Clinical trial NCT04620148: TAK-242 in Patients With Acute Alcoholic Hepatitis
Official title: 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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Acute-On-Chronic Liver Failure
Lead sponsor: Akaza Bioscience Ltd
Sponsor class: INDUSTRY
Collaborators: name: Iqvia Pty Ltd
First posted: 2020-11-06
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in CLIF-C ACLF score from baseline to Day 8
timeFrame: Baseline to Day 8
Secondary outcomes:
measure: Percentage of subjects who experience at least 1 markedly abnormal treatment-emergent AE or SAE
timeFrame: To Day 28
measure: 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
timeFrame: To Day 28
measure: Percentage of subjects who discontinue study drug due to an AE
timeFrame: To Day 28
measure: Change in naturally log-transformed key biomarkers
timeFrame: Baseline to day 8
measure: Survival at Day 28 after initiation of TAK-242 therapy versus placebo
timeFrame: Baseline to Day 28
Other outcomes:
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