HM15211 for Non-alcoholic Steatohepatitis (NASH)

Not currently recruiting at 88 trial locations

Overseen By Eric Lawitz

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Hanmi Pharmaceutical Company Limited

Must not be taking: Corticosteroids, Methotrexate, Insulin, others

Disqualifiers: Chronic liver disease, Type 1 diabetes, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, HM15211 (also known as Efocipegtrutide, a GLP-1/GIP/glucagon triagonist), for individuals with non-alcoholic steatohepatitis (NASH), a liver condition that causes inflammation and damage due to fat buildup. The trial aims to determine the treatment's effectiveness, safety, and tolerability over 12 months. Participants will receive either the experimental treatment or a placebo (a substance with no active treatment) to compare outcomes. Suitable candidates for this trial have a confirmed diagnosis of non-cirrhotic NASH with liver fibrosis and stable body weight for at least three months. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I need to stop my current medications for the trial?

The trial does not specify if you need to stop your current medications, but it excludes those who have recently used certain drugs linked to liver issues or those with specific diabetes treatments. It's best to discuss your current medications with the trial team.

Is there any evidence suggesting that HM15211 is likely to be safe for humans?

Research has shown that HM15211 underwent safety testing in earlier trials. In some studies, it reduced liver fat and body weight in individuals with non-alcoholic fatty liver disease, related to NASH. These studies provided safety information by examining the body's response to the treatment.

Although these studies did not specifically target NASH, results suggest that HM15211 was generally well-tolerated, with no major safety issues reported. As a phase 2 study, the treatment has already passed initial safety checks in earlier phases. However, it is still under careful study to ensure safety for people with NASH.

It is important to remember that any treatment can have side effects, so discussing participation with a healthcare provider is advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

HM15211 is unique because it offers a fresh approach to treating Non-alcoholic Steatohepatitis (NASH) by targeting specific pathways in the liver that current treatments might not address as effectively. Current standard treatments for NASH often focus on managing symptoms or related conditions like diabetes and high cholesterol, but HM15211 aims to directly influence the biological mechanisms causing liver inflammation and fat accumulation. Researchers are excited about HM15211 because it represents a novel way to combat the progression of liver damage, potentially offering a more effective and targeted solution for patients suffering from this chronic liver disease.

What evidence suggests that HM15211 might be an effective treatment for NASH?

Research has shown that HM15211, which participants in this trial may receive, is a promising treatment for Non-alcoholic Steatohepatitis (NASH). This new medication targets three different hormones to reduce liver fat and scarring. Animal studies showed improvements in liver health, and early human trials indicated it helped lower liver fat and body weight. These results suggest HM15211 could be an effective option for treating NASH and related liver issues. ^{1 3 4 5 6}

Are You a Good Fit for This Trial?

Adults aged 18-70 with non-cirrhotic NASH and liver fibrosis stages F1-F3, confirmed by a biopsy within the last 6 months. Participants must have at least 8% liver fat on MRI-PDFF and a stable body weight for the past three months. Excluded are those with significant chronic liver diseases, recent use of certain NAFLD-related therapies, Type 1 diabetes or specific Type 2 diabetes treatments.

Inclusion Criteria

BMI ≥ 18 kg/m2, with stable body weight (defined as change < 5%) by history for 3 months prior to screening or since baseline liver biopsy, whichever is earlier.

MRI-PDFF performed at screening with ≥ 8% steatosis.

My liver condition is noncirrhotic NASH with fibrosis stage F1-F3, confirmed by a biopsy.

Exclusion Criteria

I have used medications recently that could cause fatty liver disease.

I have never had serious liver disease or been hospitalized for it.

I have a history of liver disease or HIV.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive HM15211 or placebo for 12 months to evaluate efficacy, safety, and tolerability in subjects with biopsy-confirmed NASH

12 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• HM15211
• Placebo of HM15211

Trial Overview The trial is testing HM15211's effectiveness over a year in treating NASH compared to a placebo. It's designed to see if this treatment can improve fatty liver disease without causing harm or discomfort to patients.

