Phase 2b Study of GSK4532990 in Adults With NASH

Nonalcoholic Fatty Liver Disease Clinical Trial

— HORIZON  

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05583344
• Other study ID #: 218672
• Secondary ID: 2022-002538-1420
• Status: Recruiting
• Phase: Phase 2
• Start date: January 2, 2023
• Est. completion date: December 15, 2025

Study information

• Verified date: March 2024
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 246
• Est. completion date: December 15, 2025
• Est. primary completion date: September 8, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Fatty Liver
• Liver Diseases
• Non-alcoholic Fatty Liver Disease
• Nonalcoholic Fatty Liver Disease

Intervention

Drug:
• GSK4532990
GSK4532990 will be administered.
• Placebo
Placebo will be administered.

Locations

Country	Name	City	State
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Buenos Aires
Argentina	GSK Investigational Site	Caba	Buenos Aires
Argentina	GSK Investigational Site	Ciudad Autonoma de Buenos Aires	Buenos Aires
Argentina	GSK Investigational Site	Derqui, Pilar	Buenos Aires
Argentina	GSK Investigational Site	San Miguel de Tucumán	Tucumán
Argentina	GSK Investigational Site	Santa Fe
Australia	GSK Investigational Site	Campbelltown	New South Wales
Australia	GSK Investigational Site	Nedlands	Western Australia
Australia	GSK Investigational Site	Perth	Western Australia
Belgium	GSK Investigational Site	Brussels
Belgium	GSK Investigational Site	Bruxelles
Belgium	GSK Investigational Site	Edegem
Canada	GSK Investigational Site	Calgary	Alberta
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Angers Cedex 9
France	GSK Investigational Site	Limoges cedex
France	GSK Investigational Site	Paris Cedex 13
France	GSK Investigational Site	Pessac cedex
France	GSK Investigational Site	Pierre-Bénite
France	GSK Investigational Site	Strasbourg Cedex
Greece	GSK Investigational Site	Athens
Greece	GSK Investigational Site	Rio
Greece	GSK Investigational Site	Thessaloniki
Greece	GSK Investigational Site	Thessaloniki
India	GSK Investigational Site	Bhubaneshwar, Odisha
India	GSK Investigational Site	Chandigarh
India	GSK Investigational Site	Chandigarh	Punjab
India	GSK Investigational Site	Coimbatore	Tamil Nadu
India	GSK Investigational Site	Guhawati	Assam
India	GSK Investigational Site	Mumbai	Maharashtra
India	GSK Investigational Site	Nagpur
India	GSK Investigational Site	New Delhi
India	GSK Investigational Site	Secunderabad
India	GSK Investigational Site	Surat	Gujarat
Italy	GSK Investigational Site	Baggiovara (MO)	Emilia-Romagna
Italy	GSK Investigational Site	Firenze	Toscana
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Padova	Veneto
Italy	GSK Investigational Site	Palermo	Sicilia
Italy	GSK Investigational Site	Roma	Lazio
Italy	GSK Investigational Site	Rozzano (MI)	Lombardia
Italy	GSK Investigational Site	San Giovanni Rotondo	Puglia
Japan	GSK Investigational Site	Fukui
Japan	GSK Investigational Site	Fukuoka
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Gifu
Japan	GSK Investigational Site	Hiroshima
Japan	GSK Investigational Site	Iwate
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagawa
Japan	GSK Investigational Site	Kagoshima
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kanagawa
Japan	GSK Investigational Site	Kyoto
Japan	GSK Investigational Site	Nagano
Japan	GSK Investigational Site	Nagasaki
Japan	GSK Investigational Site	Nara
Japan	GSK Investigational Site	Okayama
Japan	GSK Investigational Site	Osaka
Japan	GSK Investigational Site	Saga
Japan	GSK Investigational Site	Shimane
Japan	GSK Investigational Site	Yamanashi
Korea, Republic of	GSK Investigational Site	Incheon
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Korea, Republic of	GSK Investigational Site	Seoul
Mexico	GSK Investigational Site	Aguascalientes
Mexico	GSK Investigational Site	Cuernavaca	Morelos
Mexico	GSK Investigational Site	Guadalajara	Jalisco
Mexico	GSK Investigational Site	Merida
Panama	GSK Investigational Site	Ciudad de Panama
Panama	GSK Investigational Site	Panama
Puerto Rico	GSK Investigational Site	San Juan
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Majadahonda (Madrid)
Spain	GSK Investigational Site	Málaga
Spain	GSK Investigational Site	Pontevedra
Spain	GSK Investigational Site	Sabadell (Barcelona)
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Sevilla
Turkey	GSK Investigational Site	Ankara
Turkey	GSK Investigational Site	Gaziantep
Turkey	GSK Investigational Site	Izmir
Turkey	GSK Investigational Site	Kocaeli
Turkey	GSK Investigational Site	Rize
United Kingdom	GSK Investigational Site	Barnsley
