Resmetirom for Non-alcoholic Fatty Liver Disease

Not currently recruiting at 72 trial locations

Overseen By Edward Chiang

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Madrigal Pharmaceuticals, Inc.

Disqualifiers: Alcohol use, Carcinomas, Chronic liver diseases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a medication called Resmetirom (also known as Rezdiffra or MGL-3196) to assess its safety and tolerability for people with non-alcoholic fatty liver disease (NAFLD). NAFLD occurs when fat accumulates in the liver without alcohol as a cause, potentially leading to liver damage over time. The trial includes different groups receiving varying doses of the medication over a year. Suitable candidates are those who have participated in certain previous studies or have liver issues related to NAFLD but do not have other liver diseases or a history of heavy drinking. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the study team or your doctor.

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

Research has shown that resmetirom is generally safe for people. Studies have found that adults with liver disease, such as NASH, tolerate it well. These studies have reported no major safety issues, indicating it is safe enough for further testing.

The FDA has also approved resmetirom for another condition, suggesting it has been found safe in other contexts. While this does not guarantee safety for everyone, it is a positive sign.

Overall, evidence suggests resmetirom is a promising treatment with a good safety record so far. However, discussing potential risks with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for non-alcoholic fatty liver disease?

Resmetirom is unique because it targets thyroid hormone receptors specifically in the liver, aiming to reduce liver fat more effectively than current treatments. Unlike most treatments for non-alcoholic fatty liver disease (NAFLD) that primarily focus on lifestyle changes like diet and exercise, Resmetirom directly addresses the metabolic processes that contribute to liver fat accumulation. Researchers are particularly excited because this targeted approach could lead to a significant reduction in liver fat and inflammation, potentially slowing or even reversing disease progression. The possibility of a medication that works at the cellular level to combat liver fat is a promising advancement over more general treatments.

What evidence suggests that this trial's treatments could be effective for non-alcoholic fatty liver disease?

Studies have shown that resmetirom can significantly reduce liver fat in people with non-alcoholic fatty liver disease (NAFLD). A reduction of at least 30% in liver fat is linked to a higher chance of resolving non-alcoholic steatohepatitis (NASH), a more severe form of NAFLD. Research indicates that resmetirom also helps lower bad cholesterol (LDL) and other harmful fats in the blood. Additionally, it has been associated with noticeable weight loss. This trial will evaluate various dosages of resmetirom—40 mg, 80 mg, and 100 mg—in different treatment arms to further assess its potential for improving liver health and related conditions. ^{3 4 6 7 8}

Who Is on the Research Team?

Rebecca Taub, MD

Principal Investigator

Madrigal Pharmaceuticals, Inc.

Are You a Good Fit for This Trial?

This trial is for patients with a specific liver condition called Non-alcoholic Fatty Liver Disease (NAFLD) who have already completed the MAESTRO-NAFLD-1 study. They must have certain levels of liver scarring and inflammation but cannot have severe liver conditions like cancer, significant alcohol use in the past year, autoimmune diseases, or other health issues that could affect their participation.

Inclusion Criteria

Must provide written informed consent for MAESTRO-NAFLD-OLE and must have screened and met all eligibility requirements for MAESTRO-NASH within 90 days of the Extension Day 1 visit for MAESTRO-NAFLD-OLE and have a liver biopsy that is ineligible for MAESTRO-NASH within 6 months of the Extension Day 1 visit. Eligible liver biopsy for MAESTRO-NAFLD-OLE must have one of the following results: NAS = 3, steatosis 1, ballooning 1, inflammation 1 with F2 or F3 NAS = 3, ballooning 0 with F2 or F3 NAS ≥ 4, at least 1 in all NAS components, F1A or F1C, PRO-C3 ≤ 14 (NASH, but ineligible for MAESTRO-NASH)

NAS = 3, ballooning 0 with F2 or F3

NAS ≥ 4, at least 1 in all NAS components, F1A or F1C, PRO-C3 ≤ 14 (NASH, but ineligible for MAESTRO-NASH)

Exclusion Criteria

I have a long-term liver condition.

You have an ongoing autoimmune disease (a condition where the body's immune system attacks its own cells).

You have any other medical condition that could make it difficult for you to follow the study requirements or affect your health during the study.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Double-blind Treatment

Participants receive double-blind resmetirom 80 mg or 100 mg daily for the first 12 weeks

12 weeks

Open-label Treatment

Participants receive open-label resmetirom 100 mg daily for weeks 12-52

40 weeks

Open-label Extension

Participants, including those with NASH cirrhosis, may receive open-label resmetirom for an additional 52 to 104 weeks

52-104 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Resmetirom

Trial Overview The trial is testing Resmetirom taken orally once daily for 52 weeks to see how safe it is and what its effects are on biomarkers in patients with NAFLD. It's an open-label extension which means everyone gets the active drug and knows what they're taking.

How Is the Trial Designed?

Group I: Open-label Experimental Treatment 1 Intervention

For patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for an additional 52 weeks (ie, 52 weeks in MGL-3196-14 and 104 weeks in MGL-3196-18).

Group II: Open-Label 80 mg Experimental Treatment 1 Intervention

For patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for 104 weeks

Group III: Open-Label 40 mg Experimental Treatment 1 Intervention

For NASH cirrhosis patients who enter MGL-3196-18 directly or were screen failures from MGL-3196-19, open-label resmetirom 40 mg for 104 weeks

Group IV: Open Label 100 mg Experimental Treatment 1 Intervention

For patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks

Group V: Double-blind 80 mg Daily Experimental Treatment 1 Intervention

For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52

Group VI: Double-blind 100 mg Daily Experimental Treatment 1 Intervention

For patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52

Resmetirom is already approved in United States for the following indications:

Approved in United States as Rezdiffra for:

• Noncirrhotic nonalcoholic steatohepatitis with moderate to advanced liver fibrosis (consistent with stages F2 to F3 fibrosis)

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]

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 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 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 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]

Citations

1. 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10258622/

Resmetirom - PubMed Central - NIH Key secondary endpoints included the proportion of patients who had achieved a reduction in hepatic fat of ≥30% at 12 and 36 weeks on MRI-PDFF, and critical ...

3. ir.madrigalpharma.com ir.madrigalpharma.com/news-releases/news-release-details/positive-topline-phase-3-maestro-nafld-1-data-demonstrate

Positive Topline Phase 3 MAESTRO-NAFLD-1 Data ... Resmetirom provided significant reductions in liver fat as measured by MRI-PDFF and reduced atherogenic lipids, including LDLc, apolipoprotein B and ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1590865824007229

Breakthrough in the Treatment of Metabolic Associated ... Also this drug was highly effective in promoting a massive weight loss, ranging up to 20.9% after 72 weeks with the higher dosage [43], with a safety profile ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT04197479

NCT04197479 | A Phase 3 Study to Evaluate Safety and ... The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in hepatic fat fraction as determined by MRI-PDFF ...

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

Resmetirom in the management of metabolic associated ... Resmetirom is a recently approved FDA drug for MASH. It targets multiple pathways involved in the disease, including fat metabolism, inflammation, and fibrosis.

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.

8. journals.lww.com journals.lww.com/hep/fulltext/2025/01000/resmetirom_therapy_for_metabolic.28.aspx

Resmetirom therapy for metabolic dysfunction-associated... Resmetirom received accelerated approval from the United States Food and Drug Administration (FDA) in March 2024 for the treatment of metabolic dysfunction- ...