Resmetirom for NASH Cirrhosis

Recruiting at 54 trial locations

Overseen By Thomas Hare

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Madrigal Pharmaceuticals, Inc.

Disqualifiers: Chronic liver diseases, MELD score ≥12, 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

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

Compensation: Varies

Number of Visits: Unknown

Duration: Approximately 3 years

700 Participants Needed

What You Need to Know Before You Apply

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 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}

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}

Who Is on the Research Team?

Thomas Hare

Principal Investigator

VP, Clinical Research

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Resmetirom

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.

How Is the Trial Designed?

Group I: Resmetirom Active Control 1 Intervention

80 mg daily

Group II: Placebo Placebo Group 2 Interventions

matching placebo daily

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]

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]

Citations

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]