Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)
Condition: Alcoholic Hepatitis (AH)
MeSH terms: Hepatitis A; Hepatitis; Hepatitis, Alcoholic
Intervention: Selonsertib; Prednisolone; Placebo
Intervention description: 18 mg tablet administered orally once daily; 40 mg (4 x 10 mg tablets) administered orally once daily; Selonsertib placebo tablet administered orally once daily
Intervention MeSH terms: Prednisolone; Selonsertib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 104.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Cirrhosis; Prednisone; Jaundice

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.