Non-Alcoholic Steatohepatitis
Conditions
Interventions
- High Dose GSK4532990
- Low Dose GSK4532990
- Placebo
Sponsors
Okamasa Arisa
Eligibility
Sex/Gender
All
Inclusion 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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary objective will be achieved if one(or both) of the following dual endpoints are met in participants with NASH and bridging(F3) fibrosis: - Achieving >- 1 stage improvement in histological fibrosis (Clinical Research Network [CRN] scoring) with no worsening of NASH (defined as no increase in the NAFLD Activity Score [NAS] for steatosis, ballooning, or inflammation) at 52 weeks*1. -Achieving NASH resolution with no worsening of fibrosis (defined as no increase in CRN fibrosis score) at 52 weeks*1. Resolution of NASH is defined as a ballooning score of 0 and an inflammation score of 0-1. *1 In the absence of discontinuing study intervention prior to 24 weeks. | — |
Secondary
| Measure | Time frame |
|---|---|
| - Percentage of Participants Achieving >- 1 Stage Improvement in Histological Fibrosis with no Worsening of NASH - Pooled Cohort (F3 participants and F4 participants) at 52 weeks*1. - Percentage of Participants Achieving NASH Resolution with no Worsening of Fibrosis - Pooled Cohort (F3 participants and F4 participants)*1. - Change from baseline in Pro-C3 at 24 weeks and 52 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Change from baseline in liver fat using MRI-PDFF at 24 weeks and 52 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Change from baseline in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE_trademark) at 24 weeks and 52 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Change from baseline in Enhanced Liver Fibrosis (ELF_trademark) Score and its individual components (HA, PIIINP, TIMP-1) at 24 weeks and 52 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Achieving >=30% reduction from baseline in MRI-PDFF at 24 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Achieving >=30% reduction from baseline in MRI-PDFF at 52 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Change from baseline in ALT, AST and GGT at 24 weeks and 52 weeks - F3 Cohort and Pooled Cohort (F3 participants and F4 participants). - Occurrence of AEs and SAEs - F3 Cohort, F4 Cohort and Pooled Cohort (F3 participants and F4 participants). - Change from baseline in vital signs at each Visit - F3 Cohort, F4 Cohort and Pooled Cohort (F3 participants and F4 participants). - Change from baseline in key laboratory measurements at each Visit - F3 Cohort, F4 Cohort and Pooled Cohort (F3 participants and F4 participants). - In a subset of participants with intensive PK sampling: plasma PK parameters of GSK4532990 including area under the concentration-time curve from time zero (pre-dose) to t | — |
Countries
Argentina, Australia, Belgium, Canada, France, Greece, India, Italy, Japan, Korea, Mexico, Panama, Puerto Rico, Spain, Turkey, United Kingdom, United States
Contacts
Public ContactArisa Okamasa
GlaxoSmithKline K.K.
Outcome results
None listed