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

Sponsor

HepQuant, LLC (Industry)

Overall Status

Withdrawn

CT.gov ID

NCT03087968

Collaborator

(none)

Enrollment

Locations

Arms

13.4

Anticipated Duration (Months)

Patients Per Site

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Severe Alcoholic Hepatitis	Drug: GS-4997 Drug: Prednisolone Device: HepQuant SHUNT Test Drug: Placebo	Early Phase 1

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

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Care Provider)

Primary Purpose:

Diagnostic

Official Title:

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

Anticipated Study Start Date :

Jul 31, 2016

Actual Primary Completion Date :

Sep 13, 2017

Actual Study Completion Date :

Sep 13, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: GS-4997 + Prednisolone GS-4997 + Prednisolone for 28 days HepQuant SHUNT Test	Drug: GS-4997 Experimental drug Drug: Prednisolone Control drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms. Device: HepQuant 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. Other Names: SHUNT
Placebo Comparator: Prednisolone + Placebo Placebo + Prednisolone for 28 days HepQuant SHUNT Test	Drug: Prednisolone Control drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms. Device: HepQuant 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. Other Names: SHUNT Drug: Placebo Placebo

Arm

Intervention/Treatment

Experimental: GS-4997 + Prednisolone

GS-4997 + Prednisolone for 28 days HepQuant SHUNT Test

Drug: GS-4997

Experimental drug

Drug: Prednisolone

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

Device: HepQuant 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.

Other Names:

SHUNT

Placebo Comparator: Prednisolone + Placebo

Placebo + Prednisolone for 28 days HepQuant SHUNT Test

Drug: Prednisolone

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

Device: HepQuant SHUNT Test

Other Names:

SHUNT

Drug: Placebo

Placebo

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Southern California Research Center	Coronado	California	United States	92118
2	University of Miami	Miami	Florida	United States	33136
3	Emory University	Atlanta	Georgia	United States	30322
4	University of Minnesota	Minneapolis	Minnesota	United States	55455
5	University of Mississippi Medical Center	Jackson	Mississippi	United States	39216
6	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
7	The Liver Institute at Methodist Dallas Medical Center	Dallas	Texas	United States	75203
8	American Research Corporation at the Texas Liver Institute	San Antonio	Texas	United States	78215
9	Intermountain Medical Center	Murray	Utah	United States	84107
10	Liver Institute of Virginia	Newport News	Virginia	United States	23602
11	Liver Institute of Virginia	Richmond	Virginia	United States	23226
12	VCU Health System	Richmond	Virginia	United States	23298
13	University of Washington	Seattle	Washington	United States	98104

Sponsors and Collaborators

HepQuant, LLC

Investigators

Principal Investigator: Greg Everson, MD, HepQuant, LLC

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

HepQuant, LLC

ClinicalTrials.gov Identifier:

NCT03087968

Other Study ID Numbers:

HepQuant-002-2124

First Posted:

Mar 23, 2017

Last Update Posted:

Aug 30, 2021

Last Verified:

Sep 1, 2017

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Yes

Additional relevant MeSH terms:

Liver Diseases

Hepatitis, Alcoholic

Prednisolone

Study Results

No Results Posted as of Aug 30, 2021