Clinical trial NCT05583344: Phase 2b Study of GSK4532990 in Adults With NASH
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
Conditions: Nonalcoholic Fatty Liver Disease
Non-alcoholic Fatty Liver Disease
Keywords: 17β-Hydroxysteroid Dehydrogenase type 13 Minimization for the treatment of NASH (HORIZON)
GSK4532990
Non-alcoholic steatohepatitis (NASH)
Non-alcoholic fatty liver disease (NAFLD)
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
First posted: 2022-10-17
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants Achieving ≥ 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - F3 Cohort
timeFrame: At Week 52
measure: Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - F3 Cohort
timeFrame: At Week 52
Secondary outcomes:
measure: 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
measure: Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - Pooled Cohort (F3 participants and F4 participants)
timeFrame: At Week 52
measure: Change from baseline in Pro-peptide of type III collagen (Pro-C3) - F3 Cohort
timeFrame: Baseline (Day 1) and at Week 24 and 52
measure: 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
measure: 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
measure: Change from baseline in Enhanced Liver Fibrosis (ELF) Score - F3 Cohort
timeFrame: Baseline (Day 1) and at Week 24 and 52
measure: Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 24- F3 Cohort
timeFrame: At Week 24
measure: Percentage of Participants Achieving ≥30% relative reduction in liver fat from baseline using MRI-PDFF at Week 52 - F3 Cohort
timeFrame: At Week 52
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F3 Cohort
timeFrame: Up to Week 66
measure: Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F3 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: Change from Baseline in Vital Signs - Temperature (Celsius) - F3 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F3 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F3 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: 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
measure: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - F4 Cohort
timeFrame: Up to Week 66
measure: Change from Baseline in Vital Signs - Blood Pressure (millimeters of Mercury) - F4 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: Change from Baseline in Vital Signs - Temperature (Celsius) - F4 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: Change from Baseline in Vital Signs - Heart Rate (Beats per minute) - F4 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: Change from Baseline in Vital Signs - Respiratory Rate (Breaths per minute) - F4 Cohort
timeFrame: Baseline (Day 1) and up to Week 52
measure: 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
measure: Percentage of Participants with Adverse Events (AEs) and Serious Adverse Events (SAEs) - Pooled Cohort (F3 participants and F4 participants)
timeFrame: Up to Week 66
measure: 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
measure: Change from Baseline in Vital Signs - Temperature (Celsius) - Pooled Cohort (F3 participants and F4 participants)
timeFrame: Baseline (Day 1) and up to Week 52
measure: 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
measure: 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
measure: 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
measure: 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
measure: 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
measure: Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F3 Cohort
timeFrame: Up to Week 52
measure: 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
measure: 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
measure: Percentage of Participants with Anti-drug Antibodies (ADA) to GSK4532990- F4 Cohort
timeFrame: Up to Week 52
Other outcomes:
Locations:
city: Homewood
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facility: GSK Investigational Site
state: Alabama
city: Chandler
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facility: GSK Investigational Site
state: Arizona
city: Chandler
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facility: GSK Investigational Site
state: Arizona
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city: Jonesboro
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state: Arkansas
city: North Little Rock
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state: Arkansas
city: Huntington Park
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facility: GSK Investigational Site
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city: La Jolla
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facility: GSK Investigational Site
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city: Orange
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facility: GSK Investigational Site
state: California
city: Poway
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facility: GSK Investigational Site
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facility: GSK Investigational Site
state: California
city: Sacramento
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state: California
city: San Francisco
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state: California
city: Colorado Springs
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facility: GSK Investigational Site
state: Colorado
city: Bradenton
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state: Florida
city: Coral Gables
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facility: GSK Investigational Site
