Resmetirom for Fatty Liver Disease

(MAESTRO-NASH Trial)

Recruiting at 245 trial locations

Overseen By Kimberly Dorney, RN, MSN

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Madrigal Pharmaceuticals, Inc.

Must not be taking: GLP-1 agonists, High-dose Vitamin E

Disqualifiers: Alcohol use, Thyroid diseases, Cirrhosis, 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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: Unknown

Duration: 52 weeks

1759 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are on GLP-1 agonists, high dose Vitamin E, or pioglitazone, you must be on a stable dose for 24 weeks before the biopsy.

What data supports the effectiveness of the drug Resmetirom for treating fatty liver disease?

Research shows that Resmetirom can significantly reduce liver fat and improve liver health in patients with nonalcoholic steatohepatitis (NASH), a type of fatty liver disease. It also helps lower bad cholesterol and triglycerides, which are fats in the blood, making it a promising treatment option. ^{1 2 3 4 5}

Is Resmetirom safe for humans?

Resmetirom has been tested in several studies for nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH), and it was generally found to be safe and well tolerated. Some patients experienced mild side effects like diarrhea and nausea, but these were not serious. ^{1 2 3 4 5}

How is the drug Resmetirom unique for treating fatty liver disease?

Resmetirom is unique because it is an orally administered drug that specifically targets the liver and works by activating thyroid hormone receptors to increase fat metabolism and reduce liver fat, which is different from other treatments that may not target these specific pathways. ^{1 2 3 5 6}

What is the purpose of this trial?

This trial is testing a medication called MGL-3196 to see if it can help treat patients with NASH and liver fibrosis. The medication works by reducing fat and inflammation in the liver, which can help heal and protect it from further damage.

Research Team

Rebecca Taub, MD

Principal Investigator

Madrigal Pharmaceuticals, Inc.

Eligibility Criteria

Adults over 18 with suspected or confirmed NASH and liver fibrosis stages 1A to 3 are eligible for this trial. They must have metabolic risk factors, an AST level above 20 U/L, and evidence of increased liver fat via MRI-PDFF or a biopsy showing NASH within the last 24 weeks. Participants should not have had significant weight changes recently.

Inclusion Criteria

You must be willing to participate in the study and provide written informed consent.

I have been diagnosed with moderate to severe liver fibrosis due to NASH.

Must be willing to participate in the study and provide written informed consent.

Exclusion Criteria

I have recently gained or lost a lot of weight.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 80 or 100 mg of MGL-3196 or placebo daily to assess the effect on NASH and fibrosis

52 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Long-term follow-up

Participants are monitored for long-term outcomes including liver-related events and mortality

up to 54 months

Treatment Details

Interventions

• MGL-3196 (Resmetirom)
• Placebo

Trial Overview The study is testing if MGL-3196 (Resmetirom) at doses of either 80 mg or 100 mg is more effective than a placebo in resolving NASH, reducing liver fibrosis on biopsies, and preventing progression to cirrhosis or advanced liver disease.

Participant Groups

Group I: 100 mg MGL-3196 Active Control 2 Interventions

100 mg daily

Group II: 80 mg MGL-3196 Active Control 2 Interventions

80 mg daily

Group III: Matching Placebo Placebo Group 2 Interventions

Placebo Daily

Who Is Running the Clinical Trial?

Madrigal Pharmaceuticals, Inc.

Lead Sponsor

Trials

16

Recruited

5,400+

Findings from Research

In a 36-week study involving 125 patients with biopsy-confirmed NASH, resmetirom significantly reduced hepatic fat compared to placebo, with a 32.9% reduction at 12 weeks and 37.3% at 36 weeks, indicating its efficacy in treating NASH.

The treatment was generally safe, with most adverse events being mild or moderate; however, there was a higher incidence of mild diarrhea and nausea in patients taking resmetirom.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. Harrison, SA., Bashir, MR., Guy, CD., et al.[2021]

In a 52-week phase 3 trial involving 1,143 adults with presumed NASH, resmetirom was found to be safe and well tolerated, with treatment-emergent adverse events occurring in similar rates compared to placebo.

Resmetirom significantly reduced hepatic fat, LDL-C, apoB, and triglycerides, indicating its potential efficacy in treating nonalcoholic steatohepatitis and supporting further clinical development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. Harrison, SA., Taub, R., Neff, GW., et al.[2023]

In a 36-week study, resmetirom significantly reduced liver fat by an average of 11.1% and showed a 52.3% relative reduction in patients with nonalcoholic steatohepatitis (NASH), indicating its efficacy in treating this condition.

Resmetirom also led to significant reductions in LDL cholesterol, apolipoprotein B, and triglycerides, while markers of liver fibrosis decreased, demonstrating both its safety and potential benefits for liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH. Harrison, SA., Bashir, M., Moussa, SE., et al.[2023]

Resmetirom effectively reduces lipid accumulation and triglyceride levels in both in vitro NASH cell models and in vivo NASH mouse models, indicating its potential as a treatment for non-alcoholic steatohepatitis (NASH).

The mechanism of action involves the recovery of RGS5 expression and the inhibition of the STAT3 and NF-κB signaling pathways, which are activated in NASH, suggesting that resmetirom targets specific molecular pathways to improve liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner. Wang, X., Wang, L., Geng, L., et al.[2023]

Resmetirom (MGL-3196) is a promising treatment for nonalcoholic steatohepatitis (NASH) that has shown potential cost-effectiveness, with an incremental cost-effectiveness ratio of $53,929 per quality-adjusted life-year (QALY) gained, based on a model informed by a phase II clinical trial.

The use of resmetirom could significantly reduce serious liver-related complications, such as decompensated cirrhosis, hepatocellular carcinoma, and the need for liver transplants, indicating its efficacy in improving long-term health outcomes for patients with NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early Cost-Effectiveness and Price Threshold Analyses of Resmetirom: An Investigational Treatment for Management of Nonalcoholic Steatohepatitis. Javanbakht, M., Fishman, J., Moloney, E., et al.[2023]

In a Phase 2 trial, resmetirom significantly reduced liver fat and resolved non-alcoholic steatohepatitis (NASH) without worsening fibrosis, indicating its potential efficacy as a treatment for this condition.

The ongoing Phase 3 MAESTRO clinical program aims to further evaluate resmetirom's safety and effectiveness in up to 2000 adults with NASH, using liver biopsies and non-invasive tests to assess outcomes over a 54-week period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. Harrison, SA., Ratziu, V., Anstee, QM., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Resmetirom (MGL-3196) for the treatment of non-alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 trial. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Resmetirom for nonalcoholic fatty liver disease: a randomized, double-blind, placebo-controlled phase 3 trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Effects of Resmetirom on Noninvasive Endpoints in a 36-Week Phase 2 Active Treatment Extension Study in Patients With NASH. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Resmetirom Ameliorates NASH-Model Mice by Suppressing STAT3 and NF-κB Signaling Pathways in an RGS5-Dependent Manner. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Early Cost-Effectiveness and Price Threshold Analyses of Resmetirom: An Investigational Treatment for Management of Nonalcoholic Steatohepatitis. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Design of the phase 3 MAESTRO clinical program to evaluate resmetirom for the treatment of nonalcoholic steatohepatitis. [2023]