Phase 2b Study of GSK4532990 in Adults With NASH

Phase 2Active Not RecruitingNCT05583344

GlaxoSmithKline284 enrolled

Overview

The purpose of this study is to measure improvements in liver fibrosis and inflammation with GSK4532990 compared with placebo in participants with NASH and advanced fibrosis on biopsy (F3 or F4). The study duration will be up to 76 weeks including the screening period. The treatment duration will be up to 52 weeks.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

284

Conditions

Nonalcoholic Fatty Liver Disease Non-alcoholic Fatty Liver Disease

Interventions

GSK4532990DRUG

GSK4532990 will be administered.

PlaceboDRUG

Placebo will be administered.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Body Mass Index (BMI) ≥25 kilogram per meter square (kg/m\^2) (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m2 at Screening. * In the opinion of the investigator, there are features of metabolic syndrome and NAFLD is the most likely cause of liver disease. Metabolic syndrome may include type 2 diabetes mellitus (T2DM), obesity, dyslipidemia and hypertension. * A liver biopsy at baseline showing NAFLD Activity Score (NAS) \>=4 with at least 1 point each in steatosis, inflammation and ballooning and either Fibrosis 3 or Fibrosis 4 using NASH CRN Scoring System. * Able and willing to comply with all study assessments, including a liver biopsy at Week 52. Exclusion Criteria: * Current alcohol consumption ≥14 standard drinks (24 units, 196 g ethanol) per week for females or ≥21 standard drinks (37 units, 294g ethanol) per week for males. * Weight reduction surgery or procedures (including gastric banding and intragastric balloon insertion) within 2 years of Screening 1 and/or planned during the study. * History of cancer within previous 2 years from Screening 1, except basal or squamous cell carcinoma of the skin or in situ cervical carcinoma or any other type of cancer which has been treated medically or surgically with curative outcome.

Locations (170)

Outcomes

Primary Outcomes

Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - F3 Cohort

Improvement in histological fibrosis is assessed with Clinical research network (CRN) Scoring. No worsening of NASH is defined as no increase in the NAFLD Activity Score (NAS) for steatosis, ballooning, or inflammation.

Time frame: At Week 52

Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - F3 Cohort

NASH resolution is defined as a ballooning score of 0 and an inflammation score of 0-1. No worsening of fibrosis is defined as no increase in CRN fibrosis score.

Time frame: At Week 52

Secondary Outcomes

Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - Pooled Cohort (F3 participants and F4 participants)

Time frame: At Week 52

Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - Pooled Cohort (F3 participants and F4 participants)

NASH resolution is defined as a ballooning score of 0 and an inflammation score of 0-1. No worsening of fibrosis is defined as no increase in CRN fibrosis score.

Time frame: At Week 52

Change from baseline in Pro-peptide of type III collagen (Pro-C3) - F3 Cohort

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - F3 Cohort

Data from ClinicalTrials.gov

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GSK Investigational Site

Homewood, Alabama, United States

GSK Investigational Site

Chandler, Arizona, United States

GSK Investigational Site

Chandler, Arizona, United States

GSK Investigational Site

Mesa, Arizona, United States

GSK Investigational Site

Jonesboro, Arkansas, United States

GSK Investigational Site

North Little Rock, Arkansas, United States

GSK Investigational Site

Huntington Park, California, United States

GSK Investigational Site

La Jolla, California, United States

GSK Investigational Site

Orange, California, United States

GSK Investigational Site

Poway, California, United States

...and 160 more locations

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in Liver stiffness measurement (LSM) by Vibration-controlled transient elastography (VCTE) - F3 Cohort

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in Enhanced Liver Fibrosis (ELF) Score - F3 Cohort

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 \< 9.8 : Low risk of progression, ELF score 9.8 to \< 11.3 : Moderate risk of progression and ELF score \> = 11.3 : High risk of progression.

Time frame: Baseline (Day 1) and at Week 24 and 52

Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24- F3 Cohort

Time frame: At Week 24

Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort

Time frame: At Week 52

Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - F3 Cohort

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in Pro-peptide of type III collagen (Pro-C3) - Pooled Cohort (F3 participants and F4 participants)

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - Pooled Cohort (F3 participants and F4 participants)

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in Liver stiffness measurement (LSM) by Vibration-controlled transient elastography (VCTE) - Pooled Cohort (F3 participants and F4 participants)

Time frame: Baseline (Day 1) and at Week 24 and 52

Change from baseline in Enhanced Liver Fibrosis (ELF) Score - Pooled Cohort (F3 participants and F4 participants)

Time frame: Baseline (Day 1) and at Week 24 and 52

Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24 - Pooled Cohort (F3 participants and F4 participants)

Time frame: At Week 24

Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - Pooled Cohort (F3 participants and F4 participants)

Time frame: At Week 52

Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - Pooled Cohort (F3 participants and F4 participants)

Time frame: Baseline (Day 1) and at Week 24 and 52

Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F3 Cohort

Time frame: Up to Week 66

Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F3 Cohort