TAK-242 in Patients With Acute Alcoholic Hepatitis

• Sponsor: Akaza Bioscience Ltd (Industry)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT04620148
• Collaborator: Iqvia Pty Ltd (Industry)
• Enrollment: 100
• Arms: 2
• Anticipated Duration (Months): 12

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Acute-On-Chronic Liver Failure	Drug: TAK-242; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Anticipated Enrollment: 100 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• 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
• Anticipated Study Start Date: Dec 1, 2021
• Anticipated Primary Completion Date: Dec 1, 2022
• Anticipated Study Completion Date: Dec 1, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in CLIF-C ACLF score from baseline to Day 8 [Baseline to Day 8]

Secondary Outcome Measures

1. 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

2. 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

3. Percentage of subjects who discontinue study drug due to an AE [To Day 28]

4. 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)

5. Survival at Day 28 after initiation of TAK-242 therapy versus placebo [Baseline to Day 28]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Akaza Bioscience Ltd
• Iqvia Pty Ltd

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Akaza Bioscience Ltd
• ClinicalTrials.gov Identifier: NCT04620148
• Other Study ID Numbers: TAK-242-2001
• First Posted: Nov 6, 2020
• Last Update Posted: Aug 2, 2021
• Last Verified: Jul 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Liver Failure; Hepatic Insufficiency; End Stage Liver Disease; Acute-On-Chronic Liver Failure; Hepatitis, Alcoholic

Study Results

No Results Posted as of Aug 2, 2021