Resmetirom for NASH Cirrhosis

Not currently recruiting at 55 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called resmetirom to determine its effectiveness for individuals with non-alcoholic steatohepatitis (NASH) cirrhosis. Researchers aim to discover if taking 80 mg of resmetirom daily can improve participants' health by delaying serious liver-related events. Participants will receive either the actual medication or a placebo (a pill with no active medicine) to compare results. This trial may suit those diagnosed with NASH cirrhosis who have not experienced liver failure events and have certain metabolic issues like obesity or type 2 diabetes. As a Phase 3 trial, this study represents the final step before potential FDA approval, offering participants a chance to contribute to a treatment that could soon become widely available.

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.

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

Research has shown that resmetirom has been tested for safety in people with non-alcoholic steatohepatitis (NASH) and liver scarring. In these studies, most participants tolerated resmetirom well. Many did not experience worsening liver scarring, and some even saw improvements.

Safety information indicates that resmetirom did not cause serious side effects for most participants. This treatment has been tested in advanced studies, providing a higher level of confidence in its safety for humans. It is important to consult a healthcare provider to determine if joining a trial is appropriate. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for NASH?

Resmetirom is unique because it specifically targets thyroid hormone receptor beta to reduce liver fat and inflammation in NASH cirrhosis patients. Unlike standard treatments that primarily focus on managing symptoms or controlling risk factors like diabetes and obesity, Resmetirom directly addresses the underlying liver condition. This targeted approach has the potential to halt or even reverse liver damage, which is why researchers are excited about its promise for improving patient outcomes.

What evidence suggests that resmetirom might be an effective treatment for NASH cirrhosis?

Research has shown that resmetirom, which participants in this trial may receive, effectively treats non-alcoholic steatohepatitis (NASH), even in cases with liver scarring (fibrosis). Studies indicate that both the 80-mg and 100-mg doses of resmetirom outperform a placebo in resolving NASH and improving liver health. Resmetirom activates thyroid hormone receptors, reducing liver fat. In one study, a reduction in liver fat by at least 30% correlated with a 37% rate of NASH resolution. These findings suggest that resmetirom could be promising for people with NASH cirrhosis. ^{1 2 3 6 7}

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]

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 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]

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. jmcp.org jmcp.org/doi/full/10.18553/jmcp.2023.29.10.1169

Resmetirom for nonalcoholic steatohepatitis Resmetirom is a once-daily oral drug being investigated for the treatment of NASH with fibrosis. It is a thyroid hormone receptor β agonist that acts by ...

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

A Phase 3, Randomized, Controlled Trial of Resmetirom in ... Both the 80-mg dose and the 100-mg dose of resmetirom were superior to placebo with respect to NASH resolution and improvement in liver ...

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. ir.madrigalpharma.com ir.madrigalpharma.com/news-releases/news-release-details/madrigal-announces-new-clinical-data-demonstrating-rezdiffratm

Madrigal Announces New Clinical Data Demonstrating ... A positive outcome is expected to support the full approval of Rezdiffra for noncirrhotic MASH and expand the eligible patient population for ...

5. 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 ...

6. nejm.org nejm.org/doi/10.1056/NEJMoa2309000

A Phase 3, Randomized, Controlled Trial of Resmetirom in ... NASH resolution with no worsening of fibrosis was achieved in 25.9% of the patients in the 80-mg resmetirom group and 29.9% of those in the 100- ...

7. ir.madrigalpharma.com ir.madrigalpharma.com/news-releases/news-release-details/madrigal-pharmaceuticals-completes-enrollment-clinical-outcomes

Madrigal Pharmaceuticals Completes Enrollment of ... Positive results from the MAESTRO-NASH OUTCOMES study could make resmetirom the first medication approved for patients with compensated NASH ...