TAK-242 in Patients With Acute Alcoholic Hepatitis

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Acute-On-Chronic Liver Failure
• Intervention / Treatment: Drug: TAK-242; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 100
• Phase: Phase 2

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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	Drug: TAK-242; TAK-242 concentrate solution 80 mg/mL for dilution and infusion
Placebo Comparator: 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	Drug: Placebo; Matching placebo concentrate solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in CLIF-C ACLF score from baseline to Day 8	Baseline to Day 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
Percentage of subjects who discontinue study drug due to an AE		To Day 28
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
Survival at Day 28 after initiation of TAK-242 therapy versus placebo		Baseline to Day 28

Collaborators and Investigators

• Sponsor: Akaza Bioscience Ltd
• Collaborators: IQVIA Pty Ltd

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2021
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): December 1, 2022

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 3, 2020
• First Posted (Actual): November 6, 2020

Study Record Updates

• Last Update Posted (Actual): August 2, 2021
• Last Update Submitted That Met QC Criteria: July 30, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Digestive System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Liver Diseases; Liver Failure, Acute; Hepatitis; Liver Diseases, Alcoholic; Alcohol-Induced Disorders; End Stage Liver Disease; Liver Failure; Hepatic Insufficiency; Acute-On-Chronic Liver Failure; Hepatitis, Alcoholic
• Other Study ID Numbers: TAK-242-2001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No