Survodutide for Fatty Liver Disease

Recruiting at 512 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Must not be taking: Obesity medications

Disqualifiers: Other liver diseases, Liver cirrhosis, Hepatocellular carcinoma, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

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

Compensation: Varies

Number of Visits: 8

1800 Participants Needed

Trial Summary

What is the purpose of this trial?

This study is open to adults who are at least 18 years old and have: * a confirmed liver disease called non-alcoholic steatohepatitis (NASH)/metabolic-associated steatohepatitis (MASH) and * moderate or advanced liver fibrosis People with a history of acute or chronic liver diseases other than MASH or chronic alcohol intake cannot take part in this study. The purpose of this study is to find out whether a medicine called survodutide helps people with MASH and moderate or advanced liver fibrosis improve their liver function. This study has 2 parts. The purpose of the first part of this study is to find out the effect of survodutide on MASH and liver fibrosis. The purpose of the second part is to find out how safe and effective survodutide is in improving liver function. Participants are put into 2 groups randomly, which means by chance. 1 group gets survodutide and 1 group gets placebo. Placebo looks like survodutide but does not contain any medicine. Each participant has twice the chance of getting survodutide. Participants and doctors do not know who is in which group. Participants inject survodutide or placebo under their skin once a week. The survodutide doses are slowly increased until the target dose is reached. All participants receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for up to 7 years. During this time, they regularly visit the study site or have remote visits by video call. For about the first year of the study, participants have these visits every 2 weeks, increasing to every 4 weeks and then every 6 weeks. After being in the study for a little over a year participants will then alternate between visiting the study site or having a remote visit every 3 months until the end of the study. The doctors check participants' health and take note of any unwanted effects. The participants' body weight and effects on the stomach and intestines are regularly measured. At some visits the liver is measured using different imaging methods. At 2 or 3 visits doctors take a small sample of liver tissue (biopsy). The participants also fill in questionnaires about their symptoms and quality of life. The results are compared between the groups to see whether the treatment works.

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

The trial information does not specify if you need to stop taking your current medications. However, it does mention that you cannot have been treated with any medication for obesity within 3 months before the screening biopsy. It's best to discuss your specific medications with the trial team.

What evidence supports the effectiveness of the drug Survodutide for treating fatty liver disease?

While there is no direct evidence for Survodutide, similar drugs like GLP-1 receptor agonists (such as liraglutide and semaglutide) have shown promise in improving liver conditions related to fatty liver disease by reducing liver fat and improving liver inflammation. ^{1 2 3 4 5}

How is the drug Survodutide different from other treatments for fatty liver disease?

Survodutide is unique because it combines the effects of glucagon-like peptide-1 receptor agonists, which have shown promise in treating non-alcoholic fatty liver disease by improving liver health and reducing fat content. Unlike other treatments, Survodutide may offer a novel approach by potentially targeting multiple pathways involved in the disease. ^{2 6 7 8 9}

Eligibility Criteria

Adults over 18 with MASH (a type of non-alcoholic fatty liver disease) and moderate to advanced fibrosis confirmed by a biopsy can join. They must not have other chronic liver diseases or a history of heavy alcohol use, maintain stable body weight, and keep consistent diet and exercise during the trial.

Inclusion Criteria

Further inclusion criteria apply

I am at least 18 years old or of legal age in my country.

My weight has been stable, with less than a 5% change in the last 3 months.

Exclusion Criteria

I have had or am planning to have a liver transplant.

I have a history of serious liver problems.

I have liver disease, but it's not MASH.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment Part 1

Participants receive weekly injections of survodutide or placebo to evaluate the effect on MASH and liver fibrosis. Doses are gradually increased to the target dose.

52 weeks

Every 2 weeks for the first year, then every 4 weeks

Treatment Part 2

Continued weekly injections to assess the long-term safety and efficacy of survodutide in improving liver function.

Up to 7 years

Every 6 weeks, then every 3 months alternating between in-person and remote visits

Follow-up

Participants are monitored for safety and effectiveness after treatment, including health checks, body weight, and liver imaging.

4 weeks

Treatment Details

Interventions

• Survodutide

Trial Overview The LIVERAGE™ study is testing if Survodutide improves liver function in MASH patients with fibrosis. Participants are randomly assigned to receive either Survodutide or placebo via weekly injections, with double the chance of receiving Survodutide. The study spans up to 7 years with regular health checks.

Participant Groups

Group I: Survodutide Experimental Treatment 1 Intervention

Group II: Placebo Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

Boehringer Ingelheim

Lead Sponsor

Trials

2,566

Recruited

16,150,000+

Findings from Research

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

A systematic review of 25 trials involving 2597 adults found that PPAR agonists and GLP-1R agonists significantly improved liver histology in patients with non-alcoholic fatty liver disease (NAFLD), indicating their potential as effective treatments.