How Is the Trial Designed?

Group I: HM15211 Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Hanmi Pharmaceutical Company Limited

Lead Sponsor

Trials

196

Recruited

62,100+

Young Choi

Hanmi Pharmaceutical Company Limited

Chief Medical Officer since 2023

PhD in Pharmacology from Yonsei University

Jae-Hyun Park

Hanmi Pharmaceutical Company Limited

Chief Executive Officer since 2024

MD from Seoul National University

Published Research Related to This Trial

In a study using non-obese mice with nonalcoholic steatohepatitis (NASH), the GLP-1 analogue exendin-4 significantly reduced liver fat accumulation and inflammation after four weeks of treatment, indicating its potential efficacy in managing NASH.

Exendin-4 works by inhibiting the influx of free fatty acids into the liver and reducing oxidative stress, which helps to alleviate the symptoms of hepatic steatosis and inflammation associated with NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice. Yamamoto, T., Nakade, Y., Yamauchi, T., et al.[2022]

In preclinical models of NASH, the combination of the lysophosphatidic acid receptor 1 antagonist EPGN2154 and the glucagon-like peptide-1 agonist semaglutide (Sema) resulted in the greatest body weight loss compared to other treatment groups, indicating a potential synergistic effect.

EPGN2154 showed a protective effect on the liver, reducing the NAFLD Activity Score and the incidence of advanced hepatic fibrosis, independent of body weight loss, suggesting its efficacy in treating NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lysophosphatidic acid receptor 1 antagonist (EPGN2154) causes regression of NASH in preclinical NASH models. Bhattacharjee, J., Beaton, G., Ravula, SB., et al.[2023]

HM15211 (efocipegtrutide) is a promising new treatment for non-alcoholic steatohepatitis (NASH), showing efficacy in early studies and manageable toxicity, with a phase 2 trial involving 217 patients designed to assess its effectiveness over 52 weeks.

The innovative adaptive design of the study aims to reduce the need for invasive liver biopsies while ensuring that patients receive optimal doses of HM15211, allowing for a more efficient evaluation of its safety and efficacy in treating NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase 2, adaptive randomized, double-blind, placebo-controlled, multicenter, 52-week study of HM15211 in patients with biopsy-confirmed non-alcoholic steatohepatitis - Study design and rationale of HM-TRIA-201 study. Abdelmalek, MF., Suzuki, A., Sanchez, W., et al.[2023]

In a phase IIa study involving 145 participants with non-alcoholic fatty liver disease (NAFLD), efinopegdutide (10 mg weekly) resulted in a significantly greater reduction in liver fat content (LFC) compared to semaglutide (1 mg weekly), with reductions of 72.7% and 42.3% respectively after 24 weeks (p < 0.001).

Both treatments led to weight loss, with efinopegdutide showing an 8.5% reduction compared to 7.1% for semaglutide, although efinopegdutide was associated with slightly higher gastrointestinal adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A phase IIa active-comparator-controlled study to evaluate the efficacy and safety of efinopegdutide in patients with non-alcoholic fatty liver disease. Romero-Gómez, M., Lawitz, E., Shankar, RR., et al.[2023]

In a phase 2 trial involving 71 patients with NASH-related cirrhosis, semaglutide did not significantly improve liver fibrosis or lead to NASH resolution compared to placebo after 48 weeks.

The safety profile of semaglutide was similar to that of the placebo, with no new safety concerns identified, and common side effects included nausea and diarrhea, but overall liver and kidney function remained stable.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide 2·4 mg once weekly in patients with non-alcoholic steatohepatitis-related cirrhosis: a randomised, placebo-controlled phase 2 trial. Loomba, R., Abdelmalek, MF., Armstrong, MJ., et al.[2023]

GLP-1 receptor (GLP-1R) agonists, which are effective in treating type 2 diabetes and obesity, show promise as potential therapeutic agents for nonalcoholic steatohepatitis (NASH), a severe form of fatty liver disease.