United Kingdom	GSK Investigational Site	Cannock	Staffordshire
United Kingdom	GSK Investigational Site	Liverpool
United Kingdom	GSK Investigational Site	London
United Kingdom	GSK Investigational Site	Manchester
United Kingdom	GSK Investigational Site	Newcastle Upon Tyne
United Kingdom	GSK Investigational Site	Nottingham
United States	GSK Investigational Site	Akron	Ohio
United States	GSK Investigational Site	Ann Arbor	Michigan
United States	GSK Investigational Site	Athens	Georgia
United States	GSK Investigational Site	Austin	Texas
United States	GSK Investigational Site	Bastrop	Louisiana
United States	GSK Investigational Site	Bradenton	Florida
United States	GSK Investigational Site	Brownsville	Texas
United States	GSK Investigational Site	Chandler	Arizona
United States	GSK Investigational Site	Chapel Hill	North Carolina
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Chesterfield	Michigan
United States	GSK Investigational Site	Clarksville	Tennessee
United States	GSK Investigational Site	Colorado Springs	Colorado
United States	GSK Investigational Site	Columbia	Maryland
United States	GSK Investigational Site	Coral Gables	Florida
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Durham	North Carolina
United States	GSK Investigational Site	Edinburg	Texas
United States	GSK Investigational Site	Fort Myers	Florida
United States	GSK Investigational Site	Georgetown	Texas
United States	GSK Investigational Site	Greenbelt	Maryland
United States	GSK Investigational Site	Hallandale Beach	Florida
United States	GSK Investigational Site	Hialeah	Florida
United States	GSK Investigational Site	Hialeah Gardens	Florida
United States	GSK Investigational Site	Homestead	Florida
United States	GSK Investigational Site	Homewood	Alabama
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Houston	Texas
United States	GSK Investigational Site	Huntington Park	California
United States	GSK Investigational Site	Indianapolis	Indiana
United States	GSK Investigational Site	Iowa City	Iowa
United States	GSK Investigational Site	Jonesboro	Arkansas
United States	GSK Investigational Site	Jupiter	Florida
United States	GSK Investigational Site	La Jolla	California
United States	GSK Investigational Site	Lakewood Ranch	Florida
United States	GSK Investigational Site	Lancaster	Pennsylvania
United States	GSK Investigational Site	Las Vegas	Nevada
United States	GSK Investigational Site	Lawrence	New Jersey
United States	GSK Investigational Site	Marietta	Georgia
United States	GSK Investigational Site	Marrero	Louisiana
United States	GSK Investigational Site	Metairie	Louisiana
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami	Florida
United States	GSK Investigational Site	Miami Lakes	Florida
United States	GSK Investigational Site	Monroe	Louisiana
United States	GSK Investigational Site	Morehead City	North Carolina
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	New York	New York
United States	GSK Investigational Site	North Little Rock	Arkansas
United States	GSK Investigational Site	Orange	California
United States	GSK Investigational Site	Panorama City	California
United States	GSK Investigational Site	Peoria	Arizona
United States	GSK Investigational Site	Pittsburgh	Pennsylvania
United States	GSK Investigational Site	Poway	California
United States	GSK Investigational Site	Rialto	California
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Richmond	Virginia
United States	GSK Investigational Site	Sacramento	California
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Antonio	Texas
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Diego	California
United States	GSK Investigational Site	San Francisco	California
United States	GSK Investigational Site	Sandy Springs	Georgia
United States	GSK Investigational Site	Santa Ana	California
United States	GSK Investigational Site	Seattle	Washington
United States	GSK Investigational Site	Shreveport	Louisiana
United States	GSK Investigational Site	Snellville	Georgia
United States	GSK Investigational Site	South Bend	Indiana
United States	GSK Investigational Site	Southfield	Michigan
United States	GSK Investigational Site	Sparta	New Jersey
United States	GSK Investigational Site	Springboro	Ohio
United States	GSK Investigational Site	Topeka	Kansas
United States	GSK Investigational Site	Tucson	Arizona
United States	GSK Investigational Site	Waco	Texas
United States	GSK Investigational Site	West Jordan	Utah
United States	GSK Investigational Site	West Palm Beach	Florida
United States	GSK Investigational Site	Westlake	Ohio
United States	GSK Investigational Site	Wyomissing	Pennsylvania
United States	GSK Investigational Site	Ypsilanti	Michigan