SGLT2 inhibitors were shown to reduce liver fat content, further supporting their role in managing NAFLD, especially in individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. Mantovani, A., Byrne, CD., Targher, G.[2022]

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 of 85 patients with type 2 diabetes and non-alcoholic fatty liver disease, liraglutide and metformin were found to significantly reduce body fat mass and promote weight loss over 24 weeks, while gliclazide showed no significant changes in weight or fat mass.

Both liraglutide and metformin improved blood glucose control and liver function markers more effectively than gliclazide, indicating they may be better treatment options for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial. Feng, WH., Bi, Y., Li, P., et al.[2023]

Non-alcoholic fatty liver disease (NAFLD) is a growing global health issue linked to metabolic disorders, with significant risks for disease progression and mortality, yet there are currently no approved medications for its treatment.

This paper reviews emerging therapeutic strategies and potential drug targets for NAFLD, emphasizing the importance of ongoing clinical trials in developing effective pharmacotherapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. Prikhodko, VA., Bezborodkina, NN., Okovityi, SV.[2023]

In an 8-week study with obese mice, the new sustained-release formulation of exenatide, DA-3091, significantly reduced body weight gain more effectively than the obesity drug sibutramine, indicating its potential as a weight management treatment.

DA-3091 also showed promise in treating non-alcoholic fatty liver disease (NAFLD) by significantly lowering liver injury markers (ALT and AST) and reducing hepatic lipid accumulation in mice, suggesting its efficacy in addressing metabolic diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a new sustained-release microsphere formulation of exenatide, DA-3091, on obese and non-alcoholic fatty liver disease mice. Son, JP., Son, MK., Jun, SW., et al.[2018]

Thiazolidinediones, a type of insulin-sensitizing agent, have been shown to effectively reduce liver fat and cellular injury in patients with nonalcoholic fatty liver disease (NAFLD), although they may cause weight gain due to increased peripheral fat.

Metformin, another insulin-sensitizing agent, improves biochemical markers in NAFLD without causing weight gain, but its effects on liver histology are more variable, indicating both agents could be beneficial in managing NAFLD despite not being FDA approved.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapy of NAFLD: insulin sensitizing agents. Caldwell, SH., Argo, CK., Al-Osaimi, AM.[2019]

Pioglitazone has shown significant histological improvement in patients with non-alcoholic steatohepatitis (NASH) associated with type 2 diabetes, with benefits observed within 6 months and lasting for at least 3 years, suggesting it may become the standard treatment for this condition.

Emerging treatments, such as glucagon-like peptide 1 receptor agonists, along with ongoing development of various agents targeting different pathways, indicate a promising future for combination therapies in managing NASH and improving patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of patients with type 2 diabetes and non-alcoholic fatty liver disease: current approaches and future directions. Cusi, K.[2022]

In a phase 1 study involving 20 participants (10 with severe renal impairment and 10 healthy controls), firsocostat showed a 40% higher plasma exposure in those with renal impairment, but this increase was not considered clinically significant.

Cilofexor's exposure levels remained unchanged in participants with severe renal impairment compared to healthy controls, suggesting that neither drug requires dosage adjustments for patients with kidney issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Renal Impairment on the Pharmacokinetics of Firsocostat, an Acetyl-Coenzyme A Carboxylase Inhibitor, and Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist. Weber, E., Younis, IR., Nelson, C., et al.[2023]

References

1. France pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. [2023]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Efficacy of peroxisome proliferator-activated receptor agonists, glucagon-like peptide-1 receptor agonists, or sodium-glucose cotransporter-2 inhibitors for treatment of non-alcoholic fatty liver disease: a systematic review. [2022]

3. 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]

4. Japan pubmed.ncbi.nlm.nih.gov

Effects of liraglutide, metformin and gliclazide on body composition in patients with both type 2 diabetes and non-alcoholic fatty liver disease: A randomized trial. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Pharmacotherapy for Non-Alcoholic Fatty Liver Disease: Emerging Targets and Drug Candidates. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

Effects of a new sustained-release microsphere formulation of exenatide, DA-3091, on obese and non-alcoholic fatty liver disease mice. [2018]

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

Therapy of NAFLD: insulin sensitizing agents. [2019]

8. Germany pubmed.ncbi.nlm.nih.gov

Treatment of patients with type 2 diabetes and non-alcoholic fatty liver disease: current approaches and future directions. [2022]

9. England pubmed.ncbi.nlm.nih.gov

Effect of Renal Impairment on the Pharmacokinetics of Firsocostat, an Acetyl-Coenzyme A Carboxylase Inhibitor, and Cilofexor, a Selective Nonsteroidal Farnesoid X Receptor Agonist. [2023]