The article discusses the complex pathogenesis of NASH and highlights the pharmacological effects of GLP-1 mimetics, including their mechanisms of action, suggesting they could be beneficial in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis. Chen, Y., Xu, YN., Ye, CY., et al.[2023]

SAR441255, a triagonist targeting GLP-1R, GIPR, and GcgR, demonstrated positive effects on glucose regulation in humans after single doses, indicating its potential for managing blood sugar levels.

The drug showed an acceptable safety profile, particularly regarding gastrointestinal tolerability and cardiovascular effects, suggesting it may be a safe option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

GLP-1/GIP/glucagon receptor triagonism gets its try in humans. Finan, B., Douros, JD.[2022]

In a study involving 14 patients with biopsy-proven non-alcoholic steatohepatitis (NASH), the GLP-1 analogue liraglutide significantly improved metabolic markers, reducing body mass index (BMI), HbA1c, and liver enzymes, indicating its efficacy in addressing metabolic dysfunction associated with NASH.

Liraglutide enhanced insulin sensitivity in both the liver and adipose tissue, decreased hepatic lipogenesis, and may serve as a potential disease-modifying treatment for NASH, highlighting its role in combating insulin resistance and lipotoxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. Armstrong, MJ., Hull, D., Guo, K., et al.[2022]

In a study involving C57BL/6J mice with diet-induced non-alcoholic steatohepatitis (NASH), combining GLP-1 receptor agonism with glucagon and GIP receptor agonism led to greater reductions in liver fat and improved liver health compared to using GLP-1 alone.

The dual GLP-1R/GCGR agonist and the combination of all three receptor agonists showed significantly better results in reducing liver disease activity compared to high-dose liraglutide, indicating that targeting multiple receptors can enhance treatment efficacy without relying solely on weight loss.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incretin combination therapy for the treatment of non-alcoholic steatohepatitis. Kannt, A., Madsen, AN., Kammermeier, C., et al.[2021]

Citations

1. sciencedirect.com sciencedirect.com/science/article/abs/pii/S155171442300099X

A phase 2, adaptive randomized, double-blind, placebo ... The adaptive design study of HM15211 minimizes the number of patients to be exposed to a liver biopsy while optimizing the sample size of patients exposed to ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37028504/

Study design and rationale of HM-TRIA-201 study The adaptive design study of HM15211 minimizes the number of patients to be exposed to a liver biopsy while optimizing the sample size of patients exposed to ...

3. diabetesjournals.org diabetesjournals.org/diabetes/article/69/Supplement_1/1830-P/56898/1830-P-Therapeutic-Effect-of-a-Novel-Long-Acting

1830-P: Therapeutic Effect of a Novel Long-Acting GLP-1/GIP ... HM15211 is a novel long-acting GLP-1/GIP/Glucagon triple agonist. Previously, HM15211 treatment improved liver fat and fibrosis in various animal models of ...

4. researchgate.net researchgate.net/publication/345087990_HM15211_a_novel_GLP-1GIPGlucagon_triple-receptor_co-agonist_significantly_reduces_liver_fat_and_body_weight_in_obese_subjects_with_non-alcoholic_fatty_liver_disease_A_Phase_1b2a_multi-center_randomize

HM15211, a novel GLP-1/GIP/Glucagon triple-receptor co ... Phase 1a and 1b studies have shown the drug's effectiveness in lowering body weight and liver fat in obese individuals with non-alcoholic fatty liver disease.

5. sigma.larvol.com sigma.larvol.com/product.php?e1=737663&tab=newstrac

efocipegtrutide (HM15211) News Together with the results in DIO mice, our result suggest that HM15211 may be a novel therapeutic option for NASH and fibrosis by optimally conferring ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04505436

NCT04505436 | Study to Evaluate Efficacy, Safety and ... This study is a phase 2 study to Evaluate Efficacy, Safety and Tolerability of HM15211 Treatment for 12 Months in Subjects with Biopsy Confirmed NASH.