GSK4532990 for Fatty Liver Disease

(SKYLINE Trial)

Recruiting at 12 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Disqualifiers: Cirrhosis, Unstable liver disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

56 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a drug called GSK4532990 to understand its movement through the body and its effects on the liver in individuals with fatty liver disease. Researchers aim to ensure the drug's safety and effectiveness. The trial includes different groups receiving various doses to determine the optimal one. Individuals with a known or suspected diagnosis of NASH (a type of fatty liver disease) and stable medication use may be suitable candidates for this trial. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires participants to have stable use of their current medications, so you may not need to stop taking them. However, it's important to discuss your specific medications with the study team to ensure they meet the study's criteria.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that GSK4532990 has been tested in people before. In a study on liver disease related to alcohol, researchers focused on the treatment's safety, aiming to find the right dose and observe participants' reactions to the drug.

Previous studies have examined how GSK4532990 works in the liver and how the body processes it. These studies are crucial for ensuring the treatment's safety for further testing. Although specific safety details from these studies are not provided here, the progression of GSK4532990 to a Phase 2 trial suggests it demonstrated some level of safety. This stage of research typically indicates the treatment was generally well-tolerated in earlier tests.

For those considering joining a trial for GSK4532990, it is important to know that researchers closely monitored participants in earlier studies for any side effects. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Unlike the standard treatments for fatty liver disease, which often focus on lifestyle changes and medications like vitamin E or pioglitazone, GSK4532990 is unique because it targets the disease at a molecular level. Researchers are excited about GSK4532990 because it offers a novel approach by potentially modulating pathways directly involved in liver fat metabolism. This targeted action could lead to more effective management of the disease, potentially improving liver health and reducing the risk of progression to more severe liver conditions.

What evidence suggests that this trial's treatments could be effective for fatty liver disease?

Research has shown that GSK4532990 might help treat fatty liver disease by targeting a protein called HSD17B13, which is linked to liver issues like scarring and inflammation. Studies have found that GSK4532990 can lower HSD17B13 levels, potentially reducing liver damage. Previous tests demonstrated its potential to improve liver health by reducing liver fat and scarring. These findings suggest that GSK4532990 could be a promising treatment for fatty liver disease. Participants in this trial will receive one of several different doses of GSK4532990 to further evaluate its effectiveness and safety. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for adults aged 18 to 75 who have been diagnosed with NASH (a type of fatty liver disease) or are suspected to have it. They must be able to consent to the study and follow its rules, including stable use of any other medications they're on.

Inclusion Criteria

I have been diagnosed with or suspected to have NASH.

I can sign and follow the study's rules.

I have been on stable doses of my current medications.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of GSK4532990 to assess pharmacokinetics and pharmacodynamics

1 day

Follow-up

Participants are monitored for safety and effectiveness after treatment

22-34 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GSK4532990

Trial Overview The study is testing GSK4532990's effects in the body and liver, specifically looking at how it's processed and how it works against NASH. Participants will be involved in the study for about 24 weeks.

How Is the Trial Designed?

Group I: GSK4532990 Dose 4 Experimental Treatment 1 Intervention

Participants will receive GSK4532990 Dose 4

Group II: GSK4532990 Dose 3 Experimental Treatment 1 Intervention

Participants will receive GSK4532990 Dose 3

Group III: GSK4532990 Dose 2 Experimental Treatment 1 Intervention

Participants will receive GSK4532990 Dose 2

Group IV: GSK4532990 Dose 1 Experimental Treatment 1 Intervention

Participants will receive GSK4532990 Dose 1

Who Is Running the Clinical Trial?

GlaxoSmithKline

Lead Sponsor

Trials

4,834

Recruited

8,389,000+

Headquarters

London, UK

Known For

Vaccines & Medicines

Top Products

**Advair (salmeterol, fluticasone propionate)**, **Shingrix (shingles vaccine)**, **Augmentin (amoxicillin/clavulanate potassium)**, **Ventolin (salbutamol sulfate)

Dame Emma Walmsley

GlaxoSmithKline

Chief Executive Officer since 2017

MA in Classics and Modern Languages from Oxford University

Dr. Hal Barron

GlaxoSmithKline

Chief Medical Officer since 2018

MD from Harvard Medical School

Published Research Related to This Trial

In a study of 50 patients with biopsy-proven non-alcoholic fatty liver disease (NAFLD), common clinical features included fatigue (100%), hypertriglyceridemia (80%), and hepatomegaly (72%), indicating a clear pattern of symptoms associated with the disease.

