Phase 2b Study of GSK4532990 in Adults With NASH
- Conditions
- Nonalcoholic Fatty Liver DiseaseNon-alcoholic Fatty Liver Disease
- Interventions
- Drug: Placebo
- Registration Number
- NCT05583344
- Lead Sponsor
- GlaxoSmithKline
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 284
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - High Dose GSK4532990 GSK4532990 - Low Dose GSK4532990 GSK4532990 -
- Primary Outcome Measures
Name Time Method Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - F3 Cohort At Week 52 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.
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - F3 Cohort At Week 52 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.
- Secondary Outcome Measures
Name Time Method Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - Pooled Cohort (F3 participants and F4 participants) At Week 52 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.
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - Pooled Cohort (F3 participants and F4 participants) At Week 52 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.
Change from baseline in Pro-peptide of type III collagen (Pro-C3) - F3 Cohort 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 Baseline (Day 1) and at Week 24 and 52 Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - F3 Cohort 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 Baseline (Day 1) and at Week 24 and 52 Change from baseline in Enhanced Liver Fibrosis (ELF) Score - F3 Cohort Baseline (Day 1) and at Week 24 and 52 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.
Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort At Week 52 Change from baseline in Pro-peptide of type III collagen (Pro-C3) - Pooled Cohort (F3 participants and F4 participants) 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) Baseline (Day 1) and at Week 24 and 52 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.
Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24- F3 Cohort At Week 24 Change from baseline in liver fat using Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) - Pooled Cohort (F3 participants and F4 participants) 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) 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 52 - Pooled Cohort (F3 participants and F4 participants) At Week 52 Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F3 Cohort Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Temperature (Celsius) - F3 Cohort Baseline (Day 1) and up to Week 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) At Week 24 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) Baseline (Day 1) and at Week 24 and 52 Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F3 Cohort Up to Week 66 Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F3 Cohort Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F3 Cohort Baseline (Day 1) and up to Week 52 Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F3 Cohort Baseline (Day 1) and up to Week 52 Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F4 Cohort Up to Week 66 Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F4 Cohort Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Temperature (Celsius) - F4 Cohort Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F4 Cohort Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F4 Cohort Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - Pooled Cohort (F3 participants and F4 participants) Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - Pooled Cohort (F3 participants and F4 participants) Baseline (Day 1) and up to Week 52 Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F4 Cohort Baseline (Day 1) and up to Week 52 Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - Pooled Cohort (F3 participants and F4 participants) Up to Week 66 Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - Pooled Cohort (F3 participants and F4 participants) Baseline (Day 1) and up to Week 52 Change from Baseline in Vital Signs - Temperature (Celsius) - Pooled Cohort (F3 participants and F4 participants) Baseline (Day 1) and up to Week 52 Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - Pooled Cohort (F3 participants and F4 participants) Baseline (Day 1) and up to Week 52 Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F3 Cohort Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose Maximum observed concentration (Cmax) of GSK4532990- F3 Cohort Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F3 Cohort Up to Week 52 Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F4 Cohort Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose Maximum observed concentration (Cmax) of GSK4532990- F4 Cohort Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F4 Cohort Up to Week 52
Trial Locations
- Locations (1)
GSK Investigational Site
🇬🇧Nottingham, United Kingdom