NASH - Nonalcoholic Steatohepatitis
Conditions
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
Interventions
COMBINATION_PRODUCTHepQuant SHUNT Liver Diagnostic Kit
Serial testing over 48 weeks
Sponsors
HepQuant, LLC
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
DIAGNOSTIC
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study 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 | 4 |
| HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study 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 | 13 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 2 |
Baseline characteristics
| Characteristic | HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study | HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study | Total |
|---|---|---|---|
| Age, Continuous | 48.75 years | 58.15 years | 55.94 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants | 6 Participants | 7 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 4 participants | 13 participants | 17 participants |
| Sex: Female, Male Female | 4 Participants | 11 Participants | 15 Participants |
| Sex: Female, Male Male | 0 Participants | 2 Participants | 2 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 17 |
| other Total, other adverse events | 3 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
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).
Time frame: Baseline
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study | Baseline DSI | 21.63 score on a scale | Standard Deviation 3.31 |
| HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study | Baseline DSI | 20.93 score on a scale | Standard Deviation 3.55 |
Primary
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).
Time frame: Baseline and at 48 weeks
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study | Change in DSI From Baseline to 48 Weeks | -1.08 score on a scale | Standard Deviation 2.44 |
| HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study | Change in DSI From Baseline to 48 Weeks | -1.00 score on a scale | Standard Deviation 2.28 |
Secondary
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.
Time frame: Baseline
Population: 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 | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| HepQuant SHUNT Liver Diagnostic Kit - Placebo in Parallel Study | Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis | 19.39 score on a scale | Standard Deviation 1.7 |
| HepQuant SHUNT Liver Diagnostic Kit - Active Study Drug in Parallel Study | Severity of Liver Disease Index (DSI) Scores Stratified by Baseline NASH CRN Stage of Fibrosis | 23.02 score on a scale | Standard Deviation 3.91 |