Back to resultsEvaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
Primary Purpose
Severe Alcoholic Hepatitis
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
GS-4997
Prednisolone
HepQuant SHUNT Test
Placebo
Sponsored by
About this trial
This is an interventional diagnostic trial for Severe Alcoholic Hepatitis
Eligibility Criteria
Inclusion Criteria:
- 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)
- Clinical diagnosis of severe AH
- Maddrey's DF ≥ 32 at screening
Exclusion Criteria:
Key Exclusion Criteria:
- Pregnant or lactating females;
- 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;
- Serum AST >400 U/L or ALT >300 U/L;
- MELD >30 at screening;
- Maddrey's DF >60 at screening;
- Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
- Concomitant or previous history of hepatocellular carcinoma;
- History of liver transplantation;
- HIV Ab positive;
- Clinical suspicion of pneumonia;
- Uncontrolled sepsis;
- 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;
- 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;
- Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
- Portal vein thrombosis;
- Acute pancreatitis;
- Cessation of alcohol consumption for more than 2 months before Baseline/ Day 1 NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Sites / Locations
- Southern California Research Center
- University of Miami
- Emory University
- University of Minnesota
- University of Mississippi Medical Center
- University of Pennsylvania
- The Liver Institute at Methodist Dallas Medical Center
- American Research Corporation at the Texas Liver Institute
- Intermountain Medical Center
- Liver Institute of Virginia
- Liver Institute of Virginia
- VCU Health System
- University of Washington
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
GS-4997 + Prednisolone
Prednisolone + Placebo
Arm Description
GS-4997 + Prednisolone for 28 days HepQuant SHUNT Test
Placebo + Prednisolone for 28 days HepQuant SHUNT Test
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
Secondary Outcome 1
To determine the relationship of baseline Disease Severity Index (DSI) to mortality risk;
Secondary Outcome 2
To determine the relationship of change in Disease Severity Index (DSI) to mortality risk
Secondary Outcome 3
To correlate baseline Disease Severity Index (DSI) with baseline Maddrey, MELD, and Lille scorestest with the pharmacokinetics of GS-4997
Secondary Outcome 4
To determine the relationship between baseline Disease Severity Index (DSI), Maddrey, MELD, and Lille scores and mortality
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03087968
Brief Title
Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
Official Title
Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
Study Type
Interventional
2. Study Status
Record Verification Date
September 2017
Overall Recruitment Status
Withdrawn
Why Stopped
No longer a sub-study - Changing to an independent parallel study
Study Start Date
July 31, 2016 (Anticipated)
Primary Completion Date
September 13, 2017 (Actual)
Study Completion Date
September 13, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
HepQuant, LLC
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Severe Alcoholic Hepatitis
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Early Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
GS-4997 + Prednisolone
Arm Type
Experimental
Arm Description
GS-4997 + Prednisolone for 28 days
HepQuant SHUNT Test
Arm Title
Prednisolone + Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo + Prednisolone for 28 days
HepQuant SHUNT Test
Intervention Type
Drug
Intervention Name(s)
GS-4997
Intervention Description
Experimental drug
Intervention Type
Drug
Intervention Name(s)
Prednisolone
Intervention Description
Control drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms.
Intervention Type
Device
Intervention Name(s)
HepQuant SHUNT Test
Other Intervention Name(s)
SHUNT
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms
Description
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.
Time Frame
HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome Measure Information:
Title
Secondary Outcome 1
Description
To determine the relationship of baseline Disease Severity Index (DSI) to mortality risk;
Time Frame
HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Title
Secondary Outcome 2
Description
To determine the relationship of change in Disease Severity Index (DSI) to mortality risk
Time Frame
HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Title
Secondary Outcome 3
Description
To correlate baseline Disease Severity Index (DSI) with baseline Maddrey, MELD, and Lille scorestest with the pharmacokinetics of GS-4997
Time Frame
HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Title
Secondary Outcome 4
Description
To determine the relationship between baseline Disease Severity Index (DSI), Maddrey, MELD, and Lille scores and mortality
Time Frame
HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
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)
Clinical diagnosis of severe AH
Maddrey's DF ≥ 32 at screening
Exclusion Criteria:
Key Exclusion Criteria:
Pregnant or lactating females;
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;
Serum AST >400 U/L or ALT >300 U/L;
MELD >30 at screening;
Maddrey's DF >60 at screening;
Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
Concomitant or previous history of hepatocellular carcinoma;
History of liver transplantation;
HIV Ab positive;
Clinical suspicion of pneumonia;
Uncontrolled sepsis;
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;
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;
Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
Portal vein thrombosis;
Acute pancreatitis;
Cessation of alcohol consumption for more than 2 months before Baseline/ Day 1 NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Greg Everson, MD
Organizational Affiliation
HepQuant, LLC
Official's Role
Principal Investigator
Facility Information:
Facility Name
Southern California Research Center
City
Coronado
State/Province
California
ZIP/Postal Code
92118
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
Emory University
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Mississippi Medical Center
City
Jackson
State/Province
Mississippi
ZIP/Postal Code
39216
Country
United States
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
The Liver Institute at Methodist Dallas Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75203
Country
United States
Facility Name
American Research Corporation at the Texas Liver Institute
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78215
Country
United States
Facility Name
Intermountain Medical Center
City
Murray
State/Province
Utah
ZIP/Postal Code
84107
Country
United States
Facility Name
Liver Institute of Virginia
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Liver Institute of Virginia
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23226
Country
United States
Facility Name
VCU Health System
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Facility Name
University of Washington
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
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