Study to Evaluate Resmetirom in Post-Liver Transplant Patients With MASH

NCT ID: NCT07335601

Last Updated: 2026-01-13

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-12-29
• Study Completion Date: 2027-12-31

Brief Summary

A Phase 2 double-blind, randomized, placebo-controlled study to evaluate resmetirom in 2 cohorts of subjects with moderate to advanced fibrosis, consistent with stage F2 and F3 fibrosis, who have undergone liver transplant. Cohort 1 will consist of patients who have undergone liver transplant for MASH cirrhosis who developed recurrent MASH. Cohort 2 will consist of subjects who have undergone liver transplant for indications other than MASH cirrhosis who developed de novo MASH.

Conditions

MASH - Metabolic Dysfunction-Associated Steatohepatitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Arm 1: Resmetirom 80 or 100 mg daily - Cohort 1

Group Type: ACTIVE_COMPARATOR

Resmetirom

Intervention Type: DRUG

Randomized 80 or 100 mg

Arm 2: Resmetirom 80 or 100 mg daily - Cohort 2

Group Type: ACTIVE_COMPARATOR

Resmetirom

Intervention Type: DRUG

Randomized 80 or 100 mg

Arm 3: Placebo - Cohort 1

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Arm 4: Placebo - Cohort 2

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo

Interventions

Resmetirom

Randomized 80 or 100 mg

Intervention Type: DRUG

Placebo

Placebo

Intervention Type: DRUG

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Madrigal Pharmaceuticals, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Tom Hare, MS

Role: STUDY_DIRECTOR

Madrigal Pharmaceuticals, Inc.

Locations

University of California San Diego

La Jolla, California, United States

University of California Los Angeles Medical Center

Los Angeles, California, United States

University of California, San Francisco

San Francisco, California, United States

University of Colorado

Aurora, Colorado, United States

Northwestern University

Chicago, Illinois, United States

The University of Chicago Medicine

Chicago, Illinois, United States

Mayo Clinic

Rochester, Minnesota, United States

Northwell Health Inc, Center for Liver Disease and Transplantation

Manhasset, New York, United States

New York Presbyterian Hospital

New York, New York, United States

Vanderbilt University Medical Center (VUMC)

Nashville, Tennessee, United States

Dallas Methodist

Dallas, Texas, United States

Houston Methodist Hospital

Houston, Texas, United States

Intermountain Medical Center

Murray, Utah, United States

University of Virginia Health System

Charlottesville, Virginia, United States

University Health Network - Toronto General Hospital (TGH)

Toronto, Ontario, Canada

Countries

United States; Canada

Other Identifiers

MGL-3196-27

Identifier Type: -

Identifier Source: org_study_id