TAK-242 in Patients With Acute Alcoholic Hepatitis

A Randomized, Double-Blind, Placebo-Controlled, Multicenter, Proof-of-Concept, Phase 2a Study to Evaluate the Efficacy, Safety, Pharmacokinetics, and Pharmacodynamics of Intravenous TAK-242 in Subjects With Acute Alcoholic Hepatitis Causing Decompensation of Alcohol-related Cirrhosis and Acute-on-Chronic Liver Failure

A phase 2a double-blind, randomized, placebo-controlled, multicenter, proof-of-concept study to evaluate the efficacy, safety, pharmacokinetics, and pharmacodynamics of TAK-242 in subjects with acute decompensation of alcohol-related cirrhosis due to alcoholic hepatitis resulting in acute-on-chronic liver failure.

Inclusion Criteria:

• History of alcohol-related cirrhosis who continue to drink heavily
• History of an acute decompensating event with a clinical and/or liver biopsy diagnosis of alcoholic hepatitis
• Grade 1 or 2 ACLF using the CLIF-C OF score; OR bilirubin criteria OR criteria of acute kidney injury Stage 1b or 2 after initial supportive treatment with fluids, albumin, or terlipressin; AND CLIF-C ACLF score is >35 and <64
• History of alcohol-related cirrhosis based on clinical, radiological, and/or histological evidence

Exclusion Criteria:

• Received certain previous therapies (any investigational drug within 30 days of randomization, corticosteroids for alcohol-induced liver failure within 4 weeks of randomization, or received TAK-242 in any previous study)
• History of liver cirrhosis from other chronic diseases; liver failure from other causes
• History of liver transplantation, post-operative decompensation after partial hepatectomy, acute or subacute liver failure without underlying cirrhosis
• Any untreated infections including gram-positive infections, or active or latent atuberculosis, sepsis or septic shock, or coinfection with hepatitis B virus, hepatitis C virus, hepatitis E virus, or HIV
• Chronic or pre-existing kidney failure, uncontrolled medical disorder that might confound study results or compromise subject safety, oxygen saturation <90%, or requires mechanical ventilation.
• Uncorrected anemia, methemoglobinemia, disseminated intravascular coagulation, significant or uncontrolled bleeding, atypical laboratory screening tests.
• Uncontrolled seizures, Grade 3 or 4 hepatic encephalopathy, Creutzfeldt-Jakob disease, glucose-6-phosphate dehydrogenase deficiency.
• Active extrahepatic malignancy or survival prognosis of <6 months.