Resmetirom for Non-alcoholic Fatty Liver Disease

Recruiting at 54 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

1000 Participants Needed

Trial Summary

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.

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

Resmetirom is unique because it is an orally administered drug that specifically targets the liver and works by activating thyroid hormone receptor-β, which helps increase fat metabolism in the liver and reduce liver fat and inflammation. This mechanism is different from other treatments, as there are currently no approved drugs specifically for non-alcoholic steatohepatitis (NASH). ^{1 2 3 4 5}

What is the purpose of this trial?

This trial is studying the safety and tolerability of Resmetirom, a pill taken regularly. It involves patients who are already using this medication. Resmetirom helps manage certain health conditions by targeting specific parts of the body and has shown to reduce liver fat in patients with non-alcoholic steatohepatitis (NASH) in previous studies.

Research Team

Rebecca Taub, MD

Principal Investigator

Madrigal Pharmaceuticals, Inc.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

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 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]

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 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]

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. England pubmed.ncbi.nlm.nih.gov

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

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

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

5. 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]