Selonsertib in Combination With Prednisolone Versus Prednisolone Alone in Participants With Severe Alcoholic Hepatitis (AH)

Gilead Sciences

Status and phase: Completed; Phase 2

Conditions: Alcoholic Hepatitis (AH)

Treatments: Drug: Selonsertib; Drug: Placebo; Drug: Prednisolone

Study type: Interventional

Funder types: Industry

Identifiers

NCT02854631

GS-US-416-2124

2016-000821-37 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 104 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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104 participants in 2 patient groups, including a placebo group

Selonsertib + Prednisolone

Experimental group

Description:

Selonsertib + prednisolone for 28 days

Treatment:

Drug: Prednisolone

Drug: Selonsertib

Prednisolone

Placebo Comparator group

Description:

Selonsertib placebo + prednisolone for 28 days

Treatment:

Drug: Prednisolone

Drug: Placebo