Clinical trial NCT06613698: 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
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)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Liver Diseases, Alcoholic
Keywords: GSK4532990
Alcohol-related liver disease
Steatohepatitis
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2024-09-26
Enrollment: 393
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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


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.

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).

Primary outcomes:
measure: Number of participants with adverse events (AEs) and serious adverse events (SAEs)
timeFrame: Up to 8 weeks
measure: Number of participants with potentially clinically relevant changes in electrocardiogram (ECG), vital signs, and clinical laboratory tests
timeFrame: Up to 8 weeks
measure: Change from baseline in Liver Stiffness measurement (LSM) reduction using FibroScan® at Week 28 (kiloPascal)
timeFrame: Baseline (Day 1) and up to Week 28
measure: Change from baseline in model for end-stage liver disease (MELD) score reduction at Week 28
timeFrame: Baseline (Day 1) and up to Week 28
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) of GSK4532990
timeFrame: Up to Day 4
measure: Area Under the Curve from Time 0 to t [AUC (0-t)] of GSK4532990
timeFrame: Up to Day 4
measure: Area Under the Curve from Time 0 to 24 hours [AUC (0-24)] of GSK4532990
timeFrame: Up to 24 hours
measure: Plasma half-life (t1/2) of GSK4532990
timeFrame: Up to Day 4
measure: Apparent clearance (CL/F) of GSK4532990
timeFrame: Up to Day 4
measure: Time to maximum concentration (tmax) of GSK4532990
timeFrame: Up to Day 4
measure: Apparent terminal phase volume of distribution (Vz/F) of GSK4532990
timeFrame: Up to Day 4
measure: Change from baseline in serum AST at Week 28
timeFrame: Baseline (Day 1), and at Week28
measure: Change from baseline in Enhanced Liver Fibrosis (ELF™) score at Week 28
timeFrame: Baseline (Day 1), and at Week 28
measure: Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990
timeFrame: Up to Day 3
measure: Maximum observed plasma concentration (Cmax) of GSK4532990
timeFrame: Up to Day 3
Other outcomes:
Locations:
city: Chandler
country: United States
facility: GSK Investigational Site
state: Arizona
city: Los Angeles
country: United States
facility: GSK Investigational Site
state: California
city: Brandon
country: United States
facility: GSK Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: GSK Investigational Site
state: Florida
city: Indianapolis
country: United States
facility: GSK Investigational Site
state: Indiana
city: Marrero
country: United States
facility: GSK Investigational Site
state: Louisiana
city: Detroit
country: United States
facility: GSK Investigational Site
state: Michigan
city: Philadelphia
country: United States
facility: GSK Investigational Site
state: Pennsylvania
city: McAllen
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Terrebonne
country: Canada
facility: GSK Investigational Site
state: Quebec
city: Bergamo
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Chiba
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Ansan
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Suwon Gyeonggi-do
country: Korea, Republic of
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Leon
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Valencia
country: Spain
facility: GSK Investigational Site
city: Glasgow Strathclyde
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
Study officials:
References: