Resmetirom for NASH Cirrhosis

Recruiting in Palo Alto (17 mi)

+54 other locations

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Madrigal Pharmaceuticals, Inc.

Disqualifiers: Chronic liver diseases, MELD score ≥12, others

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

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.

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 trial coordinators or your doctor.

What data supports the effectiveness of the drug Resmetirom for NASH Cirrhosis?

Research shows that Resmetirom, a drug targeting liver cells, can reduce liver fat and improve liver health in patients with non-alcoholic steatohepatitis (NASH), a condition similar to NASH cirrhosis. It has been shown to decrease liver fat, improve cholesterol levels, and reduce liver stiffness, indicating its potential effectiveness for liver-related conditions. ^{1 2 3 4 5}

What makes the drug Resmetirom unique for treating NASH cirrhosis?

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 and reduce liver fat and inflammation. This targeted approach is different from other treatments that may not focus specifically on the liver or use this mechanism. ^{1 2 3 4 5}

Research Team

Thomas Hare

Principal Investigator

VP, Clinical Research

Eligibility Criteria

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.

Inclusion Criteria

Enhanced liver function (ELF) ≥9.8, only if MRE is unavailable or contraindicated.

My latest liver biopsy shows significant damage and fat.

I have a history of NASH with significant fibrosis, now with cirrhosis.

Exclusion Criteria

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

I have never had liver failure or serious liver problems.

Participants with MELD score ≥12 due to liver disease are excluded.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

8 weeks

Treatment

Participants receive 80 mg resmetirom or matching placebo daily until the required number of Composite Clinical Outcome events are achieved

Approximately 3 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Other)
• Resmetirom (Thyroid Hormone Receptor Agonist)

Trial Overview 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.

Participant Groups

Group I: Resmetirom Active Control 1 Intervention

80 mg daily

Group II: Placebo Placebo Group 2 Interventions

matching 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]

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 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. Switzerland pubmed.ncbi.nlm.nih.gov

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

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

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