BI456906 for Fatty Liver Disease

No longer recruiting at 217 trial locations

Overseen By Boehringer Ingelheim

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Boehringer Ingelheim

Must not be taking: Liver injury drugs

Disqualifiers: Alcohol use, Chronic liver disease, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 48 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment, BI 456906 (also known as Survodutide or EX-A7878), for individuals with nonalcoholic steatohepatitis (NASH), a liver disease that includes liver fibrosis (scarring). The goal is to determine if this medication can improve these conditions by testing three different doses against a placebo (a treatment with no active medication). Participants must have a diagnosis of NASH and liver fibrosis, along with a stable body weight. During the trial, participants will receive weekly injections and undergo various health checks, including liver biopsies and imaging tests. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial protocol does not specify if you must stop taking your current medications, but it excludes those who have taken medications associated with liver injury or steatohepatitis within 12 weeks before the trial. It's best to discuss your current medications with the trial doctors to see if they might interfere with the study.

Is there any evidence suggesting that BI 456906 is likely to be safe for humans?

Research shows that survodutide (BI 456906) has been tested in earlier studies and demonstrated promising safety results. In these studies, side effects related to the drug appeared in about 25% of healthy individuals and up to 87.5% of those with liver conditions, typically mild to moderate in severity.

Survodutide has also been used in trials for other conditions, such as type 2 diabetes, where it helped reduce blood sugar levels and body weight. Although safety data is still being gathered, survodutide's progression to this stage suggests it is generally well-tolerated. Participants should find these findings encouraging, though individual experiences may vary. Discuss any concerns or questions with the study team. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for NASH?

Most treatments for fatty liver disease focus on lifestyle changes and medications like vitamin E and pioglitazone. However, Survodutide, the active ingredient in BI 456906, is unique because it targets a different pathway by mimicking the action of a naturally occurring hormone involved in regulating appetite and metabolism. Researchers are excited about Survodutide because it may offer a more direct approach to reducing liver fat and improving liver health. Unlike current treatments, which often require long-term lifestyle changes, Survodutide has the potential to work more efficiently through its novel mechanism of action. Additionally, with multiple dosage options (2.4 mg, 4.8 mg, and 6.0 mg), it allows for a tailored approach to treatment.

What evidence suggests that BI 456906 might be an effective treatment for NASH?

Research has shown that Survodutide (BI 456906), which participants in this trial may receive, may help treat liver disease caused by NASH (nonalcoholic steatohepatitis). In studies, up to 87% of adults who took Survodutide experienced at least a 30% reduction in liver fat, compared to only 19.7% who took a placebo (a substance with no active drug). Additionally, 83% of participants showed significant improvements in liver fibrosis, which is scarring of the liver. These findings suggest that Survodutide could effectively improve liver health in people with NASH. The treatment might also help some patients lose weight and lower their blood sugar levels. ^{1 2 3 4 6}

Are You a Good Fit for This Trial?

Inclusion Criteria

Diagnosis of non-alcoholic steatohepatitis (NASH) (Non-alcoholic Fatty Liver Disease (NAFLD) Activity Score (NAS) ≥ 4, with at least 1 point in inflammation and ballooning each) and fibrosis stage F1-F3 proven by a biopsy conducted during the screening period or by a historical biopsy conducted within the last 6 months prior to randomization and stable body weight defined as less than 5% self-reported change in body weight between the historical biopsy and randomization, if a historical biopsy is used.

Liver fat fraction ≥ 8% measured by Magnetic Resonance Imaging (MRI)-Proton Density Fat Fraction (PDFF) and liver stiffness > 6.0 kPa measured by FibroScan® at Visit 1 (if biopsy is scheduled during the screening period MRI-PDFF and FibroScan® assessments have to be performed prior to the biopsy). However, the diagnosis of NASH and fibrosis at liver biopsy (including historical biopsy) is the primary assessment to establish patient eligibility.

Patients willing and able to undergo liver biopsies per protocol as judged by the Investigator.

Exclusion Criteria

Current or history of significant alcohol consumption (defined as intake of > 210 g/ week in males and > 140 g/ week in females on average over a consecutive period of more than 3 months) or inability to reliably quantify alcohol consumption based on Investigator judgement within the last 5 years.

Intake of medications historically associated with liver injury, hepatic steatosis or steatohepatitis within 12 weeks prior to Visit 1. Intake of restricted medications or any medications considered likely to interfere with the safe conduct of the trial.

History of other forms of chronic liver disease (e.g., viral hepatitis, autoimmune liver disease, primary biliary sclerosis, primary sclerosing cholangitis, Wilson's disease, hemochromatosis, Alpha-1 Antitrypsin (A1At) deficiency, history of liver transplantation). Hepatitis B and C testing will be done at Visit 1. Patients with positive Hepatitis B surface antigen (HBsAg) should be excluded. Patients treated for hepatitis C must have a negative RNA test at screening and also be Hepatitis C Virus (HCV) RNA negative for at least 3 years prior to screening in order to be eligible for the trial.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive weekly subcutaneous injections of BI 456906 or placebo for 48 weeks

48 weeks

Several in-person visits and some video calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

8 weeks

What Are the Treatments Tested in This Trial?

Interventions

• BI 456906
• Placebo

How Is the Trial Designed?

Group I: Survodutide 6.0 mg - planned maintenance treatment Experimental Treatment 1 Intervention

Group II: Survodutide 4.8 mg - planned maintenance treatment Experimental Treatment 1 Intervention

Group III: Survodutide 2.4 mg - planned maintenance treatment Experimental Treatment 1 Intervention

Group IV: Placebo - planned maintenance treatment 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]

Robuvit® supplementation for 3 months in patients with non-alcoholic fatty liver disease (NAFLD) significantly improved liver function markers, including decreased levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), indicating better hepatic metabolism.

The study, involving 34 subjects, showed that Robuvit® was well-tolerated with no side effects, and it also led to a significant reduction in liver size and echogenicity, suggesting a prevention of progression to liver fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Robuvit® on the progression of non-alcoholic fatty liver disease. Belcaro, G., Cox, DM., Cesarone, MR., et al.[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]

Statins, particularly atorvastatin, have shown promising results in improving liver health and reducing cardiovascular disease (CVD) risk in patients with non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), based on analyses of over 11,000 participants from randomized controlled trials.

Statin treatment not only improves liver enzyme levels and liver imaging results but also significantly reduces CVD morbidity and mortality, with statin-treated NAFLD/NASH patients experiencing a 50% reduction in CVD events compared to those with normal liver function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Statins: An Under-Appreciated Asset for the Prevention and the Treatment of NAFLD or NASH and the Related Cardiovascular Risk. Athyros, VG., Boutari, C., Stavropoulos, K., et al.[2022]

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. 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 ...

3. 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.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06066515?intr=Survodutide&rank=10

NCT06066515 | A Study to Test Whether Survodutide (BI ... The purpose of this study is to find out whether a medicine called survodutide (BI 456906) helps people living with overweight or obesity to lose weight.

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. anzctr.org.au anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381053

ANZCTR - Registration A study to test the effect of different doses of BI 456906 in people with a liver disease called non-alcoholic steatohepatitis (NASH) and liver fibrosis.