TAK-242 in Patients With Acute Alcoholic Hepatitis

NCT04620148 | Unknown Phase 2 DMC

• 1 other identifier: TAK-242-2001
• Study Type: interventional
• Target: 100
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute-On-Chronic Liver Failure

Outcome Measures

Primary Outcomes (1)

• Change in CLIF-C ACLF score from baseline to Day 8

  Baseline to Day 8

Secondary Outcomes (5)

• Percentage of subjects who experience at least 1 markedly abnormal treatment-emergent AE or SAE

  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

  To Day 28

• 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

• Survival at Day 28 after initiation of TAK-242 therapy versus placebo

  Baseline to Day 28

Study Arms (2)

TAK-242

EXPERIMENTAL

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

Placebo

PLACEBO COMPARATOR

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

Interventions

TAK-242 DRUG

TAK-242 concentrate solution 80 mg/mL for dilution and infusion

TAK-242

Placebo DRUG

Matching placebo concentrate solution

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Akaza Bioscience Ltd: lead
• Iqvia Pty Ltd: collaborator

MeSH Terms

Conditions

Acute-On-Chronic Liver Failure

Interventions

ethyl 6-(N-(2-chloro-4-fluorophenyl)sulfamoyl)cyclohex-1-ene-1-carboxylate

Condition Hierarchy (Ancestors)

Liver Failure, Acute; Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 6, 2020
• Study Start: December 1, 2021
• Primary Completion: December 1, 2022
• Study Completion: December 1, 2022
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share