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

Phase 2, Randomized, Double-Blind, Placebo-Controlled Study to Evaluate MGL-3196 (Resmetirom) in Patients With MASH Who Have Undergone Liver Transplant for MASH Cirrhosis or Other Etiologies

This trial will test resmetirom versus placebo to see if it reduces liver fat and improves fibrosis in people who developed MASH after a liver transplant.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years to 75 Years
• Sex: All
• Sponsor: Madrigal Pharmaceuticals, Inc. (industry)
• Locations: 15 sites (La Jolla, California and 14 other locations)
• Trial ID: NCT07335601 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults at least 12 months after liver transplant with MRI-PDFF ≥8%, biopsy- or noninvasive-confirmed MASH with F2–F3 fibrosis, at least one metabolic risk factor, and stable renal and liver function.

Not a fit: Patients with F0–F1 or F4 cirrhosis, active graft rejection or other non-MASH liver disease, unstable organ function, or eGFR <30 mL/min/1.73 m² are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, resmetirom could lower liver fat and slow or reverse fibrosis in post-transplant MASH patients, potentially preserving graft health and improving long-term outcomes.

How similar studies have performed: Resmetirom has shown reductions in liver fat and some histologic improvement in non-transplant NASH trials, but its use in post-transplant MASH is novel.

Eligibility criteria

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 4 weeks 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 30 days after the last dose; females not of childbearing potential are eligible.
8. Sexually active males with partners of childbearing potential must agree to use effective contraception during the study and for 30 days after the last dose and not donate sperm during this period.

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 this trial is running

La Jolla, California and 14 other locations

• University of California San Diego — La Jolla, California, United States (NOT_YET_RECRUITING)
• University of California Los Angeles Medical Center — Los Angeles, California, United States (NOT_YET_RECRUITING)
• University of California, San Francisco — San Francisco, California, United States (NOT_YET_RECRUITING)
• University of Colorado — Aurora, Colorado, United States (NOT_YET_RECRUITING)
• Northwestern University — Chicago, Illinois, United States (RECRUITING)
• The University of Chicago Medicine — Chicago, Illinois, United States (NOT_YET_RECRUITING)
• Mayo Clinic — Rochester, Minnesota, United States (NOT_YET_RECRUITING)
• Northwell Health Inc, Center for Liver Disease and Transplantation — Manhasset, New York, United States (NOT_YET_RECRUITING)
• New York Presbyterian Hospital — New York, New York, United States (NOT_YET_RECRUITING)
• Vanderbilt University Medical Center (VUMC) — Nashville, Tennessee, United States (NOT_YET_RECRUITING)
• Dallas Methodist — Dallas, Texas, United States (NOT_YET_RECRUITING)
• Houston Methodist Hospital — Houston, Texas, United States (NOT_YET_RECRUITING)
• Intermountain Medical Center — Murray, Utah, United States (NOT_YET_RECRUITING)
• University of Virginia Health System — Charlottesville, Virginia, United States (NOT_YET_RECRUITING)
• University Health Network - Toronto General Hospital (TGH) — Toronto, Ontario, Canada (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: David Hernandez, MD

Conditions: MASH - Metabolic Dysfunction-Associated Steatohepatitis, Post-Liver Transplant, Cirrhosis, Metabolic dysfunction-associated steatohepatitis, MASLD, MASH, Liver