Severe Alcoholic Hepatitis
Conditions
Brief summary
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.
Detailed description
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
Interventions
DRUGGS-4997
Experimental drug
DRUGPrednisolone
Control drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms.
DEVICEHepQuant SHUNT Test
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.
DRUGPlacebo
Placebo
Sponsors
HepQuant, LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms | HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Outcome 1 | HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24 | To determine the relationship of baseline Disease Severity Index (DSI) to mortality risk; |
| Secondary Outcome 2 | HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24 | To determine the relationship of change in Disease Severity Index (DSI) to mortality risk |
| Secondary Outcome 3 | HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24 | To correlate baseline Disease Severity Index (DSI) with baseline Maddrey, MELD, and Lille scorestest with the pharmacokinetics of GS-4997 |
| Secondary Outcome 4 | HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24 | To determine the relationship between baseline Disease Severity Index (DSI), Maddrey, MELD, and Lille scores and mortality |
Countries
United States
Outcome results
None listed