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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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NASH - Nonalcoholic Steatohepatitis

Intervention / Treatment
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* Combination Product: HepQuant SHUNT Liver Diagnostic Kit


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Diagnostic
Intervention Model: Sequential Assignment
Interventional Model Description: All subjects receive HepQuant SHUNT test and DSI measurement, but must first be enrolled into one of the three Gilead clinical trials listed above before they can be enrolled in the HepQuant study. Since the assigned intervention, the HepQuant SHUNT test, is the same for all participants in all three Gilead clinical trials, there is only one arm and intervention for the HepQuant study itself. Some analyses are conducted by grouping subjects into those who took the placebo in the parallel drug study versus those who were on active study drug in the parallel study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: HepQuant SHUNT Liver Diagnostic Kit<br>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 | Combination Product: HepQuant SHUNT Liver Diagnostic Kit<br>* Serial testing over 48 weeks<br>* Other names: SHUNT test;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline DSI | 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). | Baseline | 
| Change in DSI From Baseline to 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). | Baseline and at 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis | 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. | Baseline |