Sponsors (1)

Lead Sponsor	Collaborator
GlaxoSmithKline

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Belgium,  Canada,  France,  Greece,  India,  Italy,  Japan,  Korea, Republic of,  Mexico,  Panama,  Puerto Rico,  Spain,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	At Week 52
Primary	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.	At Week 52
Secondary	Percentage of Participants Achieving = 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - Pooled Cohort (F3 participants and F4 participants)	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.	At Week 52
Secondary	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.	At Week 52
Secondary	Change from baseline in Pro-peptide of type III collagen (Pro-C3) - F3 Cohort		Baseline (Day 1) and at Week 24 and 52
Secondary	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
Secondary	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
Secondary	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.	Baseline (Day 1) and at Week 24 and 52
Secondary	Percentage of Participants Achieving =30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24- F3 Cohort		At Week 24
Secondary	Percentage of Participants Achieving =30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort		At Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Change from baseline in Enhanced Liver Fibrosis (ELF) Score - Pooled Cohort (F3 participants and F4 participants)	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.	Baseline (Day 1) and at Week 24 and 52
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F3 Cohort		Up to Week 66
Secondary	Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F3 Cohort		Baseline (Day 1) and up to Week 52
Secondary	Change from Baseline in Vital Signs - Temperature (Celsius) - F3 Cohort		Baseline (Day 1) and up to Week 52
Secondary	Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F3 Cohort		Baseline (Day 1) and up to Week 52
Secondary	Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F3 Cohort		Baseline (Day 1) and up to Week 52
Secondary	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
Secondary	Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F4 Cohort		Up to Week 66
Secondary	Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F4 Cohort		Baseline (Day 1) and up to Week 52
Secondary	Change from Baseline in Vital Signs - Temperature (Celsius) - F4 Cohort		Baseline (Day 1) and up to Week 52
Secondary	Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F4 Cohort		Baseline (Day 1) and up to Week 52
Secondary	Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F4 Cohort		Baseline (Day 1) and up to Week 52
Secondary	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
Secondary	Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - Pooled Cohort (F3 participants and F4 participants)		Up to Week 66
Secondary	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
Secondary	Change from Baseline in Vital Signs - Temperature (Celsius) - Pooled Cohort (F3 participants and F4 participants)		Baseline (Day 1) and up to Week 52
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F3 Cohort		Up to Week 52
Secondary	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
Secondary	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
Secondary	Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F4 Cohort		Up to Week 52