Resmetirom for Fatty Liver Disease

(MAESTRO-NASH Trial)

Not currently recruiting at 281 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Resmetirom to determine its effectiveness in treating nonalcoholic steatohepatitis (NASH), a type of fatty liver disease that can cause liver damage. Researchers aim to find out if Resmetirom can reduce liver scarring (fibrosis) and prevent disease progression. Participants will receive either 80 mg or 100 mg of Resmetirom daily or a placebo (a harmless pill with no effect) for comparison. Suitable candidates for this trial have been diagnosed with NASH through a liver biopsy and have experienced liver scarring. As a Phase 3 trial, this is the final step before FDA approval, offering a chance to contribute to a potentially groundbreaking treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Resmetirom (MGL-3196) is generally safe and well-tolerated in adults with nonalcoholic steatohepatitis (NASH), a type of fatty liver disease. Studies found that Resmetirom reduced liver fat and improved liver health without causing major side effects. Reports indicate that participants handled both 80 mg and 100 mg doses well. This supports further research on Resmetirom as a treatment for liver issues. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Most treatments for fatty liver disease focus on lifestyle changes or managing symptoms with medications like vitamin E or pioglitazone. But Resmetirom (MGL-3196) works differently, targeting thyroid hormone receptors in the liver to specifically reduce liver fat. Researchers are excited about Resmetirom because it directly addresses liver fat accumulation, offering a more targeted approach than current options. Additionally, its potential for fewer side effects and easier administration with an oral daily dose makes it a promising candidate for improving patient compliance and outcomes.

What evidence suggests that this treatment might be an effective treatment for fatty liver disease?

Research has shown that Resmetirom, also known as MGL-3196, may help treat nonalcoholic steatohepatitis (NASH), a type of fatty liver disease. In studies, 24.2% of patients taking 80 mg of Resmetirom improved in liver fibrosis, meaning their liver scarring got better without worsening other liver problems. Additionally, Resmetirom reduced liver fat by 30% or more, leading to a 37% rate of NASH resolution, indicating less liver inflammation in many patients. In this trial, participants will receive either 80 mg or 100 mg of Resmetirom, or a matching placebo, to further evaluate its effectiveness in treating NASH and improving liver health. ^{3 4 5 6 7}

Who Is on the Research Team?

Rebecca Taub, MD

Principal Investigator

Madrigal Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38324483/

A Phase 3, Randomized, Controlled Trial of Resmetirom in ... Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg ...

2. nejm.org nejm.org/doi/10.1056/NEJMoa2309000

A Phase 3, Randomized, Controlled Trial of Resmetirom in ... Fibrosis improvement by at least one stage with no worsening of the NAFLD activity score was achieved in 24.2% of the patients in the 80-mg ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03900429

NCT03900429 | A Phase 3 Study to Evaluate the Efficacy ... A double-blind placebo controlled randomized Phase 3 study to determine if 80 or 100 mg of MGL-3196 as compared with placebo resolves NASH and/or reduces ...

4. nature.com nature.com/articles/s41591-023-02603-1

Resmetirom for nonalcoholic fatty liver disease Reduction in hepatic fat of ≥30% by resmetirom was associated with an increased rate of NASH resolution (37%) as well as improvements in patient ...

5. icer.org icer.org/wp-content/uploads/2025/01/NASH-Final-Report_Updated_011025.pdf

Resmetirom and Obeticholic Acid for Non-Alcoholic ... There were significant improvements in secondary outcomes including the individual histological measures that are used in the NAS score, MRI- ...

6. ejim.springeropen.com ejim.springeropen.com/articles/10.1186/s43162-025-00468-z

Resmetirom in the management of metabolic associated ... Clinical trials revealed reductions in hepatic fat, improvements in liver fibrosis, and positive effects on metabolic health and quality of life ...

7. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37845512/

Resmetirom for nonalcoholic fatty liver disease These findings demonstrate resmetirom was safe and well tolerated in adults with presumed NASH, supporting a role for further clinical development.