Dose Exploration Study of GSK4532990 in. Participants With NASH or Suspected NASH (SKYLINE)

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 or Suspected NASH

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 24-36 weeks.

Study Overview

• Status: Completed
• Conditions: Non-alcoholic Fatty Liver Disease
• Intervention / Treatment: Drug: GSK4532990

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • Chula Vista, California, United States, 91911
      • GSK Investigational Site
    • Montclair, California, United States, 91763
      • GSK Investigational Site
    • San Diego, California, United States, 91942
      • GSK Investigational Site
    • San Diego, California, United States, 91911
      • GSK Investigational Site
  • Florida
    • Brandon, Florida, United States, 33511
      • GSK Investigational Site
    • Miami, Florida, United States, 33173
      • GSK Investigational Site
    • Miami, Florida, United States, 33155
      • GSK Investigational Site
    • Miami Lakes, Florida, United States, 33014
      • GSK Investigational Site
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • GSK Investigational Site
  • Kansas
    • El Dorado, Kansas, United States, 67042
      • GSK Investigational Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • GSK Investigational Site
  • Texas
    • Austin, Texas, United States, 78745
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78215
      • GSK Investigational Site
    • San Antonio, Texas, United States, 78240
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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®.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: GSK4532990 Dose 1; Participants will receive GSK4532990 Dose 1	Drug: GSK4532990; GSK4532990 will be administered
Experimental: GSK4532990 Dose 2; Participants will receive GSK4532990 Dose 2	Drug: GSK4532990; GSK4532990 will be administered
Experimental: GSK4532990 Dose 3; Participants will receive GSK4532990 Dose 3	Drug: GSK4532990; GSK4532990 will be administered
Experimental: GSK4532990 Dose 4; Participants will receive GSK4532990 Dose 4	Drug: GSK4532990; GSK4532990 will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Predicted percent change from baseline in liver biopsy-derived HSD17B13 protein expression levels	Baseline (Day 1) and up to Week 28
Predicted percent change from baseline in liver biopsy-derived HSD17B13 mRNA expression levels	Baseline (Day 1) and up to Week 28

Secondary Outcome Measures

Outcome Measure	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 28 post-dose
Percent change from baseline in the. observed HSD17B13 mRNA expression. levels	Baseline and Weeks 8, 12, or 28 post-dose

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2024
• Primary Completion (Actual): September 23, 2025
• Study Completion (Actual): September 23, 2025

Study Registration Dates

• First Submitted: October 23, 2023
• First Submitted That Met QC Criteria: October 23, 2023
• First Posted (Actual): October 27, 2023

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: October 13, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Keywords: Non-alcoholic fatty liver disease (NAFLD); GSK4532990; Non-alcoholic steatohepatitis (NASH); Suspected NASH
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver; Non-alcoholic Fatty Liver Disease
• Other Study ID Numbers: 218675

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Qualified researchers may request access to anonymized individual patient-level data (IPD) and related study documents of the eligible studies via the Data Sharing Portal. Details on GSK's data sharing criteria can be found at: https://www.gsk.com/en-gb/innovation/trials/data-transparency/
• IPD Sharing Time Frame: Anonymized IPD will be made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
• IPD Sharing Access Criteria: Anonymized IPD is shared with researchers whose proposals are approved by an Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension may be granted, when justified, for up to 6 months.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No