Resmetirom for post-liver transplant MASH with moderate to advanced fibrosis

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a randomized, double-blind, placebo-controlled Phase 2 trial enrolling two cohorts of adults at least 12 months after liver transplant: those with recurrent MASH after transplant for MASH cirrhosis and those with de novo MASH after transplant for other indications. Eligible participants must have hepatic steatosis ≥8% by MRI-PDFF and evidence of stage F2–F3 fibrosis by biopsy and/or noninvasive testing. Participants are randomized to resmetirom or placebo and followed with imaging, labs, and biopsy/noninvasive fibrosis assessments to measure changes in liver fat and fibrosis. The design focuses on safety and efficacy signals in the specific post-transplant population with metabolic risk factors.

Why it matters

Who can join: the full rules

Inclusion Criteria:

1. At least 12 months post-liver transplant at screening and meeting one of the following:

   * Cohort 1: Liver transplant for MASH cirrhosis with recurrent hepatic steatosis ≥8% by MRI-PDFF
   * Cohort 2: Liver transplant for non-MASH etiology with de novo hepatic steatosis ≥8% by MRI-PDFF
2. Presence of at least one metabolic risk factor, including overweight/obesity, dysglycemia or type 2 diabetes, hypertension or antihypertensive treatment, hypertriglyceridemia or low HDL cholesterol, or lipid-lowering therapy.
3. MASH with moderate to advanced liver fibrosis (F2-F3), confirmed by noninvasive fibrosis assessment (FibroScan and/or MRE) and a liver biopsy consistent with Stage F2/F3 MASH and no evidence of other liver pathology or graft rejection.
4. Stable renal function with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² prior to and during screening.
5. Stable liver enzymes at screening, without clinically significant worsening compared with recent historical values.
6. Stable immunosuppressive regimen for at least 3 months prior to screening.
7. Females of childbearing potential must have a negative pregnancy test, not be breastfeeding, and agree to use effective contraception during the study and for at least 30 days after the last dose; females not of childbearing potential are eligible.

Exclusion Criteria:

1. Participation in another interventional clinical trial with investigational drug exposure within 30 days (or 5 half-lives, whichever is longer) prior to screening.
2. Phosphatidylethanol (PEth) value of ≥20 ng/mL measured at screening or clinically significant alcohol use within 1 year prior to screening.
3. FibroScan VCTE \>20 kPa, a baseline biopsy demonstrating fibrosis consistent with F4, or MRE \> 5 kPa.
4. Uncontrolled or clinically significant thyroid disease, including active hyperthyroidism or untreated hypothyroidism.
5. Evidence of active liver disease other than MASH.
6. History of liver transplantation for an inborn error of metabolism.
7. Evidence of hepatic impairment or decompensation at screening.
8. Steroid resistant rejection of the transplanted liver or kidney, or a history of a rejection treated with high dose steroid within 3 months of screening.
9. Chronic rejection or chronic plasma-cell hepatitis.
10. Significant post-transplant vascular or biliary complications.
11. Significant cardiovascular or cerebrovascular disease within 6 months prior to randomization.
12. Uncontrolled hypertension at screening or randomization.
13. Current hepatocellular carcinoma.
14. Known human immunodeficiency virus (HIV) infection or other clinically significant immunocompromised state.
15. Any serious medical condition with a life expectancy of less than 5 years.
16. Current substance abuse or drug addiction.
17. Significant psychiatric, cognitive, or social conditions that would interfere with study participation or compliance, in the Investigator's judgment.
18. Known hypersensitivity to study drug or any of its excipients.
19. Use of prohibited concomitant medications that may affect liver function, steatosis, thyroid function, or study outcomes, or unstable doses of allowed metabolic therapies prior to randomization.
20. Use of statins above protocol-allowed doses or unstable lipid-lowering therapy prior to randomization.
21. Contraindications to MRI, including implanted devices incompatible with MRI, severe claustrophobia, or inability to undergo MRI procedures.

Where it's running

• University of California San Diego
  La Jolla, California, United States Recruiting
• University of California, San Francisco
  San Francisco, California, United States Recruiting
• University of Colorado
  Aurora, Colorado, United States Recruiting
• Northwestern University
  Chicago, Illinois, United States Recruiting
• Mayo Clinic
  Rochester, Minnesota, United States Recruiting
• Northwell Health Inc, Center for Liver Disease and Transplantation
  Manhasset, New York, United States Recruiting

Study contacts

• Study coordinator: David Hernandez, MD
• Email: dhernandez@madrigalpharma.com
• Phone: 302-640-2217

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.