TAK-242 in Patients With Acute Alcoholic Hepatitis
- Registration Number
- NCT04620148
- Lead Sponsor
- Akaza Bioscience Ltd
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- UNKNOWN
- Sex
- All
- Target Recruitment
- 100
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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description TAK-242 TAK-242 Patients will be administered TAK-242 as a continuous IV infusion with standard care starting with a loading dose of 0.9 mg/kg administered over 30 minutes, followed by a continuous, constant rate infusion of 1.8 mg/kg/day for 7 days Placebo Placebo Patients will be administered placebo as a continuous IV infusion with standard care starting with a loading dose of 0.9 mg/kg administered over 30 minutes, followed by a continuous, constant rate infusion of 1.8 mg/kg/day for 7 days
- Primary Outcome Measures
Name Time Method Change in CLIF-C ACLF score from baseline to Day 8 Baseline to Day 8
- Secondary Outcome Measures
Name Time Method Percentage of subjects who experience at least 1 markedly abnormal treatment-emergent AE or SAE To Day 28 The percentage of subjects who experience at least 1 treatment-emergent AE or SAE that meets the Sponsor's markedly abnormal criteria
Percentage of subjects who experience at least 1 treatment-emergent clinical laboratory test result or abnormal ECG that meets the Sponsor's markedly abnormal criteria To Day 28 The percentage of subjects who experience at least 1 treatment-emergent clinical laboratory test result or abnormal ECG that meets the Sponsor's markedly abnormal criteria
Percentage of subjects who discontinue study drug due to an AE To Day 28 Change in naturally log-transformed key biomarkers Baseline to day 8 Change in naturally log-transformed key biomarkers (TB, IL-8, high sensitivity CRP \[hs-CRP\], and urinary NGAL)
Survival at Day 28 after initiation of TAK-242 therapy versus placebo Baseline to Day 28