GSK4532990 for NASH

(HORIZON Trial)

Not currently recruiting at 185 trial locations

Overseen By US GSK Clinical Trials Call Center

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: GlaxoSmithKline

Disqualifiers: Alcohol use, Weight reduction surgery, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called GSK4532990 (also known as ARO-HSD or VSA-006) to determine if it can improve liver fibrosis and inflammation in people with NASH, a liver condition often linked to obesity and metabolic issues. Participants will receive either a high dose, low dose, or a placebo for up to a year. The trial seeks individuals who have had a liver biopsy showing advanced fibrosis and signs of metabolic syndrome, such as type 2 diabetes or high blood pressure. The goal is to determine if GSK4532990 can enhance liver health over time. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering a chance to contribute to significant advancements in liver health.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. Please consult with the study team for guidance.

Is there any evidence suggesting that GSK4532990 is likely to be safe for humans?

Research has shown that GSK4532990 is being tested for safety in treating non-alcoholic steatohepatitis (NASH). Although detailed safety data remains limited, the drug is currently in Phase 2 of testing. This phase follows initial tests in smaller groups to assess safety and side effects, and now researchers are evaluating its effectiveness in a larger group.

Specific information about side effects for GSK4532990 is not yet available, but its progression to this phase indicates it was safe enough to continue after initial tests. Prospective participants should discuss any potential risks with the trial team, who can provide more detailed information based on the latest research findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Researchers are excited about GSK4532990 for NASH because it offers a new approach by targeting a specific enzyme involved in fat metabolism. Unlike current treatments, which primarily focus on lifestyle changes and medications to manage symptoms, GSK4532990 works directly on the underlying metabolic processes contributing to NASH. This treatment comes in two doses, high and low, allowing researchers to explore its effectiveness and safety across different levels of administration. The potential to directly impact the disease mechanism makes it a promising candidate in the fight against NASH.

What evidence suggests that GSK4532990 might be an effective treatment for NASH?

Research shows that GSK4532990 is designed to treat non-alcoholic steatohepatitis (NASH), a liver condition causing inflammation and scarring. Early studies suggest this treatment might help reduce liver fibrosis, the thickening and scarring of liver tissue. A preliminary study found that a similar treatment reduced certain harmful proteins in the liver. This suggests that GSK4532990 could potentially improve liver health by targeting the root causes of NASH. Although more research is needed, these early results offer hope that GSK4532990 might effectively treat advanced liver fibrosis in NASH patients. Participants in this trial will receive either a high dose or low dose of GSK4532990, or a placebo, to evaluate its effectiveness and safety. ^{1 2 3 5 6}

Who Is on the Research Team?

GSK Clinical Trials

Principal Investigator

GlaxoSmithKline

Are You a Good Fit for This Trial?

Adults with a liver condition called NASH and advanced fibrosis can join this trial. They must have a BMI of at least 25, or 23 for Asian participants, and show certain features on a liver biopsy. Participants need to be able to follow the study plan, including another biopsy after one year. People who've had weight reduction surgery recently, have cirrhosis, drink heavily, or had cancer (except some skin cancers) in the last two years cannot join.

Inclusion Criteria

My liver biopsy shows I have significant fatty liver disease with inflammation and scarring.

Able and willing to comply with all study assessments, including a liver biopsy at Week 52

Body Mass Index (BMI) ≥25 kg/m^2 (all ethnic origins) except for Asian participants who qualify for the study with BMI ≥23 kg/m^2 at Screening

Exclusion Criteria

Current alcohol consumption ≥14 standard drinks (24 units, 196 g ethanol) per week for females or ≥21 standard drinks (37 units, 294g ethanol) per week for males

I have been diagnosed with cirrhosis through a biopsy.

I have not had weight loss surgery in the last 2 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

up to 24 weeks

Treatment

Participants receive GSK4532990 or placebo for the treatment of NASH

52 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• GSK4532990
• Placebo

Trial Overview The trial is testing GSK4532990 against a placebo to see if it's better at reducing liver scarring and inflammation in people with NASH. Everyone will be randomly assigned to either get GSK4532990 or a dummy pill (placebo), and they won't know which one they're taking for up to 52 weeks of treatment.

How Is the Trial Designed?

Group I: Low Dose GSK4532990 Experimental Treatment 1 Intervention

Group II: High Dose GSK4532990 Experimental Treatment 1 Intervention

Group III: Placebo Placebo Group 1 Intervention

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

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. arrowheadpharma.com arrowheadpharma.com/news-press/arrowhead-pharmaceuticals-announces-30-million-milestone-payment-from-gsk/

Arrowhead Pharmaceuticals Announces $30 Million ... The double-blind, placebo-controlled Phase 2b HORIZON trial (NCT05583344) will evaluate the efficacy and safety of GSK4532990 in adults with pre-cirrhotic NASH.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06104319

NCT06104319 | Dose Exploration Study of GSK4532990 in ... GSK4532990. Non-alcoholic steatohepatitis (NASH). Non-alcoholic fatty liver disease (NAFLD). Suspected NASH. Additional Relevant MeSH Terms. Fatty Liver. Liver ...

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-gsk4532990-for-adults-with-nonalcoholic-steatohepatitis-nash/

Study on GSK4532990 for Adults with Nonalcoholic ... The purpose of the study is to evaluate whether this treatment can help improve liver health by reducing liver fibrosis (scarring) and resolving NASH in adults ...

5. 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.

6. ir.arrowheadpharma.com ir.arrowheadpharma.com/news-releases/news-release-details/arrowhead-pharmaceuticals-announces-30-million-milestone-payment

Arrowhead Pharmaceuticals Announces $30 Million ... The double-blind, placebo-controlled Phase 2b HORIZON trial (NCT05583344) will evaluate the efficacy and safety of GSK4532990 in adults with pre ...