HM15211 for Non-alcoholic Steatohepatitis (NASH)

Recruiting at 63 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

240 Participants Needed

Trial Summary

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.

What evidence supports the effectiveness of the drug HM15211 for treating non-alcoholic steatohepatitis (NASH)?

The drug HM15211, which is a combination of three agents that mimic natural hormones in the body, has shown promising results in early studies and animal models for reducing liver inflammation and damage in NASH. Additionally, similar drugs targeting the same pathways have been effective in treating related conditions like type 2 diabetes and obesity, which are risk factors for NASH. ^{1 2 3 4 5}

Is HM15211 (Efocipegtrutide) safe for humans?

HM15211 (Efocipegtrutide) has shown manageable toxicity in early studies, meaning it has been generally safe for humans in initial trials. ^{1 2 6 7 8}

What makes the drug HM15211 unique for treating NASH?

HM15211 is unique because it is a triple agonist that targets three different receptors (GLP-1, GIP, and glucagon), which may offer a more comprehensive approach to treating NASH compared to other treatments that typically target only one or two pathways. ^{1 2 6 7 9}

What is the purpose of this trial?

This trial is testing a medication called HM15211 to see if it can help people with a liver disease called NASH. The study will check if the medication is safe and effective over a period of time.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

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]

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 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]

References

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

GLP-1 mimetics as a potential therapy for nonalcoholic steatohepatitis. [2023]

2. United States 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. [2023]

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

Glucagon-like peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Incretin combination therapy for the treatment of non-alcoholic steatohepatitis. [2021]

6. Netherlands 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. [2023]

7. Netherlands 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. [2023]

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

GLP-1/GIP/glucagon receptor triagonism gets its try in humans. [2022]

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

Lysophosphatidic acid receptor 1 antagonist (EPGN2154) causes regression of NASH in preclinical NASH models. [2023]