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
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 | Description |
|---|---|---|
| Change in CLIF-C Acute-on-chronic Liver Failure (CLIF-C ACLF) Score From Baseline to Day 8 | Baseline to Day 8 | The CLIF-C ACLF score is a prognostic tool used for patients with acute-on-chronic liver failure (ACLF) to predict 28-day and 90-day mortality, with scores ranging from 0 to 100. A higher score indicates higher mortality risk: a score of \<40 represents a lower risk, while a score ≥70 indicates a very high risk. |
Countries
United Kingdom
Participant flow
Recruitment details
A total of 60 to 100 subjects were to be enrolled, 4 subjects consented to participate, and 3 subjects were randomized.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 1 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age, Continuous | 55 Years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United Kingdom | 3 participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 3 | 0 / 0 |
| other Total, other adverse events | 0 / 3 | 0 / 0 |
| serious Total, serious adverse events | 2 / 3 | 0 / 0 |
Outcome results
None listed