Liver Diseases, Alcoholic
Conditions
Keywords
GSK4532990, Alcohol-related liver disease, Steatohepatitis
Brief summary
The goal of this study is to assess the safety and efficacy of GSK4532990 in participants with alcohol-related liver disease.
Interventions
DRUGGSK4532990
GSK4532990 will be administered
DRUGPlacebo
Placebo will be administered
Sponsors
GlaxoSmithKline
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Capable of giving signed informed consent prior to the performance of any study-specific procedures. * Able and willing to comply with all study assessments and adhere to the protocol schedule of activities. * In the opinion of the investigator, there is a history of alcohol consumption compatible with either ALD or Met ALD. * A female participant is eligible to participate after meeting additional pre-defined criteria. * Participants must meet predefined stable use requirements of concomitant medications based on study criteria. * Participant has advanced chronic liver disease
Exclusion criteria
* Meeting any definition of organ system failure as defined by the North American Consortium for Study of End-stage Liver Disease (NACSELD) * Exceeding pre-defined biochemical parameters for Alanine Aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline Phosphatase (ALP), Platelets, International normalised ratio (INR), Albumin, estimated glomerular filtration rate (eGFR), Urine albumin-creatinine ratio (UACR) or Glycosylated Hemoglobin (HbA1c). Other primary causes of liver disease based on study criteria. * Current malignancy (except for basal cell carcinoma or uterine carcinoma-in-situ) at screening. Participants under evaluation for possible malignancy at screening are not eligible. * Prior organ transplant or current listing or active consideration for organ transplant during the screening period (except for corneal transplants). * Chronic or acute, including partial, known portal vein thrombosis. * Prior transjugular intrahepatic portosystemic shunt (TIPSS) insertion. * Any acute cardiovascular event including myocardial infarction, unstable angina, symptomatic heart failure, or cerebrovascular accident in the 6 months prior to screening. * Poorly controlled hypertension * Clinical suspicion of rhabdomyolysis during the screening period * Clinical suspicion of a bleeding episode during the screening period related to portal hypertension and/or low blood fibrinogen level. * Body Mass Index (BMI) \>35 kg/m2 at screening * Any liver-related clinical event that started (onset) \<8 weeks prior to Baseline (D1).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Up to 8 weeks | — |
| Number of participants with potentially clinically relevant changes in electrocardiogram (ECG), vital signs, and clinical laboratory tests | Up to 8 weeks | — |
| Change from baseline in Liver Stiffness measurement (LSM) reduction using FibroScan® at Week 52 (kiloPascal) | Baseline (Day 1) and up to Week 52 | Liver stiffness will be measured by vibration-controlled transient elastography (VCTE) using the FibroScan® device. |
| Change from baseline in model for end-stage liver disease (MELD) score reduction at Week 52 | Baseline (Day 1) and up to Week 52 | MELD is a scoring system for assessing the severity of chronic liver disease. MELD scores range between 6 and 40, with 40 being the most severe. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum plasma concentration (Cmax) of GSK4532990 | Up to Day 4 | — |
| Area Under the Curve from Time 0 to t [AUC (0-t)] of GSK4532990 | Up to Day 4 | — |
| Area Under the Curve from Time 0 to 24 hours [AUC (0-24)] of GSK4532990 | Up to 24 hours | — |
| Plasma half-life (t1/2) of GSK4532990 | Up to Day 4 | — |
| Apparent clearance (CL/F) of GSK4532990 | Up to Day 4 | — |
| Time to maximum concentration (tmax) of GSK4532990 | Up to Day 4 | — |
| Apparent terminal phase volume of distribution (Vz/F) of GSK4532990 | Up to Day 4 | — |
| Change from baseline in serum AST at Week 52 | Baseline (Day 1), and at Week 52 | — |
| Change from baseline in Enhanced Liver Fibrosis (ELF™) score at Week 52 | Baseline (Day 1), and at Week 52 | The ELF™ score will be calculated using a published algorithm combining the values of a set of extracellular matrix markers, including tissue inhibitor of metalloproteinases-1 (TIMP-1), type III procollagen (PIIINP), and hyaluronic acid (HA). The ELF™ score is used as a prognostic marker for disease progression. ELF™ score will range between 4.5 to 14.7. A higher ELF™ score will predict worse prognosis |
| Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 | Up to Day 3 | — |
| Maximum observed plasma concentration (Cmax) of GSK4532990 | Up to Day 3 | — |
Countries
Argentina, Australia, Canada, Denmark, France, Germany, Greece, Italy, Japan, Mexico, Poland, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), United Kingdom, United States
Contacts
CONTACTUS GSK Clinical Trials Call Center
CONTACTEU GSK Clinical Trials Call Center
Outcome results
None listed