Severe Alcoholic HepatitisEarly Phase 1NCT03087968
Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
A Early Phase 1 study testing GS-4997, Prednisolone and HepQuant SHUNT Test in people with Severe Alcoholic Hepatitis, run by HepQuant, LLC at 13 sites in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Severe Alcoholic Hepatitis
- What is being tested?
- GS-4997, Prednisolone and HepQuant SHUNT Test
- Type of treatment
- Pill or oral medicine, Injection or infusion, Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 13 sitesUnited States
- Study dates
- 31 Jul 2016to 13 Sep 2017
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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)
- Clinical diagnosis of severe AH
- Maddrey's DF ≥ 32 at screening
Who cannot join
- Pregnant or lactating females;
- 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;
- Serum AST >400 U/L or ALT >300 U/L;
- MELD >30 at screening;
- Maddrey's DF >60 at screening;
- Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
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- Concomitant or previous history of hepatocellular carcinoma;
- History of liver transplantation;
- HIV Ab positive;
- Clinical suspicion of pneumonia;
- Uncontrolled sepsis;
- 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;
- 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;
- Individuals dependent on inotropic (eg, epinephrine or norepinephrine) or ventilatory support (ie, endotracheal intubation or positive-pressure ventilation);
- Portal vein thrombosis;
- Acute pancreatitis;
- Cessation of alcohol consumption for more than 2 months before Baseline/ Day 1 NOTE: Other protocol defined Inclusion/ Exclusion criteria may apply.
Trial locations and contacts
13 sites in 1 country.
13 sites in 1 country
United States13 sites
Emory University
Atlanta, Georgia, 30322
Southern California Research Center
Coronado, California, 92118
The Liver Institute at Methodist Dallas Medical Center
Dallas, Texas, 75203
University of Mississippi Medical Center
Jackson, Mississippi, 39216
University of Miami
Miami, Florida, 33136
University of Minnesota
Minneapolis, Minnesota, 55455
Intermountain Medical Center
Murray, Utah, 84107
Liver Institute of Virginia
Newport News, Virginia, 23602
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
Liver Institute of Virginia
Richmond, Virginia, 23226
VCU Health System
Richmond, Virginia, 23298
American Research Corporation at the Texas Liver Institute
San Antonio, Texas, 78215
University of Washington
Seattle, Washington, 98104
About this study
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.
Read the detailed description
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
- Severe Alcoholic Hepatitis
- Being tested
- GS-4997, Prednisolone, HepQuant SHUNT Test, Placebo
- Medical subject headings
- Hepatitis, Alcoholic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GS-4997Drug
Experimental drug
PrednisoloneDrug
Control drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms.
HepQuant SHUNT TestDevice
Also called SHUNT
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| GS-4997 + Prednisolone | Experimental | GS-4997 + Prednisolone for 28 days
HepQuant SHUNT Test Receives: Drug: GS-4997; Drug: Prednisolone; Device: HepQuant SHUNT Test |
| Prednisolone + Placebo | Placebo comparator | Placebo + Prednisolone for 28 days
HepQuant SHUNT Test Receives: Drug: Prednisolone; Device: HepQuant SHUNT Test; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms
Using the SHUNT DSI to evaluate the liver, this outcome will compare the two arms to determine if SHUNT DSI is able to measure a change between the experimental and control groups.
Measured: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary outcomes (4)
Secondary Outcome 1
To determine the relationship of baseline Disease Severity Index (DSI) to mortality risk;
Measured: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome 2
To determine the relationship of change in Disease Severity Index (DSI) to mortality risk
Measured: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome 3
To correlate baseline Disease Severity Index (DSI) with baseline Maddrey, MELD, and Lille scorestest with the pharmacokinetics of GS-4997
Measured: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome 4
To determine the relationship between baseline Disease Severity Index (DSI), Maddrey, MELD, and Lille scores and mortality
Measured: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Mar 2017
- Study start31 Jul 2016 (estimated)
- Primary completion13 Sep 2017
- Study completion13 Sep 2017
Why it stopped: No longer a sub-study - Changing to an independent parallel study
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Alcoholic HepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- HepQuant, LLC
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Greg Everson, MD, Principal investigator, HepQuant, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03087968
- Sponsor's protocol ID
- HepQuant-002-2124
- Status last verified
- Sep 2017
- First submitted
- 9 Mar 2017
- Last updated
- 30 Aug 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluation of HepQuant SHUNT to Assess Liver Disease; Substudy Within GS-US-416-2124
- ClinicalTrials.gov ID
- NCT03087968
- Acronym / sponsor ID
- HepQuant-002-2124
- Conditions
- Severe Alcoholic Hepatitis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No longer a sub-study - Changing to an independent parallel study
- Enrolment
- 0 participants (actual)
- Lead sponsor
- HepQuant, LLCIndustry (pharma, biotech, devices)
- Study start
- 31 Jul 2016 (estimated)
- Primary completion
- 13 Sep 2017 (actual)
- Study completion
- 13 Sep 2017 (actual)
- First posted
- 23 Mar 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| GS-4997 + Prednisolone | Experimental | Drug: GS-4997, Drug: Prednisolone, Device: HepQuant SHUNT TestGS-4997 + Prednisolone for 28 days HepQuant SHUNT Test |
| Prednisolone + Placebo | Placebo comparator | Drug: Prednisolone, Device: HepQuant SHUNT Test, Drug: PlaceboPlacebo + Prednisolone for 28 days HepQuant SHUNT Test |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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)
- Clinical diagnosis of severe AH
- Maddrey's DF ≥ 32 at screening
Key exclusion criteria (17 listed)
- Pregnant or lactating females;
- 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;
- Serum AST >400 U/L or ALT >300 U/L;
- MELD >30 at screening;
- Maddrey's DF >60 at screening;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GS-4997Experimental drug | Drug | GS-4997 + Prednisolone |
| PrednisoloneControl drug that is also administered with the Experimental drug, GS-4997. This drug is used in both arms. | Drug | GS-4997 + Prednisolone, Prednisolone + Placebo |
| HepQuant SHUNT TestAlso: SHUNTThe 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. | Device | GS-4997 + Prednisolone, Prednisolone + Placebo |
| PlaceboPlacebo | Drug | Prednisolone + Placebo |
Primary outcome
To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms
Time frame: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Using the SHUNT DSI to evaluate the liver, this outcome will compare the two arms to determine if SHUNT DSI is able to measure a change between the experimental and control groups.
4 secondary outcomes
Secondary Outcome 1
Time frame: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome 2
Time frame: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome 3
Time frame: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Secondary Outcome 4
Time frame: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Greg Everson, MD principal investigator
HepQuant, LLC
13 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing GS-4997, Prednisolone and HepQuant SHUNT Test in people with Severe Alcoholic Hepatitis, run by HepQuant, LLC at 13 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 30 Aug 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To compare the change in (DSI ) Disease Severity Index between GS-4997 treatment and placebo arms (time frame: HepQuant Shunt testing will be done at baseline (Day1), Week 1, Week 4, Week 12, Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2021.