Dose Exploration Study of GSK4532990 in Participants With NASH or Suspected NASH

Study Overview
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Brief Summary
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The purpose of this study is to understand how the drug GSK4532990 is processed in the body (pharmacokinetics) and how it works in the liver (pharmacodynamics) as well as to ensure it is safe and well-tolerated. The total study duration for each participant will be approximately 24 weeks.

Official Title
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A Phase 2a, Single Dose, Open-label, Dose Exploration Study to Assess the PK-PD Activity, Safety, and Tolerability of GSK4532990 in Adult. Participants With NASH and Suspected NASH

Conditions
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Non-alcoholic Fatty Liver Disease

Intervention / Treatment
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* Drug: GSK4532990


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must be 18 to 75 years of age. Participant must be capable of giving signed informed consent which includes compliance with the requirements and restrictions listed for the study. Participants who have proven diagnosis of NASH or suspected NASH based on defined study criteria. Participants must meet predefined stable use requirements of concomitant medications based on study criteria. Exclusion Criteria: Individuals who meet any of the following exclusion criteria will not be eligible to participate in the study: Cirrhosis or current unstable liver or biliary disease. Other causes of liver disease including, but not limited to, alcohol-related liver disease, autoimmune disorders. Known weight loss of ≥5% within 3 months prior to Screening. Weight reduction surgery or procedures within 2 years of Screening. Any contraindication to undergoing liver biopsy. Any contraindication to undergoing Magnetic Resonance Imaging or FibroScan®.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GSK4532990 Dose 1<br>Participants will receive GSK4532990 Dose 1 | Drug: GSK4532990<br>* GSK4532990 will be administered<br>|
| Experimental: GSK4532990 Dose 2<br>Participants will receive GSK4532990 Dose 2 | Drug: GSK4532990<br>* GSK4532990 will be administered<br>|
| Experimental: GSK4532990 Dose 3<br>Participants will receive GSK4532990 Dose 3 | Drug: GSK4532990<br>* GSK4532990 will be administered<br>|
| Experimental: GSK4532990 Dose 4<br>Participants will receive GSK4532990 Dose 4 | Drug: GSK4532990<br>* GSK4532990 will be administered<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predicted percent change from baseline in liver biopsy-derived HSD17B13 protein expression levels |  | Baseline (Day 1) and up to Week 16 | 
| Predicted percent change from baseline in liver biopsy-derived HSD17B13 mRNA expression levels |  | Baseline (Day 1) and up to Week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area under the concentration-time curve from time zero (pre-dose) to the last quantifiable concentration (AUC0-t) of GSK4532990 |  | Pre-dose (Day 1), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose | 
| Maximum observed concentration (Cmax) of GSK4532990 |  | Pre-dose (Day 1), 0.25, 0.5, 1, 2, 3, 4, 6, 8, 12, 24 and 48 hours post dose | 
| Percent change from baseline in the observed HSD17B13 protein expression levels |  | Baseline and Weeks 8, 12, or 16 post-dose | 
| Percent change from baseline in the observed HSD17B13 mRNA expression levels |  | Baseline and Weeks 8, 12, or 16 post-dose | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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GSK4532990, Non-alcoholic steatohepatitis (NASH), Non-alcoholic fatty liver disease (NAFLD), Suspected NASH