Histopathological analysis revealed that 62% of patients had simple fatty liver, while 38% had nonalcoholic steatohepatitis (NASH), with a significant relationship found between hypertriglyceridemia and the presence of NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A clinical and biochemical profile of biopsy-proven non-alcoholic Fatty liver disease subjects. Khurram, M., Ashraf, MM.[2022]

Nonobese individuals account for approximately 29.7% of all NAFLD cases in the U.S., with a higher prevalence among older adults, males, and foreign-born Asians, indicating that NAFLD is not solely a condition associated with obesity.

Nonobese NAFLD has a significantly higher 15-year cumulative all-cause mortality rate (51.7%) compared to obese NAFLD (27.2%) and non-NAFLD individuals (20.7%), highlighting the need for targeted screening in high-risk populations regardless of obesity status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016. Zou, B., Yeo, YH., Nguyen, VH., et al.[2021]

Non-alcoholic fatty liver disease (NAFLD) is linked to increased cardiovascular risk due to its association with metabolic issues like glucose and lipoprotein metabolism.

Identifying NAFLD in patients should prompt a thorough evaluation of their cardiovascular risk, highlighting the need for integrated management strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non alcoholic fatty liver disease: a new risk factor for cardiovascular disease?]. Sdiri, W., Romdhane, H., Mbarek, D., et al.[2018]

The prevalence of nonalcoholic fatty liver disease (NAFLD) in the US is significant, affecting approximately 19% of adults, which translates to an estimated 28.8 million people, based on ultrasonography data from 12,454 participants in a national health survey.

NAFLD is more common among Mexican Americans (24.1%) and men (20.2%), and it is strongly associated with diabetes, insulin resistance, dyslipidemia, and obesity, indicating that these groups are at higher risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prevalence of nonalcoholic fatty liver disease in the United States: the Third National Health and Nutrition Examination Survey, 1988-1994. Lazo, M., Hernaez, R., Eberhardt, MS., et al.[2022]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the U.S., often linked to obesity, diabetes, and high cholesterol, and can progress to more severe liver conditions like cirrhosis.

Currently, there are no proven therapies for NAFLD, but experts recommend lifestyle changes such as exercise, weight loss, and managing blood sugar and cholesterol levels as key strategies for treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nonalcoholic steatohepatitis and the cardiometabolic syndrome. Abdeen, MB., Chowdhury, NA., Hayden, MR., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05583344

Phase 2b Study of GSK4532990 in Adults With NASH The purpose of this study is to measure improvements in liver fibrosis and inflammation with GSK4532990 compared with placebo in participants with NASH and ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT06104319

NCT06104319 | Dose Exploration Study of GSK4532990 in ... 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 ...

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36513186/

A phase I/II study of ARO-HSD, an RNA interference ... This proof-of-concept study demonstrated that short-term treatment with ARO-HSD reduces hepatic HSD17β13 mRNA and protein expression.

4. trial.medpath.com trial.medpath.com/clinical-trial/305c6278399c96d9/nct05583344-17-beta-hydroxysteroid-dehydrogenase-type-13-minimization-nash-treatment

Phase 2b Study of GSK4532990 in Adults With NASH | MedPath The purpose of this study is to measure improvements in liver fibrosis and inflammation with GSK4532990 compared with placebo in participants with NASH and ...

5. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/222291

GSK4532990 for Steatohepatitis in Adults With Alcohol-related ... This study aims to determine whether the study drug, GSK4532990, can improve ALD and reduce liver fatness by reducing the levels of HSD17B13 protein in the ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT06613698

NCT06613698 | A Study to Investigate the Safety and ... The goal of this study is to assess the safety and efficacy of GSK4532990 in participants with alcohol-related liver disease. Official Title. A Dose-Finding, ...

7. withpower.com withpower.com/trial/phase-2-liver-diseases-2024-2d91e

GSK4532990 for Fatty Liver Disease (SKYLINE Trial) 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 ...