A Study to Investigate the Safety and Efficacy of GSK4532990 Compared With Placebo in Adult Participants Aged 18 to 65 Years With Alcohol-related Liver Disease
Phase 2
Not yet recruiting
- Conditions
- Liver Diseases, Alcoholic
- Interventions
- Drug: Placebo
- Registration Number
- NCT06613698
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
The goal of this study is to assess the safety and efficacy of GSK4532990 in participants with alcohol-related liver disease.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 393
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.
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 or ongoing 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 liver transplant or current listing for liver transplant during the screening period.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description GSK4532990 Dose 1 GSK4532990 - GSK4532990 Dose 2 GSK4532990 - GSK4532990 Dose 3 GSK4532990 - GSK4532990 Dose 4 GSK4532990 - Placebo Placebo -
- Primary Outcome Measures
Name Time Method 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 28 (kiloPascal) Baseline (Day 1) and up to Week 28 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 28 Baseline (Day 1) and up to Week 28 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 Outcome Measures
Name Time Method 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 28 Baseline (Day 1), and at Week28 Change from baseline in Enhanced Liver Fibrosis (ELF™) score at Week 28 Baseline (Day 1), and at Week 28 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
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Middlesbrough, United Kingdom