Phase 2b Study of GSK4532990 in Adults with NASH

JRCT ID: jRCT2041220100

Registered date:28/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Non-Alcoholic Steatohepatitis
• Date of first enrollment: 10/01/2023
• Target sample size: 246
• Countries of recruitment: United States,Japan
• Study type: Interventional

Intervention(s)

- High Dose GSK4532990
- Low Dose GSK4532990
- Placebo

Outcome(s)

Primary Outcome

The primary objective will be achieved if one(or both) of the following dual endpoints are met:
- 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 weeks1. 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 Outcome

- Change from baseline in Pro-C3 at 24 weeks and 52 weeks.
- Change from baseline in liver fat using MRI-PDFF at 24 weeks and 52 weeks.
- Change from baseline in liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE trademark) at 24 weeks and 52 weeks.
- Change from baseline in Enhanced Liver Fibrosis (ELF trademark) Score and its individual components (HA, PIIINP, TIMP-1) at 24 weeks and 52 weeks.
- Achieving >=30% reduction from baseline in MRI-PDFF at 24 weeks.
- Achieving >=30% reduction from baseline in MRI-PDFF at 52 weeks.
- Change from baseline in ALT, AST and GGT at 24 weeks and 52 weeks.
- Occurrence of AEs and SAEs.
- Change from baseline in vital signs at each Visit.
- Change from baseline in key laboratory measurements at each Visit.
- 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 the last quantifiable concentration (AUC0-t), maximum observed concentration (Cmax), time of occurrence of Cmax (tmax), apparent terminal phase half-life (t1/2), apparent clearance (CL/F), and apparent terminal phase volume of distribution (Vz/F).
- Occurrence of anti-drug antibodies (ADA) to GSK4532990.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 75age old
• Gender: Both

Include criteria

- Body Mass Index (BMI) >-25 kilogram per meter square (kg/m2) (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.
- A liver biopsy at baseline showing NAFLD Activity Score (NAS) >-4 with at least 1 point each in steatosis, inflammation and ballooning and Fibrosis CRN score of 3.
- Able and willing to comply with all study assessments, including a liver biopsy at Week 52.

Exclude criteria

- Cirrhosis (based on screening biopsy or historical biopsy showing definitive cirrhosis).
- Current alcohol consumption >-14 standard drinks (24 units, 196 g ethanol) per week for females or >-21 standard drinks (37 units, 294 g ethanol) per week for males.
- Weight reduction surgery (including gastric banding and intragastric balloon insertion) within 2 years of Screening 1.
- History of cancer within previous 2 years from Screening 1, except adequately resected non-melanoma skin cancer.

Related Information

• Primary Sponsor: Okawa Yasutoshi
• Secondary ID(s): NCT05583344