Phase II, Double-blind, Randomized, Placebo-controlled, Multicentre Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of TAK-242 and (G-CSF) in Subjects With (sAH) and (ACLF)
The purpose of this research is to know if a new combination of drugs (TAK-242 and G-CSF) in combination with standard therapy for acute-on-chronic liver failure (ACLF) is more effective than standard therapy for ACLF treatment and is safe. Description of the population to be studied: ACLF is a syndrome that occurs in patients with chronic liver disease, with or without previously diagnosed cirrhosis, which is characterized by acute hepatic decompensation. Cirrhosis is a chronic disease of the liver marked by degeneration of cells, inflammation, and thickening and scarring (fibrosis) of liver tissue. Hepatic decompensation is a sudden decline in liver function. It is characterized by severe liver damage and complications like jaundice (yellowing of the skin or whites of the eyes), ascites (a condition where excess fluid accumulates in the abdominal cavity and in abdominal organs) and encephalopathy (a group of symptoms that result from damage or dysfunction in the brain, causing a range of cognitive and neurological impairments). It may result in liver failure, one or more organ failures other than liver (renal, brain, coagulation, respiratory, cardiovascular), and is associated with increased mortality within 28-days and up to 3 months from onset. Grade 1 ACLF has a \>15% risk of mortality at 28 days. Purpose of the study: The investigational medication, TAK-242, is aimed at stopping an over-reaction of the immune system (the body's defense system) while G-CSF encourages your liver cells to grow. In patients with severe inflammation of the liver due to alcohol \[severe alcoholic hepatitis (sAH)\] and ACLF, this over-reaction may cause the liver and other organs in the body to suddenly stop working (organ failure). The hypothesis of the study is that by blocking this over-reaction and encouraging your liver cells to grow your condition may improve.
• Patients accepted for inclusion into the study must meet all of the following criteria:
‣ Male and female subjects ≥18 of age and ≤75 years of age
⁃ Compliance with acceptable contraceptive methods.
⁃ With a diagnosis of severe alcoholic hepatitis that is resistant to steroid therapy as defined by a Lille score of \>0.45 and/or in whom steroids are contraindicated.
⁃ Eligible subjects will have Grade 1-3 ACLF with a maximum of three organ failures using the CLIF-C OF score AND the CLIF-C ACLF-CRP score of \>35 and \<60.