Last updated: 10/24/2025 15:30:10
Phase 2b Study of GSK4532990 in Adults with NASHHORIZON
GSK study ID
218672
Clinicaltrials.gov ID
EudraCT ID
EU CT Number
Trial status
Recruitment complete
Recruitment complete
Trial overview
Official title: 17 β-Hydroxysteroid Dehydrogenase type 13 Minimization for the treatment of NASH (HORIZON): A Double-Blind, Placebo-Controlled Phase 2b Study to Evaluate the Efficacy and Safety of GSK4532990 in Adults with Nonalcoholic Steatohepatitis
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH – F3 Cohort
Timeframe: At Week 52
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis – F3 Cohort
Timeframe: 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)
Timeframe: At Week 52
Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis – Pooled Cohort (F3 participants and F4 participants)
Timeframe: At Week 52
Change from baseline in Pro-peptide of type III collagen (Pro-C3) – F3 Cohort
Timeframe: 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
Timeframe: 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
Timeframe: Baseline (Day 1) and at Week 24 and 52
Change from baseline in Enhanced Liver Fibrosis (ELF) Score - F3 Cohort
Timeframe: 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
Timeframe: At Week 24
Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort
Timeframe: At Week 52
Change from Baseline in Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) and Gamma-glutamyl transferase (GGT) (Units Per Liter) - F3 Cohort
Timeframe: 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)
Timeframe: 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)
Timeframe: 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)
Timeframe: 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)
Timeframe: 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)
Timeframe: 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)
Timeframe: 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)
Timeframe: Baseline (Day 1) and at Week 24 and 52
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) – F3 Cohort
Timeframe: Up to Week 66
Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) – F3 Cohort
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Temperature (Celsius) – F3 Cohort
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Heart Rate (Beats per minute) – F3 Cohort
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) – F3 Cohort
Timeframe: 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
Timeframe: Baseline (Day 1) and up to Week 52
Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) – F4 Cohort
Timeframe: Up to Week 66
Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) – F4 Cohort
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Temperature (Celsius) – F4 Cohort
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Heart Rate (Beats per minute) – F4 Cohort
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) – F4 Cohort
Timeframe: 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
Timeframe: 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)
Timeframe: Up to Week 66
Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) – Pooled Cohort (F3 participants and F4 participants)
Timeframe: Baseline (Day 1) and up to Week 52
Change from Baseline in Vital Signs - Temperature (Celsius) – Pooled Cohort (F3 participants and F4 participants)
Timeframe: 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)
Timeframe: 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)
Timeframe: 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)
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: 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
Timeframe: Up to Week 52
Interventions:
Enrollment:
284
Primary completion date:
2026-10-02
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Not applicable
Medical condition
Nonalcoholic Fatty Liver Disease
Product
Not applicable
Collaborators
Not applicable
Study date(s)
January 2023 to April 2027
Type
Interventional
Phase
2
Participation criteria
Sex
Female & Male
Age
18 - 75 Years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion criteria
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.
Trial location(s)
Location
GSK Investigational Site
San Antonio, TX, United States, 78229
Status
Recruitment Complete
Location
GSK Investigational Site
Austin, TX, United States, 78757
Status
Recruitment Complete
Location
GSK Investigational Site
Georgetown, TX, United States, 78626
Status
Recruitment Complete
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Study documents
No study documents available.
Results overview
Study Results yet to be posted
Recruitment status
Recruitment complete
Actual primary completion date
Not applicable
Actual study completion date
Not applicable
Plain language summaries
Plain language summaries of clinical trial results for Phase 2-4 clinical trials that were initiated on or after January 2022 will be posted by GSK within one year following study completion.
Additional information about the trial
Additional information
Not applicable
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