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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT06104319

Collaborator

(none)

Enrollment

Arms

16.5

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Non-alcoholic Fatty Liver Disease	Drug: GSK4532990	Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

48 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Jan 9, 2024

Anticipated Primary Completion Date :

May 26, 2025

Anticipated Study Completion Date :

May 26, 2025

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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®.