TAK-242 in Patients With Acute Alcoholic Hepatitis

Acute-On-Chronic Liver Failure Clinical Trial

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04620148
• Other study ID #: TAK-242-2001
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: December 2021
• Est. completion date: December 2022

Study information

• Verified date: July 2021
• Source: Akaza Bioscience Ltd
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 100
• Est. completion date: December 2022
• Est. primary completion date: December 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acute-On-Chronic Liver Failure
• End Stage Liver Disease
• Hepatic Insufficiency
• Hepatitis, Alcoholic
• Liver Failure

Intervention

Drug:
• TAK-242
TAK-242 concentrate solution 80 mg/mL for dilution and infusion
• Placebo
Matching placebo concentrate solution

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Akaza Bioscience Ltd	Iqvia Pty Ltd

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in CLIF-C ACLF score from baseline to Day 8		Baseline to Day 8
Secondary	Percentage of subjects who experience at least 1 markedly abnormal treatment-emergent AE or SAE	The percentage of subjects who experience at least 1 treatment-emergent AE or SAE that meets the Sponsor's markedly abnormal criteria	To Day 28
Secondary	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	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	To Day 28
Secondary	Percentage of subjects who discontinue study drug due to an AE		To Day 28
Secondary	Change in naturally log-transformed key biomarkers	Change in naturally log-transformed key biomarkers (TB, IL-8, high sensitivity CRP [hs-CRP], and urinary NGAL)	Baseline to day 8
Secondary	Survival at Day 28 after initiation of TAK-242 therapy versus placebo		Baseline to Day 28