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
Location
GSK Investigational Site
Athens, GA, United States, 30607
Status
Recruitment Complete
Location
GSK Investigational Site
Bastrop, LA, United States, 71220
Status
Recruitment Complete
Location
GSK Investigational Site
Bradenton, FL, United States, 34209
Status
Recruitment Complete
Location
GSK Investigational Site
Brownsville, TX, United States, 78520
Status
Recruitment Complete
Location
GSK Investigational Site
CLARKSVILLE, TN, United States, 37040
Status
Recruitment Complete
Location
GSK Investigational Site
Chandler, AZ, United States, 85224
Status
Recruitment Complete
Location
GSK Investigational Site
Chapel Hill, NC, United States, 27599
Status
Recruitment Complete
Location
GSK Investigational Site
Chesterfield, MO, United States, 48038
Status
Recruitment Complete
Location
GSK Investigational Site
Ciudad Autonoma de Bueno, Argentina, C1056ABJ
Status
Recruitment Complete
Location
GSK Investigational Site
Capital Federal, Argentina, C1181ACH
Status
Recruitment Complete
Location
GSK Investigational Site
Ciudad AutOnoma de Buenos Aire, Argentina, 1118
Status
Recruitment Complete
Location
GSK Investigational Site
Colorado Springs, CO, United States, 80907
Status
Recruitment Complete
Location
GSK Investigational Site
Dallas, TX, United States, 75203
Status
Recruitment Complete
Location
GSK Investigational Site
Durham, NC, United States, 27710
Status
Recruitment Complete
Location
GSK Investigational Site
Edinburg, TX, United States, 78539
Status
Recruitment Complete
Location
GSK Investigational Site
Hallandale Beach, FL, United States, 33009
Status
Study Complete
Location
GSK Investigational Site
Houston, TX, United States, 77909
Status
Recruitment Complete
Location
GSK Investigational Site
Indianapolis, IN, United States, 46202
Status
Recruitment Complete
Location
GSK Investigational Site
Lancaster, PA, United States, 17604-3200
Status
Recruitment Complete
Location
GSK Investigational Site
Marietta, GA, United States, 30060
Status
Recruitment Complete
Location
GSK Investigational Site
Marrero, LA, United States, 70072
Status
Recruitment Complete
Location
GSK Investigational Site
Marrero, LA, United States, 70006
Status
Recruitment Complete
Location
GSK Investigational Site
Miami Lakes, FL, United States, 33016
Status
Recruitment Complete
Location
GSK Investigational Site
Monroe, LA, United States, 71201
Status
Recruitment Complete
Location
GSK Investigational Site
Morehead City, NC, United States, 28557
Status
Study Complete
Location
GSK Investigational Site
New York, NY, United States, 10033
Status
Recruitment Complete
Location
GSK Investigational Site
NEWCASTLE UPON TYNE, United Kingdom, NE7 7DN
Status
Study Complete
Location
GSK Investigational Site
North Little Rock, AR, United States, 72117
Status
Recruitment Complete
Location
GSK Investigational Site
Orange, CA, United States, 92866
Status
Recruitment Complete
Location
GSK Investigational Site
Pittsburgh, PA, United States, 15213
Status
Recruitment Complete
Location
GSK Investigational Site
Richmond, VA, United States, 23236
Status
Recruitment Complete
Location
GSK Investigational Site
San Francisco, CA, United States, 94115
Status
Recruitment Complete
Location
GSK Investigational Site
Atlanta, GA, United States, 30328
Status
Recruitment Complete
Location
GSK Investigational Site
Shreveport, LA, United States, 71105
Status
Recruitment Complete
Location
GSK Investigational Site
Springboro, OH, United States, 45066
Status
Recruitment Complete
Location
GSK Investigational Site
Topeka, KS, United States, 66606
Status
Recruitment Complete
Location
GSK Investigational Site
Chandler, AZ, United States, 85712
Status
Recruitment Complete
Location
GSK Investigational Site
West Palm Beach, FL, United States, 33401
Status
Recruitment Complete
Location
GSK Investigational Site
Wyomissing, PA, United States, 19610
Status
Recruitment Complete
Location
GSK Investigational Site
Ypsilanti, MI, United States, 48197
Status
Recruitment Complete
Location
GSK Investigational Site
Sacramento, CA, United States, 95817
Status
Recruitment Complete
Location
GSK Investigational Site
Sparta, NJ, United States, 07871
Status
Recruitment Complete
Location
GSK Investigational Site
Iowa City, IA, United States, 52242
Status
Recruitment Complete
Location
GSK Investigational Site
Buenos Aires, Argentina, C1061AAS
Status
Recruitment Complete
Location
GSK Investigational Site
San Miguel de TucumAn, Argentina, T4000IHE
Status
Recruitment Complete
Location
GSK Investigational Site
Raleigh, NC, United States, 37421
Status
Recruitment Complete
Location
GSK Investigational Site
Jupiter, FL, United States, 33458
Status
Recruitment Complete
Location
GSK Investigational Site
Lakewood Ranch, FL, United States, 34211
Status
Recruitment Complete
Location
GSK Investigational Site
Coral Gables, FL, United States, 33134
Status
Study Complete
Location
GSK Investigational Site
Huntington Park, CA, United States, 90255
Status
Study Complete
Location
GSK Investigational Site
San Antonio, TX, United States, 78215
Status
Recruitment Complete
Location
GSK Investigational Site
New York, NY, United States, 10075
Status
Recruitment Complete
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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