state: Florida
city: Fort Myers
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facility: GSK Investigational Site
state: Florida
city: Hallandale Beach
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facility: GSK Investigational Site
state: Florida
city: Hialeah
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city: Homestead
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state: Florida
city: Jupiter
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facility: GSK Investigational Site
state: Florida
city: Lakewood Ranch
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facility: GSK Investigational Site
state: Florida
city: Miami Lakes
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facility: GSK Investigational Site
state: Florida
city: Miami
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facility: GSK Investigational Site
state: Florida
city: Miami
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facility: GSK Investigational Site
state: Florida
city: Miami
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facility: GSK Investigational Site
state: Florida
city: West Palm Beach
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facility: GSK Investigational Site
state: Florida
city: Athens
country: United States
facility: GSK Investigational Site
state: Georgia
city: Marietta
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facility: GSK Investigational Site
state: Georgia
city: Sandy Springs
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facility: GSK Investigational Site
state: Georgia
city: Snellville
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facility: GSK Investigational Site
state: Georgia
city: Indianapolis
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facility: GSK Investigational Site
state: Indiana
city: South Bend
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facility: GSK Investigational Site
state: Indiana
city: Iowa City
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facility: GSK Investigational Site
state: Iowa
city: Topeka
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state: Kansas
city: Marrero
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facility: GSK Investigational Site
state: Louisiana
city: Marrero
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facility: GSK Investigational Site
state: Louisiana
city: Monroe
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state: Louisiana
city: Monroe
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state: Louisiana
city: Shreveport
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state: Louisiana
city: Columbia
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state: Maryland
city: Greenbelt
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city: Ann Arbor
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city: Southfield
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city: Ypsilanti
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city: Princeton
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facility: GSK Investigational Site
state: New Jersey
city: Sparta
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facility: GSK Investigational Site
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city: New York
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facility: GSK Investigational Site
state: New York
city: New York
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facility: GSK Investigational Site
state: New York
city: New York
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facility: GSK Investigational Site
state: New York
city: Chapel Hill
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facility: GSK Investigational Site
state: North Carolina
city: Durham
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Morehead City
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Raleigh
country: United States
facility: GSK Investigational Site
state: North Carolina
city: Akron
country: United States
facility: GSK Investigational Site
state: Ohio
city: Springboro
country: United States
facility: GSK Investigational Site
state: Ohio
city: Westlake
country: United States
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state: Ohio
city: Lancaster
country: United States
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state: Pennsylvania
city: Pittsburgh
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facility: GSK Investigational Site
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city: Wyomissing
country: United States
facility: GSK Investigational Site
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city: Clarksville
country: United States
facility: GSK Investigational Site
state: Tennessee
city: Austin
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state: Texas
city: Brownsville
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facility: GSK Investigational Site
state: Texas
city: Dallas
country: United States
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state: Texas
city: Edinburg
country: United States
facility: GSK Investigational Site
state: Texas
city: Georgetown
country: United States
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state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: Houston
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: San Antonio
country: United States
facility: GSK Investigational Site
state: Texas
city: Waco
country: United States
facility: GSK Investigational Site
state: Texas
city: West Jordan
country: United States
facility: GSK Investigational Site
