Clinical trial NCT02854631: Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)
Official title: 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 (AH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Alcoholic Hepatitis (AH)
Keywords: Cirrhosis
Prednisone
Jaundice
Lead sponsor: Gilead Sciences
Sponsor class: INDUSTRY
First posted: 2016-08-03
Enrollment: 104
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to evaluate the safety and tolerability of selonsertib (GS-4997) in combination with prednisolone versus prednisolone alone in participants with severe alcoholic hepatitis (AH).


Eligibility criteria: Key Inclusion Criteria:

* 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 Discriminant Function (DF) ≥ 32 at screening

Key Exclusion Criteria:

* 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 aspartate aminotransferase (AST) \>400 U/L or alanine aminotransferase (ALT) \>300 U/L;
* Model for End Stage Liver Disease (MELD) \>30 at screening;
* Maddrey's DF \>60 at screening;
* Grade 4 Hepatic Encephalopathy (HE) by West Haven criteria;
* 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.

Primary outcomes:
measure: Percentage of Participants With Treatment-Emergent (TE) Adverse Events (AE), Serious AEs (SAE), AEs Leading to Premature Study Drug Discontinuation, and Grade 3 or 4 Laboratory Abnormalities
timeFrame: Up to Day 28 plus 30 days
Secondary outcomes:
measure: Percentage of Participants Who Died by Day 28
timeFrame: Day 28
measure: Percentage of Participants Who Died by Week 8
timeFrame: Week 8
measure: Percentage of Participants Who Died by Week 12
timeFrame: Week 12
measure: Percentage of Participants Who Died by Week 24
timeFrame: Week 24
measure: Percentage of Participants With Survival at Day 28 Using Kaplan-Meier
timeFrame: Day 28
measure: Percentage of Participants With Survival at Week 8 Using Kaplan-Meier
timeFrame: Week 8
measure: Percentage of Participants With Survival at Week 12 Using Kaplan-Meier
timeFrame: Week 12
measure: Percentage of Participants With Survival at Week 24 Using Kaplan-Meier
timeFrame: Week 24
measure: Percentage of Participants Who Received a Liver Transplant
timeFrame: Day 28, Week 8, Week 12, and Week 24
measure: Percentage of Participants With Hepatorenal Syndrome (HRS)
timeFrame: Up to 24 weeks
measure: Percentage of Participants With Infection
timeFrame: Up to 24 weeks
measure: Length of Hospital Stay
timeFrame: Up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: Alanine Aminotransferase (ALT)
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: Aspartate Aminotransferase (AST)
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: Gamma Glutamyl Transferase (GGT)
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: Alkaline Phosphatase
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: Bilirubin
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: Albumin
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Liver Biochemistry Tests: International Normalized Ratio (INR)
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Percentage of Participants With Lille Response (Score < 0.45) at Day 7
timeFrame: Day 7
measure: Percentage of Participants With a Lille Null Response (Score ≥ 0.56) at Day 7
timeFrame: Day 7
measure: Lille Score at Day 7 as a Continuous Variable
timeFrame: Day 7
measure: Percentage of Participants With Estimated Mortality at Month 2 and Month 6: Combined Scoring Including Lille Score at Day 7 and Baseline Model for End-Stage Liver Disease (MELD) Score
timeFrame: Baseline and Day 7 Time Points used to calculate Overall Mortality Risk at Months 2 and 6
measure: Change From Baseline in Prognostic Index: Model for End-Stage Liver Disease (MELD) Score
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Prognostic Index: Child-Pugh-Turcotte (CPT) Score
timeFrame: Baseline (Day 1) and up to 24 weeks
measure: Change From Baseline in Prognostic Index: Maddrey Discriminant Function (DF) Score
timeFrame: Baseline (Day 1) and up to 24 weeks
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Coronado
country: United States
facility: Southern California Research Centers
state: California
city: Los Angeles
country: United States
facility: Cedars Sinai Medical Center
state: California
city: Weston
country: United States
facility: Cleveland Clinic Florida
state: Florida
city: New Orleans
country: United States
facility: Oschner Medical Center
state: Louisiana
city: Boston
country: United States
facility: Beth Israel Deaconess Medical Center
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Dallas
country: United States
facility: Methodist Healthcare Dallas - The Liver Institute
state: Texas
city: Newport News
country: United States
facility: Liver Institute of Virginia
state: Virginia
city: Seattle
country: United States
facility: University of Washington
state: Washington
city: Graz
country: Austria
facility: Medizinische Universitat Graz
city: Innsbruck
country: Austria
facility: Universitätsklinik für Innere Medizin I
city: Vienna
country: Austria
facility: Medical University Vienna
city: Brussels
country: Belgium
facility: Cliniques Universitaires UCL Saint-Luc
city: Brussels
country: Belgium
facility: CUB Hopital Erasme
city: Ghent
country: Belgium
facility: Ghent University Hospital
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven
city: Liège
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Calgary
country: Canada
facility: University of Calgary
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba
state: Manitoba
city: Toronto
country: Canada
facility: Toronto General Hospital
state: Ontario
city: Amiens
country: France
facility: CHU Amiens Picardie
city: Angers
country: France
facility: CHU Angers
city: Besançon
country: France
facility: Hôpital Jean Minjoz
city: Caen
country: France
facility: C.H.U. de Caen
city: Créteil
country: France
facility: CHU henri Mondor
city: La Tronche
country: France
facility: CHU de Grenoble- Hopital Michallon
city: Lille
country: France
facility: CHRU de Lille
city: Lyon
country: France
facility: Hôpital de la Croix Rousse
city: Paris
country: France
facility: Hopital La Pitie Salpetriere
city: Villejuif
country: France
facility: Hopital Paul Brousse
city: Zurich
country: Switzerland
facility: University of Zurich
city: Brighton
country: United Kingdom
facility: Brighton & Sussex University Hospitals NHS Trust
city: Hull
country: United Kingdom
facility: Hull and East Yorkshire Hospitals NHS Trust
city: Liverpool
country: United Kingdom
facility: Royal Liverpool & Broadgreen University Hospitals NHS Trust
city: London
country: United Kingdom
facility: Barts Health NHS Trust
city: London
country: United Kingdom
facility: Chelsea and Westminster Hospital
city: London
country: United Kingdom
facility: Imperial College
city: London
country: United Kingdom
facility: Kings College Hospital NHS Trust
city: Newcastle
country: United Kingdom
facility: Freeman Hospital
city: Nottingham
country: United Kingdom
facility: Nottingham University Hospitals NHS Trust
city: Plymouth
country: United Kingdom
facility: Derriford Hospital
city: Portsmouth
country: United Kingdom
facility: Portsmouth Hospitals NHS Trust
Study officials:
affiliation: Gilead Sciences
name: Gilead Study Director
role: STUDY_DIRECTOR
References: