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

• Sponsor: HepQuant, LLC (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT03294941
• Collaborator: (none)
• Enrollment: 17
• Locations: 8
• Arm: 1
• Actual Duration (Months): 21.1
• Patients Per Site: 2.1
• Patients Per Site Per Month: 0.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
NASH - Nonalcoholic Steatohepatitis	Combination Product: HepQuant SHUNT Liver Diagnostic Kit	Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Sequential Assignment
• Intervention 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.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)
• Primary Purpose: Diagnostic
• Official Title: The HepQuant SHUNT Test for Monitoring Liver Disease and Treatment Effects by Measuring Liver Function and Physiology
• Actual Study Start Date: Dec 8, 2017
• Actual Primary Completion Date: Sep 11, 2019
• Actual Study Completion Date: Sep 11, 2019

Arms and Interventions

Arm	Intervention/Treatment
Other: 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	Combination Product: HepQuant SHUNT Liver Diagnostic Kit; Serial testing over 48 weeks; Other Names: SHUNT test

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Schiff Center for Liver Diseases	Miami	Florida	United States	33136
2	University of PA	Philadelphia	Pennsylvania	United States	19104
3	Methodist Dallas Medical Center	Dallas	Texas	United States	75203
4	TX Digestive Disease Consultants	Dallas	Texas	United States	76092
5	The Texas Liver Institute	San Antonio	Texas	United States	78215
6	McGuire VA Med Cntr	Richmond	Virginia	United States	23224
7	Virginia Commonwealth University	Richmond	Virginia	United States	23298
8	University of Washingtion	Seattle	Washington	United States	98103

Sponsors and Collaborators

• HepQuant, LLC

Investigators

• Study Director: Greg Everson, MD, HepQuant, LLC

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - May 15, 2018

More Information

Publications

None provided.

• Responsible Party: HepQuant, LLC
• ClinicalTrials.gov Identifier: NCT03294941
• Other Study ID Numbers: HQ-US-SHUNT-1701
• First Posted: Sep 27, 2017
• Last Update Posted: Aug 9, 2021
• Last Verified: Aug 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease

Study Results

Participant Flow

Arm/Group Title	HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study	HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study
Arm/Group Description	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks
Period Title: Overall Study
STARTED	4	13
COMPLETED	4	11
NOT COMPLETED	0	2

Baseline Characteristics

Arm/Group Title	HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study	HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study	Total
Arm/Group Description	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks	Total of all reporting groups
Overall Participants	4	13	17
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	48.75	58.15	55.94
Sex: Female, Male (Count of Participants)
Female	4 100%	11 84.6%	15 88.2%
Male	0 0%	2 15.4%	2 11.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	3 75%	7 53.8%	10 58.8%
Not Hispanic or Latino	1 25%	6 46.2%	7 41.2%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	4 100%	13 100%	17 100%

Outcome Measures

1. Primary Outcome

Title	Baseline DSI
Description	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).
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study	HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study
Arm/Group Description	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks
Measure Participants	4	13
Mean (Standard Deviation) [score on a scale]	21.63 (3.31)	20.93 (3.55)

2. Primary Outcome

Title	Change in DSI From Baseline to 48 Weeks
Description	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).
Time Frame	Baseline and at 48 weeks

Outcome Measure Data

Analysis Population Description

15 subjects completed the week 48 SHUNT Test (4 in parallel study placebo group, and 11 in parallel study active study drug group), however, the SHUNT Test samples were unanalyzable for 1 subject on active study drug due to failure of the IV Clearance component of the SHUNT Test. Therefore, the present analysis only includes 14 subjects (4 on placebo, 10 on active study drug).

Arm/Group Title	HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study	HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study
Arm/Group Description	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks
Measure Participants	4	10
Mean (Standard Deviation) [score on a scale]	-1.08 (2.44)	-1.00 (2.28)

3. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was conducted to compare DSI scores between Fibrosis categories instead of by placebo vs active study drug groups because the subject numbers were too low. There was only one subject in the placebo group with F4 Fibrosis. Additionally, this outcome measure was established to compare DSI scores to other liver disease severity scores regardless of study drug use, so this analysis was conducted by grouping fibrosis scores.

Arm/Group Title	HepQuant SHUNT Liver Diagnostic Kit - Subjects With F3 Fibrosis	HepQuant SHUNT Liver Diagnostic Kit - Subjects With F4 Fibrosis
Arm/Group Description	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks
Measure Participants	9	8
Mean (Standard Deviation) [score on a scale]	19.39 (1.70)	23.02 (3.91)

Adverse Events

Time Frame	12 months, from the date of enrollment through the 48 week/final study visit.
Adverse Event Reporting Description	Adverse events are all grouped together because the only intervention in the HepQuant Study is the HepQuant SHUNT Test. Although 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, the HepQuant study itself had only one arm.
Arm/Group Title	HepQuant SHUNT Liver Diagnostic Kit
Arm/Group Description	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 HepQuant SHUNT Liver Diagnostic Kit: Serial testing over 48 weeks
All Cause Mortality
	HepQuant SHUNT Liver Diagnostic Kit
	Affected / at Risk (%)	# Events
Total	0/17 (0%)
Serious Adverse Events
	HepQuant SHUNT Liver Diagnostic Kit
	Affected / at Risk (%)	# Events
Total	0/17 (0%)
Other (Not Including Serious) Adverse Events
	HepQuant SHUNT Liver Diagnostic Kit
	Affected / at Risk (%)	# Events
Total	3/17 (17.6%)
Injury, poisoning and procedural complications
Mild IV-related events	3/17 (17.6%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.