Back to resultsTAK-242 in Patients With Acute Alcoholic Hepatitis
Primary Purpose
Acute-On-Chronic Liver Failure
Status
Unknown status
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
TAK-242
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for 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.
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
TAK-242
Placebo
Arm Description
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
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
Outcomes
Primary Outcome Measures
Change in CLIF-C ACLF score from baseline to Day 8
Secondary Outcome Measures
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
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
Percentage of subjects who discontinue study drug due to an AE
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)
Survival at Day 28 after initiation of TAK-242 therapy versus placebo
Full Information
NCT ID
NCT04620148
First Posted
November 3, 2020
Last Updated
July 30, 2021
Sponsor
Akaza Bioscience Ltd
Collaborators
Iqvia Pty Ltd
1. Study Identification
Unique Protocol Identification Number
NCT04620148
Brief Title
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
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
December 2021 (Anticipated)
Primary Completion Date
December 2022 (Anticipated)
Study Completion Date
December 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Akaza Bioscience Ltd
Collaborators
Iqvia Pty Ltd
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Acute-On-Chronic Liver Failure
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
100 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
TAK-242
Arm Type
Experimental
Arm Description
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
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
TAK-242
Intervention Description
TAK-242 concentrate solution 80 mg/mL for dilution and infusion
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Matching placebo concentrate solution
Primary Outcome Measure Information:
Title
Change in CLIF-C ACLF score from baseline to Day 8
Time Frame
Baseline to Day 8
Secondary Outcome Measure Information:
Title
Percentage of subjects who experience at least 1 markedly abnormal treatment-emergent AE or SAE
Description
The percentage of subjects who experience at least 1 treatment-emergent AE or SAE that meets the Sponsor's markedly abnormal criteria
Time Frame
To Day 28
Title
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
Description
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
Time Frame
To Day 28
Title
Percentage of subjects who discontinue study drug due to an AE
Time Frame
To Day 28
Title
Change in naturally log-transformed key biomarkers
Description
Change in naturally log-transformed key biomarkers (TB, IL-8, high sensitivity CRP [hs-CRP], and urinary NGAL)
Time Frame
Baseline to day 8
Title
Survival at Day 28 after initiation of TAK-242 therapy versus placebo
Time Frame
Baseline to Day 28
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
TAK-242 in Patients With Acute Alcoholic Hepatitis
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