Acute-On-Chronic Liver Failure
Conditions
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.
Interventions
DRUGTAK-242
TAK-242 concentrate solution 80 mg/mL for dilution and infusion
DRUGPlacebo
Matching placebo concentrate solution
Sponsors
Iqvia Pty Ltd
Akaza Bioscience Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in CLIF-C ACLF score from baseline to Day 8 | Baseline to Day 8 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 | 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 | Baseline to Day 28 | — |
Outcome results
None listed