use of the HepQuant SHUNT test is to assess liver disease severity before, during, and after treatment with GS-4997 or placebo, to assess liver disease severity.

The main study is a Phase 2, double blind, proof-of-concept, randomized study evaluating the safety, tolerability, and biological activity of GS-4997 in combination with prednisolone, compared to prednisolone alone, in subjects with severe, histologically-confirmed AH. This substudy uses the HepQuant SHUNT Liver Diagnostic test to assess severity of disease at baseline and to track disease progression or improvement over the 24 weeks of the study. The HepQuant SHUNT test will be performed at baseline (Day 1) and at Weeks 1, 2, 4, 12, and 24 regardless of treatment Arm. GS-4997 Dose and Mode of Administration. Subjects will be randomized 1:1 to either: * Treatment Group A: GS-4997 18 mg (1 x 18 mg tablet) AND prednisolone 40 mg (4 x 10 mg tablets), both administered orally once daily * Treatment Group B: GS-4997 placebo (1 tablet) AND prednisolone 40 mg (4 x 10 mg tablets), both administered orally once daily

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

DIAGNOSTIC

Masking

DOUBLE

Conditions

Severe Alcoholic Hepatitis

Interventions

GS-4997DRUG

Experimental drug

PrednisoloneDRUG

Control drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms.

HepQuant SHUNT TestDEVICE

The HepQuant SHUNT Liver Diagnostic Kit is intended for use in the quantitative detection of 13C-cholate and d4-cholate in blood serum, collected after the intravenous administration of 13C-cholate and the oral ingestion of d4-cholate. The device is indicated to assess the severity of liver disease. For use by health care professionals. Administer the test under a physician's supervision. The HepQuant Analytical Testing Laboratory must analyze the serum samples.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Willing and able to give informed consent prior to any study specific procedures being performed. In individuals with hepatic encephalopathy (HE) which may impair decision-making, consent will be obtained per hospital procedures (eg, by Legally Authorized Representative) 2. Clinical diagnosis of severe AH 3. Maddrey's DF ≥ 32 at screening Exclusion Criteria: Key Exclusion Criteria: 1. Pregnant or lactating females; 2. Other causes of liver disease including chronic hepatitis B (hepatitis B surface antigen \[HBsAg\] positive), chronic hepatitis C (HCV RNA positive), acetaminophen hepatotoxicity, biliary obstruction, and autoimmune liver disease; 3. Serum AST \>400 U/L or ALT \>300 U/L; 4. MELD \>30 at screening; 5. Maddrey's DF \>60 at screening; 6. Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria; 7. Concomitant or previous history of hepatocellular carcinoma; 8. History of liver transplantation; 9. HIV Ab positive; 10. Clinical suspicion of pneumonia; 11. Uncontrolled sepsis; 12. Uncontrolled gastrointestinal (GI) bleeding or controlled GI bleeding within 7 days of screening that was associated with shock or required transfusion of more than 3 units of blood; 13. Type 1 hepatorenal syndrome (HRS) or renal failure defined as a serum creatinine \>221 μmol/L (\>2.5 mg/dL) or the requirement for renal replacement therapy; 14. Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation); 15. Portal vein thrombosis; 16. Acute pancreatitis; 17. Cessation of alcohol consumption for more than 2 months before Baseline/ Day 1 NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.

Locations (13)

Southern California Research Center

Coronado, California, United States

University of Miami

Miami, Florida, United States

Emory University

Atlanta, Georgia, United States

Outcomes

Primary Outcomes

To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms

Using the SHUNT DSI to evaluate the liver, this outcome will compare the two arms to determine if SHUNT DSI is able to measure a change between the experimental and control groups.