What is the mechanism of action of this treatment?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include GLP-1 receptor agonists and dual GLP-1 and glucagon receptor agonists like cotadutide. GLP-1 receptor agonists improve glycemic control, promote weight loss, and reduce liver fat by enhancing insulin secretion, inhibiting glucagon release, and slowing gastric emptying. Dual GLP-1 and glucagon receptor agonists add the benefit of increased energy expenditure and further reduction of liver fat by activating glucagon receptors. These mechanisms are crucial for NAFLD patients as they target both metabolic dysfunction and hepatic steatosis, addressing the core issues of the disease.

What side effects are associated with this type of intervention?

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) similar to Cotadutide, such as GLP-1 receptor agonists, often have side effects including gastrointestinal issues like nausea, vomiting, and diarrhea. There is also a potential risk for acute pancreatitis and, in rare cases, pancreatic cancer. Other side effects may include injection site reactions and, less commonly, gallbladder-related issues such as cholelithiasis. It is important for patients to discuss these potential risks with their healthcare provider to make an informed decision.

What prior FDA approvals exist?

As of the information provided, there are no specific FDA approvals mentioned for the treatment of Non-alcoholic Fatty Liver Disease (NAFLD) or Non-alcoholic Steatohepatitis (NASH) using dual GLP-1 and glucagon receptor agonists like cotadutide. However, GLP-1 receptor agonists such as liraglutide have shown efficacy in treating NASH, as evidenced by clinical trials. Liraglutide has been used to improve glycemic control and induce weight loss in patients with type 2 diabetes, which can be beneficial for managing NASH.

What other types of research exist?

Promising alternatives to Cotadutide for NAFLD patients include Sodium-Glucose Cotransporter 2 Inhibitors (SGLT2i) like dapagliflozin and Ipragliflozin, and Glucagon-like Peptide-1 (GLP-1) receptor agonists such as liraglutide and semaglutide. These drugs have shown efficacy in improving liver-related outcomes in NAFLD patients.

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Glucagon-Like Peptide-1 (GLP-1) Receptor Agonist

Cotadutide for Non-alcoholic Steatohepatitis with Fibrosis (PROXYMO-ADV Trial)

Phase 2

Waitlist Available

Research Sponsored by AstraZeneca

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Histologically confirmed non-alcoholic steatohepatitis (NASH) per NASH Clinical Research Network (CRN) criteria as diagnosed by histology from a liver biopsy performed ≤ 180 days from randomization and fulfilling specific histological criteria: NAS ≥ 4 with a score of ≥ 1 for each component (steatosis, lobular inflammation, and ballooning), presence of fibrosis stage F2 or F3, Women of childbearing potential, non-pregnant and nonbreastfeeding and using appropriate birth control to avoid pregnancy throughout the study and for up to 4 weeks after the last dose of study intervention.

Males and female participants aged ≥ 18 to ≤ 75 years at the time of signing the informed consent

Must not have

Severely uncontrolled hypertension

Chronic liver disease of other etiologies

Timeline

Screening 3 weeks

Treatment Varies

Follow Up from first dose on day 1 until the follow-up period, 28 days post last dose

Summary

This trial is testing cotadutide, a medication aimed at reducing liver inflammation and scarring, in patients with non-cirrhotic NASH with fibrosis. The study will evaluate the safety and effectiveness of two different doses of the medication. Cenicriviroc (CVC) is another drug that has shown promise in treating NASH and liver fibrosis by inhibiting macrophage accumulation and improving liver fibrosis.

Who is the study for?

Adults aged 18-75 with non-cirrhotic NASH (Non-alcoholic Steatohepatitis) and fibrosis stage F2 or F3 can join this trial. They must have a confirmed diagnosis, not be pregnant or breastfeeding, and use birth control. People with recent cancer, severe allergies to study drugs, bleeding disorders preventing liver biopsy, uncontrolled high blood pressure, certain infections like HIV or hepatitis B/C, history of cirrhosis or significant heart disease are excluded.

What is being tested?

The trial is testing Cotadutide's safety and effectiveness against a placebo in treating NASH with fibrosis. Participants will receive either the drug Cotadutide by injection or a placebo without knowing which one they're getting to compare results fairly.

What are the potential side effects?

Possible side effects of Cotadutide may include reactions at the injection site such as redness or pain, gastrointestinal issues like nausea and vomiting, potential liver-related problems due to its target area of treatment for NASH with fibrosis.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I am between 18 and 75 years old.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My high blood pressure is not under control.

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I have a long-term liver condition not caused by alcohol.

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I have a history of severe liver disease, including signs of increased blood pressure in the liver.

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I cannot safely undergo a liver biopsy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ from first dose on day 1 until the follow-up period, 28 days post last dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~from first dose on day 1 until the follow-up period, 28 days post last dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and from first dose on day 1 until the follow-up period, 28 days post last dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Number of Treatment-induced Anti-Drug Antibody (ADA) participants

Number of participants with abnormal laboratory assessments

Number of participants with abnormal vital signs.

+3 more

Secondary study objectives

Part A: Absolute change from baseline in body weight

Part A: Change from baseline in HbA1c in participants with T2DM

Part A: Percent change from baseline in triglycerides

+11 more

Trial Design

4Treatment groups

Experimental Treatment

Placebo Group

Group I: Cotadutide 600μgExperimental Treatment1 Intervention

Group II: Cotadutide 300μgExperimental Treatment1 Intervention

Group III: Placebo 600μgPlacebo Group1 Intervention

Group IV: Placebo 300μgPlacebo Group1 Intervention

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Cotadutide

Not yet FDA approved

0 / 6Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Common treatments for Non-alcoholic Fatty Liver Disease (NAFLD) include GLP-1 receptor agonists and dual GLP-1 and glucagon receptor agonists like cotadutide. GLP-1 receptor agonists improve glycemic control, promote weight loss, and reduce liver fat by enhancing insulin secretion, inhibiting glucagon release, and slowing gastric emptying. Dual GLP-1 and glucagon receptor agonists add the benefit of increased energy expenditure and further reduction of liver fat by activating glucagon receptors. These mechanisms are crucial for NAFLD patients as they target both metabolic dysfunction and hepatic steatosis, addressing the core issues of the disease.