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

NCT ID: NCT03087968

Last Updated: 2021-08-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

EARLY_PHASE1

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-31

Study Completion Date

2017-09-13

Brief Summary

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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

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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

Conditions

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Severe Alcoholic Hepatitis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

DOUBLE

Participants Caregivers

Study Groups

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GS-4997 + Prednisolone

GS-4997 + Prednisolone for 28 days

HepQuant SHUNT Test

Group Type EXPERIMENTAL

GS-4997

Intervention Type DRUG

Experimental drug

Prednisolone

Intervention Type DRUG

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

HepQuant SHUNT Test

Intervention Type DEVICE

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.

Prednisolone + Placebo

Placebo + Prednisolone for 28 days

HepQuant SHUNT Test

Group Type PLACEBO_COMPARATOR

Prednisolone

Intervention Type DRUG

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

HepQuant SHUNT Test

Intervention Type DEVICE

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.

Placebo

Intervention Type DRUG

Placebo

Interventions

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GS-4997

Experimental drug

Intervention Type DRUG

Prednisolone

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

Intervention Type DRUG

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.

Intervention Type DEVICE

Placebo

Placebo

Intervention Type DRUG

Other Intervention Names

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SHUNT

Eligibility Criteria

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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

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;
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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HepQuant, LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Greg Everson, MD

Role: PRINCIPAL_INVESTIGATOR

HepQuant, LLC

Locations

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Southern California Research Center

Coronado, California, United States

Site Status

University of Miami

Miami, Florida, United States

Site Status

Emory University

Atlanta, Georgia, United States

Site Status

University of Minnesota

Minneapolis, Minnesota, United States

Site Status

University of Mississippi Medical Center

Jackson, Mississippi, United States

Site Status

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

The Liver Institute at Methodist Dallas Medical Center

Dallas, Texas, United States

Site Status

American Research Corporation at the Texas Liver Institute

San Antonio, Texas, United States

Site Status

Intermountain Medical Center

Murray, Utah, United States

Site Status

Liver Institute of Virginia

Newport News, Virginia, United States

Site Status

Liver Institute of Virginia

Richmond, Virginia, United States

Site Status

VCU Health System

Richmond, Virginia, United States

Site Status

University of Washington

Seattle, Washington, United States

Site Status

Countries

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United States

Other Identifiers

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HepQuant-002-2124

Identifier Type: -

Identifier Source: org_study_id

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