A Study to Investigate the Safety and Efficacy of GSK4532990 Compared With Placebo in Adult Participants Aged 18 to 70 Years With Alcohol-related Liver Disease

Official title

A Dose-Finding, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of GSK4532990 for Steatohepatitis in Adults With Alcohol-related Liver Disease (ALD)

Overview

The goal of this study is to assess the safety and efficacy of GSK4532990 in participants with alcohol-related liver disease.

Interventions

• Drug GSK4532990
  GSK4532990 will be administered
• Drug Placebo
  Placebo will be administered

Primary outcome measures

• Number of participants with adverse events (AEs) and serious adverse events (SAEs) [Time frame: Up to 8 weeks]
• Number of participants with potentially clinically relevant changes in electrocardiogram (ECG), vital signs, and clinical laboratory tests [Time frame: Up to 8 weeks]
• Change from baseline in Liver Stiffness measurement (LSM) reduction using FibroScan® at Week 52 (kiloPascal) [Time frame: Baseline (Day 1) and up to Week 52]
• Change from baseline in model for end-stage liver disease (MELD) score reduction at Week 52 [Time frame: Baseline (Day 1) and up to Week 52]

Secondary outcome measures (11)

• Maximum plasma concentration (Cmax) of GSK4532990 [Time frame: Up to Day 4]
• Area Under the Curve from Time 0 to t [AUC (0-t)] of GSK4532990 [Time frame: Up to Day 4]
• Area Under the Curve from Time 0 to 24 hours [AUC (0-24)] of GSK4532990 [Time frame: Up to 24 hours]
• Plasma half-life (t1/2) of GSK4532990 [Time frame: Up to Day 4]
• Apparent clearance (CL/F) of GSK4532990 [Time frame: Up to Day 4]
• Time to maximum concentration (tmax) of GSK4532990 [Time frame: Up to Day 4]
• Apparent terminal phase volume of distribution (Vz/F) of GSK4532990 [Time frame: Up to Day 4]
• Change from baseline in serum AST at Week 52 [Time frame: Baseline (Day 1), and at Week 52]
• Change from baseline in Enhanced Liver Fibrosis (ELF™) score at Week 52 [Time frame: Baseline (Day 1), and at Week 52]
• Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 [Time frame: Up to Day 3]
• Maximum observed plasma concentration (Cmax) of GSK4532990 [Time frame: Up to Day 3]

Eligibility criteria

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).

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

United States · 34 centers

• GSK Investigational Site — Chandler
• GSK Investigational Site — Phoenix
• GSK Investigational Site — Tucson
• GSK Investigational Site — Tucson
• GSK Investigational Site — Coronado
• GSK Investigational Site — Lancaster
• GSK Investigational Site — Los Angeles
• GSK Investigational Site — Los Angeles
• … and 26 more centers

Japan · 14 centers

Center list to be confirmed — check the primary protocol.

Spain · 12 centers

Center list to be confirmed — check the primary protocol.

Argentina · 9 centers

• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Buenos Aires
• GSK Investigational Site — Ciudad AutOnoma de Buenos Aire
• GSK Investigational Site — Ciudad Autonoma de Buenos Aire
• GSK Investigational Site — Rosario
• GSK Investigational Site — Rosario
• … and 1 more center

Italy · 9 centers

• GSK Investigational Site — Bergamo
• GSK Investigational Site — Bologna
• GSK Investigational Site — Messina
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• GSK Investigational Site — Milan
• … and 3 more centers

United Kingdom · 9 centers

Center list to be confirmed — check the primary protocol.

Canada · 8 centers

• GSK Investigational Site — Calgary
• GSK Investigational Site — New Westminster
• GSK Investigational Site — Vancouver
• GSK Investigational Site — London
• GSK Investigational Site — Toronto
• GSK Investigational Site — Toronto
• GSK Investigational Site — Montreal
• GSK Investigational Site — Terrebonne

South Korea · 8 centers

Center list to be confirmed — check the primary protocol.

France · 6 centers

• GSK Investigational Site — Angers
• GSK Investigational Site — Bobigny
• GSK Investigational Site — Créteil
• GSK Investigational Site — Lille
• GSK Investigational Site — Montpellier
• GSK Investigational Site — Rouen

Germany · 6 centers

• GSK Investigational Site — Bochum
• GSK Investigational Site — Berlin
• GSK Investigational Site — Berlin
• GSK Investigational Site — Kiel
• GSK Investigational Site — Leipzig
• GSK Investigational Site — Mainz

Australia · 5 centers

• GSK Investigational Site — Adelaide
• GSK Investigational Site — Melbourne
• GSK Investigational Site — Parkville Melbourne
• GSK Investigational Site — Murdoch
• GSK Investigational Site — Perth

Turkey (Türkiye) · 4 centers

Center list to be confirmed — check the primary protocol.

Denmark · 3 centers

• GSK Investigational Site — Esbjerg
• GSK Investigational Site — Hvidovre
• GSK Investigational Site — Odense C

Greece · 3 centers

• GSK Investigational Site — Athens
• GSK Investigational Site — Athens
• GSK Investigational Site — Athens

Mexico · 3 centers

Center list to be confirmed — check the primary protocol.

Poland · 3 centers

Center list to be confirmed — check the primary protocol.

South Africa · 2 centers

Center list to be confirmed — check the primary protocol.

Sweden · 2 centers

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT06613698 · 222291 · 2024-511596-15

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