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

Recruiting

• Conditions: Liver Diseases, Alcoholic
• Interventions: Drug: GSK4532990; 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

Study Timeline

• Study First Submitted: 2024-09-23
• Study First Submitted QC: 2024-09-23
• Study First Posted: 2024-09-26
• Study Start: 2024-09-27
• Status Verified: 2025-06
• Last Update Submitted: 2025-06-13
• Last Update Posted: 2025-06-18
• Primary Completion: 2026-12-08
• Study Completion: 2027-08-23

Recruitment & Eligibility

• Status: 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 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).

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 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.
Number of participants with adverse events (AEs) and serious adverse events (SAEs)	Up to 8 weeks

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; 🇬🇧 London, United Kingdom