GSK4532990 for Fatty Liver Disease

(SKYLINE Trial)

Recruiting at12 trial locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: GlaxoSmithKline

Disqualifiers: Cirrhosis, Unstable liver disease, others

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this 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 (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.

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.

What makes the drug GSK4532990 unique for treating fatty liver disease?

There is no standard drug treatment for nonalcoholic fatty liver disease (NAFLD), making GSK4532990 a novel option. It is important to note that lifestyle changes like exercise and weight loss are currently emphasized for managing NAFLD. ^{1 2 3 4 5}

Research Team

Eligibility Criteria

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 am between 18 and 75 years old.

I can sign and follow the study's rules.

Trial Timeline

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

Treatment Details

Interventions

• GSK4532990 (Monoclonal Antibodies)

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.

Participant Groups

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

Findings from Research

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. England pubmed.ncbi.nlm.nih.gov

Prevalence, characteristics and mortality outcomes of obese, nonobese and lean NAFLD in the United States, 1999-2016. [2021]

3. Pakistan pubmed.ncbi.nlm.nih.gov

A clinical and biochemical profile of biopsy-proven non-alcoholic Fatty liver disease subjects. [2022]

4. Tunisia pubmed.ncbi.nlm.nih.gov

[Non alcoholic fatty liver disease: a new risk factor for cardiovascular disease?]. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Nonalcoholic steatohepatitis and the cardiometabolic syndrome. [2019]