The HepQuant SHUNT Test for Monitoring Liver Disease and Treatment Effects by Measuring Liver Function and Physiology

Phase 2

Terminated

Conditions: NASH - Nonalcoholic Steatohepatitis

Interventions: Combination Product: HepQuant SHUNT Liver Diagnostic Kit

Registration Number: NCT03294941

Lead Sponsor: HepQuant, LLC

Brief Summary: The HepQuant SHUNT test, which is provided as a HepQuant SHUNT Liver Diagnostic Kit, is a minimally-invasive test of liver function and physiology which has been designated by the FDA as an investigational drug/device combination product.

Enrollment into one of the 3 Gilead Selonsertib clinical trials (GS-US-416-2124, GS-US-384-1943/1944) is required for enrollment into the HepQuant study

Detailed Description: The HepQuant study is to run parallel to the Gilead clinical trials,GS-US-416-2124 trial of Alcoholic Hepatitis, GS-US-384-1943 trial of non-alcoholic steatohepatitis (NASH) fibrosis Stage 3 (STELLAR-3), and, GS-US-384-1944 trial of NASH and compensated cirrhosis (STELLAR-4). The time points for the HepQuant SHUNT tests coincide with pre-specified time points within the Gilead clinical trials. Subjects enrolled in GILEAD's STELLAR and Alcoholic hepatitis trials may participate concurrently in this HepQuant sponsored investigational device study at participating US sites only (IDEs as listed above) once approved by the applicable IRB/IEC.

The main eligibility criteria for enrollment into the HepQuant study is enrollment into one of the three Gilead clinical trials listed above.

The HepQuant SHUNT Test is minimally-invasive and measures hepatocyte function and inflow to the liver from the simultaneous clearances (hepatic filtration rates, HFRs) of cholate from systemic and portal circulations. The Test quantifies portal-systemic shunting (SHUNT) and generates a liver disease severity index (DSI). DSI is a score from 0 (no disease) to 50 (terminal illness) that is a composite of both HFRs and correlates with stage of fibrosis, presence of varices, especially large varices, and risk for future clinical outcomes. DSI is the primary output variable from the HepQuant SHUNT test. The HepQuant SHUNT test potentially satisfies the unmet medical need for a minimally-invasive test of global liver function and physiology

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 17

Inclusion Criteria

The key inclusion criteria for this HepQuant Parallel Study are the inclusion criteria into one of the Gilead selonsertib trials (GS-US-416-2124, GS-US-384-1943 or 1944). Once that has been met, subjects must:

Be able to ingest liquid by mouth
Have venous access to support a peripheral IV and 6 blood draws

Exclusion Criteria

The key exclusion criteria for this HepQuant Parallel Study are the exclusion criteria for one of the Gilead selonsertib trials (GS-US-416-2124, GS-US-384-1943 or 1944). If this has been met, the subject is not eligible to participate in HepQuant. If no exclusion criteria has been met for the Gilead selonsertib trial, ADDITIONAL exclusions for HepQuant are:

Subject should not have had first dose of selonsertib
Subject cannot take anything by mouth
Subject cannot be hypersensitive to eggs, albumin preparations, any ingredient in the formulation, or component of the container
Subject cannot have intercurrent medical or surgical illness (eg: acute MI, acute cerebral hemorrhage, sepsis)
subject cannot have had extensive resection of large segments of small intestine (short gut)
Subject cannot have severe gastroparesis

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
HepQuant SHUNT Liver Diagnostic Kit	HepQuant SHUNT Liver Diagnostic Kit	All subjects receive HepQuant SHUNT test and DSI measurement. HepQuant SHUNT is a combination product where 13C Cholate 20mg is administered intravenously once for each test and d4 Cholate 40mg is administered once orally for each test

Primary Outcome Measures

Name	Time	Method
Baseline DSI	Baseline	The baseline DSI, or disease severity index, is a measure of severity of liver disease at baseline. The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).
Change in DSI From Baseline to 48 Weeks	Baseline and at 48 weeks	Improvement or worsening of liver disease severity from baseline to the week 48 visit as measured by the change in the disease severity index (DSI) (DSI at 48 weeks minus DSI at baseline). The scores for DSI range on a scale from 0 (healthy liver) to 50 (severe liver disease).

Secondary Outcome Measures

Name	Time	Method
Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis	Baseline	Compared baseline disease severity index (DSI) scores, which are used to measure severity of liver disease on a scale from 0 (healthy liver) to 50 (severe liver disease), between subjects with F3 or F4 Fibrosis at baseline. Fibrosis stages were obtained clinically using the NASH CRN Scoring System to grade liver biopsy results. This scoring system yields scores ranging from F0 (no fibrosis/healthiest) to F4 (cirrhosis/severe disease). Subjects in this study either had F3 Fibrosis (bridging fibrosis) or F4 Fibrosis (cirrhosis), so F3 subjects have less severe disease than F4 subjects.

Trial Locations

Locations (8): Virginia Commonwealth University
🇺🇸
Richmond, Virginia, United States
Methodist Dallas Medical Center
🇺🇸
Dallas, Texas, United States
TX Digestive Disease Consultants
🇺🇸
Dallas, Texas, United States
University of PA
🇺🇸
Philadelphia, Pennsylvania, United States
University of Washingtion
🇺🇸
Seattle, Washington, United States
Schiff Center for Liver Diseases
🇺🇸
Miami, Florida, United States
The Texas Liver Institute
🇺🇸
San Antonio, Texas, United States
McGuire VA Med Cntr
🇺🇸
Richmond, Virginia, United States