state: Utah
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Richmond
country: United States
facility: GSK Investigational Site
state: Virginia
city: Seattle
country: United States
facility: GSK Investigational Site
state: Washington
city: Buenos Aires
country: Argentina
facility: GSK Investigational Site
city: Capital Federal
country: Argentina
facility: GSK Investigational Site
city: Ciudad AutOnoma de Buenos Aire
country: Argentina
facility: GSK Investigational Site
city: Ciudad Autonoma De Bueno
country: Argentina
facility: GSK Investigational Site
city: Pilar
country: Argentina
facility: GSK Investigational Site
city: Rosario
country: Argentina
facility: GSK Investigational Site
city: San Miguel de TucumAn
country: Argentina
facility: GSK Investigational Site
city: Nedlands
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Perth
country: Australia
facility: GSK Investigational Site
state: Western Australia
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Bruxelles
country: Belgium
facility: GSK Investigational Site
city: Edegem
country: Belgium
facility: GSK Investigational Site
city: Calgary
country: Canada
facility: GSK Investigational Site
state: Alberta
city: Toronto
country: Canada
facility: GSK Investigational Site
state: Ontario
city: Angers Cedex 9
country: France
facility: GSK Investigational Site
city: Limoges Cedex
country: France
facility: GSK Investigational Site
city: Paris
country: France
facility: GSK Investigational Site
city: Pierre Benite
country: France
facility: GSK Investigational Site
city: Strasbourg
country: France
facility: GSK Investigational Site
city: Athens
country: Greece
facility: GSK Investigational Site
city: Rio Patras
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Thessaloniki
country: Greece
facility: GSK Investigational Site
city: Bhubaneswar
country: India
facility: GSK Investigational Site
city: Chandigarh
country: India
facility: GSK Investigational Site
city: Coimbatore
country: India
facility: GSK Investigational Site
city: Guwahati
country: India
facility: GSK Investigational Site
city: Mumbai
country: India
facility: GSK Investigational Site
city: Nagpur
country: India
facility: GSK Investigational Site
city: New Delhi
country: India
facility: GSK Investigational Site
city: Secunderabad
country: India
facility: GSK Investigational Site
city: Surat
country: India
facility: GSK Investigational Site
city: Firenze
country: Italy
facility: GSK Investigational Site
city: Milano
country: Italy
facility: GSK Investigational Site
city: Modena
country: Italy
facility: GSK Investigational Site
city: Padova
country: Italy
facility: GSK Investigational Site
city: Palermo
country: Italy
facility: GSK Investigational Site
city: Roma
country: Italy
facility: GSK Investigational Site
city: Rozzano MI
country: Italy
facility: GSK Investigational Site
city: San Giovanni Rotondo FG
country: Italy
facility: GSK Investigational Site
city: Fukui
country: Japan
facility: GSK Investigational Site
city: Fukuoka
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Gifu
country: Japan
facility: GSK Investigational Site
city: Hiroshima
country: Japan
facility: GSK Investigational Site
city: Iwate
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagawa
country: Japan
facility: GSK Investigational Site
city: Kagoshima
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Kanagawa
country: Japan
facility: GSK Investigational Site
city: Nagano
country: Japan
facility: GSK Investigational Site
city: Nagasaki
country: Japan
facility: GSK Investigational Site
city: Nara
country: Japan
facility: GSK Investigational Site
city: Okayama
country: Japan
facility: GSK Investigational Site
city: Osaka
country: Japan
facility: GSK Investigational Site
city: Saga
country: Japan
facility: GSK Investigational Site
city: Shimane
country: Japan
facility: GSK Investigational Site
city: Yamanashi
country: Japan
facility: GSK Investigational Site
city: Incheon
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Yongsan-Ku Seoul
country: Korea, Republic of
facility: GSK Investigational Site
city: Cuernavaca Morelos
country: Mexico
facility: GSK Investigational Site
city: Guadalajara
country: Mexico
facility: GSK Investigational Site
city: Merida
country: Mexico
facility: GSK Investigational Site
city: Panama City
country: Panama
facility: GSK Investigational Site
city: Panama
country: Panama
facility: GSK Investigational Site
city: San Juan
country: Puerto Rico
facility: GSK Investigational Site
city: Barcelona
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Madrid
country: Spain
facility: GSK Investigational Site
city: Malaga
country: Spain
facility: GSK Investigational Site
city: Sabadell Barcelona
country: Spain
facility: GSK Investigational Site
city: Santander
country: Spain
facility: GSK Investigational Site
city: Sevilla
country: Spain
facility: GSK Investigational Site
city: Vigo
country: Spain
facility: GSK Investigational Site
city: Ankara
country: Turkey
facility: GSK Investigational Site
city: Kocaeli
country: Turkey
facility: GSK Investigational Site
city: Rize
country: Turkey
facility: GSK Investigational Site
city: Cannock
country: United Kingdom
facility: GSK Investigational Site
city: London
country: United Kingdom
facility: GSK Investigational Site
city: Manchester
country: United Kingdom
facility: GSK Investigational Site
city: Newcastle Upon Tyne
country: United Kingdom
facility: GSK Investigational Site
city: Nottingham
country: United Kingdom
facility: GSK Investigational Site
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References: