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NCT Number: NCT05583344

Phase 2b Study of GSK4532990 in Adults With NASH

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.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Conditions

Nonalcoholic Fatty Liver Disease Digestive System Diseases Fatty Liver Liver Diseases Non-Alcoholic Fatty Liver Disease

Age range

18 year–75 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

GSK Investigational Site, Buenos Aires, Argentina

Loading trial locations.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

GSK4532990

Drug

GSK4532990 will be administered.

Placebo

Drug

Placebo will be administered.

Primary outcomes

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

    Time frame: 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.

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

    Time frame: 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 outcomes

  1. 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

    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.

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

    Time frame: 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.

  3. 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

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

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

  5. 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

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

    Time frame: 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.

  7. 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

  8. 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

  9. 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

  10. 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

  11. 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

  12. 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

  13. 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

    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.

  14. 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

  15. 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

  16. 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

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

    Time frame: Up to Week 66

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

    Time frame: Baseline (Day 1) and up to Week 52

  19. Change from Baseline in Vital Signs - Temperature (Celsius) - F3 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  20. Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F3 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  21. Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F3 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  22. Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F3 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  23. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F4 Cohort

    Time frame: Up to Week 66

  24. Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F4 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  25. Change from Baseline in Vital Signs - Temperature (Celsius) - F4 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  26. Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F4 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  27. Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F4 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  28. Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - F4 Cohort

    Time frame: Baseline (Day 1) and up to Week 52

  29. Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - Pooled Cohort (F3 participants and F4 participants)

    Time frame: Up to Week 66

  30. Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - Pooled Cohort (F3 participants and F4 participants)

    Time frame: Baseline (Day 1) and up to Week 52

  31. Change from Baseline in Vital Signs - Temperature (Celsius) - Pooled Cohort (F3 participants and F4 participants)

    Time frame: Baseline (Day 1) and up to Week 52

  32. Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - Pooled Cohort (F3 participants and F4 participants)

    Time frame: Baseline (Day 1) and up to Week 52

  33. Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - Pooled Cohort (F3 participants and F4 participants)

    Time frame: Baseline (Day 1) and up to Week 52

  34. Change From Baseline in Clinical Chemistry Parameter: total bilirubin, direct Bilirubin and creatinine (Micromoles per Liter) - Pooled Cohort (F3 participants and F4 participants)

    Time frame: Baseline (Day 1) and up to Week 52

  35. Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F3 Cohort

    Time frame: Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose

  36. Maximum observed concentration (Cmax) of GSK4532990- F3 Cohort

    Time frame: Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose

  37. Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F3 Cohort

    Time frame: Up to Week 52

  38. Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 - F4 Cohort

    Time frame: Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose

  39. Maximum observed concentration (Cmax) of GSK4532990- F4 Cohort

    Time frame: Pre-dose (Day 1), 0.25, 0.5, 1, 2, 4, 8, 12 and 24 hours post dose

  40. Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F4 Cohort

    Time frame: Up to Week 52

Sponsors and collaborators

Lead sponsor

GlaxoSmithKline

Industry

Registry information

Official study 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

Acronym: HORIZON

Important dates

Study start
2023
Primary completion
2026
Study completion
2026
First posted
Oct 17, 2022
Registry last updated
Jun 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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