Survodutide for Fatty Liver Disease

Recruiting at 452 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

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) or * A confirmed liver disease called metabolic-associated steatohepatitis (MASH) * BMI of 27 kg/m2 or more or * 25 kg/m2 or more if the participant is Asian. People with a history of other chronic liver diseases or high 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 NASH or MASH improve their 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. All participants regularly receive counselling to make changes to their diet and to exercise regularly. Participants are in the study for up to 4 and a half years. During this time, they visit the study site or have a remote visit by video call every 2, 4 or 6 weeks for about a 1 year and 5 months. After this time participants visit the trial site or have 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 is regularly measured. At some visits the liver parameters are measured using different imaging methods. The participants also fill in questionnaires about their symptoms. The results are compared between the groups to see whether the treatment works.

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.

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

The research mentions that glucagon-like peptide-1 receptor (GLP-1R) agonists, similar to components in Survodutide, have shown promise in improving liver conditions related to fatty liver disease, such as 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 improving liver conditions, with a novel approach that may offer additional benefits for fatty liver disease. Unlike other treatments, it may target multiple pathways involved in the disease, potentially offering a more comprehensive treatment option. ^{1 6 7 8 9}

Eligibility Criteria

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)

I am an adult over 18 or the legal age of consent in my country.

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

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

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)

Treatment Details

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.

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

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 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]

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. 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]

2. 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]

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]