Survodutide for Fatty Liver Disease

Recruiting at 694 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a medicine called survodutide can improve liver function in people with a specific type of fatty liver disease known as MASH (metabolic associated steatohepatitis) who have moderate or advanced liver damage. Participants will be randomly assigned to receive either survodutide or a placebo, which resembles the medicine but contains no active ingredients. The trial is ideal for those with MASH, living with obesity, and diagnosed with moderate or advanced liver fibrosis (a condition where the liver is scarred). Throughout the study, participants will receive dietary and exercise advice and regularly check in with the study team. The aim is to determine if survodutide can effectively and safely improve liver health over time. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

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

Research has shown that survodutide is generally well-tolerated. In a previous study, 25% of healthy individuals and up to 87.5% of those with liver cirrhosis experienced side effects related to the drug after just one dose. While these side effects weren't specified, potential participants should consider them when thinking about joining a trial. Another study found that 83% of adults treated with survodutide showed significant improvements in liver disease caused by MASH, a type of fatty liver disease.

Survodutide is still under investigation, so not all side effects or risks may be known yet. However, the treatment has shown promise in improving liver conditions related to MASH, which is encouraging. Prospective participants should always consult a healthcare provider before joining a clinical trial. They can offer advice tailored to individual health needs. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for fatty liver disease, which often focus on lifestyle changes and medications like vitamin E or pioglitazone, Survodutide offers a new approach. Researchers are excited about Survodutide because it targets the condition with a novel mechanism of action. This drug is designed to potentially reduce liver fat more effectively by acting on a different biological pathway compared to current therapies. This unique action could mean better outcomes for patients who haven't seen significant improvements with existing options.

What evidence suggests that survodutide might be an effective treatment for fatty liver disease?

Research has shown that survodutide, which participants in this trial may receive, may help treat liver disease linked to non-alcoholic steatohepatitis (MASH). In one study, 83% of adults taking survodutide experienced improvements in liver health, particularly in reducing liver scarring. Another study found that 87% of participants had a significant decrease in liver fat, compared to just under 20% who took a placebo. Additionally, survodutide helped lower body weight and improved other signs of liver disease over several weeks. These results suggest that survodutide could effectively improve liver health for people with MASH. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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 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]

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]

Citations

1. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/metabolic-diseases/survodutide-top-line-results-mash-fibrosis

survodutide top-line results MASH fibrosis Survodutide Phase II trial shows 83% of adults treated achieved groundbreaking results in liver disease due to MASH, with significant improvements in fibrosis.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10844353/

a randomised clinical trial - PMC - PubMed Central Survodutide reduced HbA 1c levels and bodyweight after 16 weeks' treatment in participants with type 2 diabetes.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06632444

NCT06632444 | LIVERAGE™: A Study to Test Whether ... 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 ...

4. boehringer-ingelheim.com boehringer-ingelheim.com/human-health/metabolic-diseases/breakthrough-phase-2-survodutide-data-liver-fibrosis-mash

Breakthrough Phase 2 survodutide data liver fibrosis MASH Actual treatment results showed that up to 87.0% of adults achieved at least a 30% relative reduction in liver fat versus 19.7% with placebo, as ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0168827824023031

Efficacy, tolerability and pharmacokinetics of survodutide, a ... Liver fat content, liver stiffness, liver volume, body weight, and other hepatic and metabolic disease markers were generally reduced after 28 weeks of ...

6. journal-of-hepatology.eu journal-of-hepatology.eu/article/S0168-8278(24)02303-1/fulltext

Efficacy, tolerability and pharmacokinetics of survodutide, a ... Drug-related adverse events occurred in 25.0% of healthy individuals and ≤25.0% of those with cirrhosis after single doses, and 82.4% and 87.5%, ...

7. jacc.org jacc.org/doi/10.1016/j.jchf.2024.09.004

Survodutide for the Treatment of Obesity: Rationale and ... SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk.