Survodutide for Fatty Liver Disease

Recruiting at 609 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Boehringer Ingelheim

Disqualifiers: Chronic liver diseases, Hepatitis B, Hepatitis C, 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: 5

Duration: 1 year and 5 months

1590 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a medicine called survodutide can improve liver function in individuals with a type of liver disease known as NASH or MASH. Participants will receive either survodutide or a placebo, which looks identical but contains no active medicine. The study also includes counseling on diet and exercise to help manage the condition. This trial is suitable for adults with confirmed NASH or MASH and a BMI of at least 27 (or 25 if Asian). Participants with other chronic liver diseases or high alcohol intake are not eligible. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial doctors to get a clear answer.

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

Research has shown that survodutide is generally well-tolerated. In one study, 83% of adults with liver disease due to MASH (a type of fatty liver disease) experienced significant improvements in liver scarring. However, survodutide can cause side effects. Up to 25% of healthy individuals and those with liver damage reported side effects after receiving single doses. This trial is in a later phase, providing more safety information than earlier phases. It is important to discuss possible side effects with the study team or a doctor before joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Unlike standard treatments for fatty liver disease, which often focus on lifestyle changes and medications like vitamin E and pioglitazone, Survodutide offers a new approach by targeting the GLP-1 receptor and glucagon receptor pathways. This dual action can help reduce liver fat more effectively and potentially improve liver function. Researchers are excited about Survodutide because it may provide a more direct and efficient way to tackle the underlying causes of fatty liver disease, offering hope for better outcomes where current options have limitations.

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 diseases like MASH (metabolic-associated steatohepatitis) and NASH (non-alcoholic steatohepatitis). In one study, 83% of people with MASH showed significant improvements in liver scarring. Another study found that people taking survodutide experienced a substantial drop in liver fat, with up to 87% seeing at least a 30% decrease. Survodutide also lowers blood sugar and body weight in people with type 2 diabetes. These findings suggest that survodutide could improve liver function and overall health in people with these liver conditions. ^{1 2 5 6 7}

Are You a Good Fit for This Trial?

Adults over 18 with NASH or MASH cirrhosis, a BMI of at least 27 kg/m2 (25 kg/m2 for Asians), and certain liver fat measurements can join this trial. Those with other chronic liver diseases or high alcohol intake are excluded.

Inclusion Criteria

Magnetic resonance imaging proton density fat fraction (MRI-PDFF) fat fraction ≥5% or FibroScan® with controlled attenuation parameter (CAP) ≥288 dB/m, obtained during the screening period or a historic MRI-PDFF or FibroScan® with CAP ≤12 weeks prior to randomisation (except for patients with 'cryptogenic cirrhosis' where MRI-PDFF <5% or FibroScan® with CAP <288 dB/m is allowed). This inclusion criterion does not apply for participants with a recent (≤12 months prior to randomisation) liver biopsy showing steatosis/steatohepatitis)

Body mass index (BMI) ≥27 kg/m2 (≥25 kg/m2 for Asian trial participants)

Further inclusion criteria apply

Exclusion Criteria

Any of the following lab test result at screening: Albumin below <3.5 g/dL (<35.0 g/L), International normalised ratio (INR) >1.3 unless due to therapeutic anticoagulants, Total bilirubin (TBL) >1.2x upper limit of normal (ULN) NOTE: Trial participants with Gilbert Syndrome are eligible with a TBL >1.2x ULN if reticulocyte count is within normal limits, haemoglobin is within normal limits unless due to chronic anaemia and unrelated to hemolysis, and direct bilirubin is <20% of TBL, Alkaline phosphatase >1.5x ULN, Platelet count <100,000/µL (<100 GI/L)

My liver disease severity score is above 12.

I have had a liver transplant or am on the waiting list for one.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive survodutide or placebo injections once a week, with regular counselling for diet and exercise

1 year and 5 months

Visits every 2, 4, or 6 weeks (in-person or remote)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with health checks and liver parameter measurements

3 years

Visits every 3 months (in-person or remote)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo matching survodutide
• Survodutide

Trial Overview The study tests if survodutide improves liver function in people with NASH/MASH cirrhosis. Participants are randomly assigned to receive either survodutide or placebo weekly, while also getting diet and exercise counseling.

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

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]

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 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]

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]

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]

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.