Acute Alcoholic Hepatitis Causing Decompensation of Alcohol related Cirrhosis and Acute-on-Chronic Liver Failure MedDRA version: 20.1 Level: PT Classification code 10001627 Term: Alcoholic liver disease System Organ Class: 10019805 - Hepatobiliary disorders
Conditions
Sponsors
Akaza Bioscience Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. In the opinion of the investigator, the subject is deemed capable of understanding and complying with protocol requirements. If the subject is deemed incapable because of encephalopathy, then informed consent can be signed by a representative of the subject, in line with local law and regulation. 2. The subject or the subject's representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures. 3. The subject is male or female =18 and 20 mg/dL at diagnosis); OR criteria of AKI Stage 1b or 2 (Appendix M) after initial supportive treatment with fluids, albumin, or terlipressin; AND the CLIF-C ACLF score is >35 and 40 gm alcohol/day in women and >60 gm alcohol/day in men) for >6 months with =65 years) yes F.1.3.1 Number of subjects for this age range 25
Exclusion criteria
Exclusion criteria: 1.Subject has been hospitalized for more than 10 days 2.Subject has received any investigational compound within 30 days prior to the first dose of study drug or is scheduled to receive another investigational drug or device in the course of the study. Concomitant observational studies are allowed 3.Subject has received TAK-242 in a previous clinical study. 4.Subject has received corticosteroids for alcohol-induced liver failure within the 4 weeks prior to randomization. 5.Subject has cirrhosis from other chronic causes including nonalcoholic steatohepatitis (NASH), hepa titis C virus (HCV), primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC), hemochromatosis, alpha-1-antitrypsin deficiency, or Wilson’s disease. 6. The subject has tested positive for SARS-CoV-2 infection within 7 days prior to randomization and administration of study drug. 7.Subject has a medical history of co-infection with HIV, HBV, HCV, or HEV. Subjects with a previous diagnosis of hepatitis C treated with a documented course of an approved antiviral therapy for HCV who have achieved a sustained virologic response may be enrolled. 8.Subject has proven untreated gram-positive bacterial infection including sepsis, bacterial peritonitis, pneumonia, cellulitis, septic arthritis, osteomyelitis or other gram-positive infection. These patients can be included once they are culture negative. 9.Subject has evidence of untreated infection, including gram negative infection. If a subject has 1 or more underlying infections, he or she may be entered into the study provided that he or she is clinically responding to treatment as judged by clinical and laboratory assessments. Subjects with chronic infections will be excluded. 10.Subject has acute or subacute liver failure without underlying cirrhosis. 11.Subject has medical history of liver failure due to other causes, including, but not limited, to autoimmune hepatitis, PBC and PSC, drug-induced liver injury, and infections causing liver damage. 12.Subject has atypical laboratory screening tests including AST or ALT >400 IU/L, AST:ALT ratio 400 IU/mL unless a liver biopsy has confirmed the diagnosis of AH. 13.Subject has a history of liver transplant. 14.Subject has developed decompensation at any time in the postoperative period following partial hepatectomy. 15.Subject has clinically significant hemolysis or DIC 16.Subject has chronic and/or pre-existing kidney disease defined as estimated glomerular filtration rate (eGFR) 40 mmHg] persisting despite adequate fluid resuscitation). No subjects who require vasopressors to maintain a MAP >70 mmHg will be randomized. Patients on treatment with terlipressin for the treatment of AKI can be included. 20.Subject has evidence of significant and/or uncontrolled bleeding. Patients with gastrointestinal bleeding can be enrolled 48 hours after the bleeding has been controlled, as demonstrated by stable hemoglobin and hematocrit and
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of this study will be to investigate the effect of intravenous (IV) TAK-242 administered for 7 days in subjects with cirrhosis due to alcoholic liver disease (ALD), and superimposed AH resulting in Grade 1 or 2 ACLF on the Chronic Liver Failure Consortium (CLIF-C) ACLF score.;Secondary Objective: To investigate the safety of IV TAK-242 administered for 7 days in subjects with Grade 1 or 2 ACLF. To investigate the effects of IV TAK-242 administered for 7 days in subjects with Grade 1 or 2 ACLF on key biomarkers including IL-8, creactive protein (CRP), total bilirubin (TB), and urine neutrophil gelatinase-associated lipocalin (NGAL). To investigate the effect of IV TAK-242 administered for 7 days in subjects with Grade 1 or 2 ACLF on Day 28 survival. ;Primary end point(s): Change in CLIF-C ACLF score from baseline to Day 8.;Timepoint(s) of evaluation of this end point: baseline to Day 8. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The percentage of subjects who experience at least 1 treatment-emergent AE (TEAE) or SAE. • The percentage of subjects who discontinue the study drug due to an AE (including methemoglobinemia). • The percentage of subjects who experience at least 1 treatment-emergent clinical laboratory test result or abnormal ECG that meets the Akaza Bioscience Limited markedly abnormal criteria. • Change in naturally log-transformed key biomarkers (TB, IL-8, high sensitivity CRP (hs CRP), M30, and urinary NGAL) from baseline to Day 8. • Survival at Day 28 after the initiation of TAK-242 therapy versus placebo. ;Timepoint(s) of evaluation of this end point: • LPLV • Day 8 • LPLV • baseline to Day 8 • baseline to Day 28 | — |
Countries
France, Germany, Hungary, United Kingdom
Outcome results
None listed