What is the mechanism of action of this treatment?

Common treatments for Nonalcoholic Steatohepatitis (NASH) target key pathogenic mechanisms such as lipid metabolism, inflammation, and fibrosis. Thyroid Hormone Receptor-Beta (TRβ) agonists like Resmetirom work by enhancing lipid metabolism, reducing liver fat, and improving liver function. This is crucial for NASH patients as it directly addresses the accumulation of fat in the liver, a primary cause of the disease. Additionally, treatments that reduce inflammation and fibrosis help prevent the progression of liver damage, thereby improving clinical outcomes and quality of life for patients with NASH.

What side effects are associated with this type of intervention?

Common treatments for Nonalcoholic Steatohepatitis (NASH) include weight loss, insulin resistance medications, and experimental drugs like Resmetirom (a Thyroid Hormone Receptor-Beta Agonist). Resmetirom and similar agents may cause side effects such as gastrointestinal issues, fatigue, headache, and nausea. Other treatments like vitamin E supplements can increase the risk of death at high doses, and insulin resistance drugs may have their own specific side effects. Overall, the side effects vary depending on the treatment but often include gastrointestinal discomfort and metabolic disturbances.

What prior FDA approvals exist?

As of now, there are no FDA-approved treatments specifically targeting Thyroid Hormone Receptor-Beta (THR-β) for Nonalcoholic Steatohepatitis (NASH). Resmetirom, a liver-directed selective THR-β agonist, is currently under investigation in clinical trials for its potential benefits in treating NASH. Other treatments for NASH focus on lifestyle modifications, managing comorbidities, and off-label use of medications such as pioglitazone and vitamin E, but these are not specifically approved for NASH by the FDA.

What other types of research exist?

Promising novel alternatives to Resmetirom for NASH patients include: <ol> <li>Obeticholic Acid: A farnesoid X receptor (FXR) agonist that has shown efficacy in reducing fibrosis in NASH patients.</li> <li>Elafibranor: A dual PPAR alpha/delta agonist that targets metabolic, inflammatory, and fibrotic pathways in NASH.</li> <li>Lanifibranor: A pan-PPAR agonist that has demonstrated significant improvements in liver histology in NASH patients.</li> <li>Aramchol: A stearoyl-CoA desaturase 1 (SCD1) modulator that reduces liver fat content and inflammation.</li> <li>Cenicriviroc: A CCR2/CCR5 antagonist that targets inflammation and fibrosis in NASH.</li> </ol>

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Thyroid Hormone Receptor Agonist

Resmetirom for NASH Cirrhosis

Phase 3

Recruiting

Research Sponsored by Madrigal Pharmaceuticals, Inc.

Eligibility Criteria Checklist

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

Must have

Definitive (by histologic documentation) or probable NASH as causative agent for cirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum Consensus Definitions for Clinical Trials.

Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (score of 5-6) (no history of hepatic decompensation event).

Must not have

Participants with a chronic liver diseases other than NASH cirrhosis, such as primary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, Hepatitis C, history or evidence of current active autoimmune hepatitis, history or evidence of Wilson's disease, history or evidence of alpha-1-antitrypsin deficiency, history or evidence of genetic hemochromatosis (hereditary, primary), evidence of drug-induced liver disease, as defined on the basis of typical exposure and history, known bile duct obstruction, or suspected or confirmed liver cancer, are excluded.

Participants with a history of hepatic decompensation or impairment are excluded.

Timeline

Screening 3 weeks

Treatment Varies

Follow Up baseline up to month 36

Awards & highlights

Pivotal Trial

Summary

This trial tests a daily pill called resmetirom for people with a stable form of liver disease not caused by alcohol. The goal is to see if the drug can improve liver function and reduce liver fat, thereby preventing serious complications. Resmetirom has been tested in previous studies for the treatment of liver disease.

Who is the study for?

This trial is for adults with well-compensated NASH cirrhosis, confirmed by biopsy or MRI-PDFF. They should have a Child-Pugh A score and no history of hepatic decompensation. Participants must not have other chronic liver diseases or a MELD score ≥12.

What is being tested?

The study tests if taking Resmetirom (80 mg daily) affects the time until patients with NASH cirrhosis experience significant health events compared to a placebo group. It's an oral medication given once per day.

What are the potential side effects?

While specific side effects are not listed here, common ones associated with treatments for liver conditions may include gastrointestinal issues, fatigue, headache, itching, and potential changes in liver enzymes.

Eligibility Criteria

Inclusion Criteria

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

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My cirrhosis is caused by NASH, confirmed through tests.

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My liver disease is stable with a low risk score and no history of severe liver failure.

Exclusion Criteria

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

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I do not have any liver conditions other than NASH cirrhosis.

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I have never had liver failure or serious liver problems.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ baseline up to month 36

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~baseline up to month 36

This trial's timeline: 3 weeks for screening, Varies for treatment, and baseline up to month 36 for reporting.

Treatment Details

Study Objectives

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

Primary study objectives

Incidence Of adjudicated Composite Clinical Outcome event

Awards & Highlights

Pivotal Trial

The final step before approval, pivotal trials feature drugs that have already shown basic safety & efficacy.

Trial Design

2Treatment groups

Active Control

Placebo Group

Group I: ResmetiromActive Control1 Intervention

80 mg daily

Group II: PlaceboPlacebo Group2 Interventions

matching placebo daily

0 / 4Eligibility 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 Nonalcoholic Steatohepatitis (NASH) target key pathogenic mechanisms such as lipid metabolism, inflammation, and fibrosis. Thyroid Hormone Receptor-Beta (TRβ) agonists like Resmetirom work by enhancing lipid metabolism, reducing liver fat, and improving liver function. This is crucial for NASH patients as it directly addresses the accumulation of fat in the liver, a primary cause of the disease. Additionally, treatments that reduce inflammation and fibrosis help prevent the progression of liver damage, thereby improving clinical outcomes and quality of life for patients with NASH.

Current and Emerging Therapies for Non-alcoholic Fatty Liver Disease.Thyroid hormone analogues and derivatives: Actions in fatty liver.