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

NCT07335601 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: MGL-3196-27
• Study Type: interventional
• Target: 120
• Locations: 2 countries
• Sites: 15

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

Keywords

Post-Liver Transplant; Cirrhosis; Metabolic dysfunction-associated steatohepatitis (MASH); MASLD; MASH; Liver

Outcome Measures

Primary Outcomes (1)

• Percent change from baseline in liver fat content (LFC) as assessed by MRI-PDFF at Week 28

  To determine the effect of MGL-3196/Resmetirom versus matching placebo on percent change from Baseline to Week 28 in hepatic fat fraction by magnetic resonance imaging proton density fat fraction (MRI-PDFF) in patients with baseline MRI-PDFF ≥8%.

  28 weeks

Secondary Outcomes (4)

• To evaluate the safety and tolerability of once-daily, oral administration of MGL-3196/resmetirom versus matching placebo in patients who have undergone a liver transplant

  52 weeks

• 1.To determine the effect of MGL-3196/resmetirom versus matching placebo on liver stiffness as measured by FibroScan vibration controlled transient elastography (VCTE; kPa)

  28 and 52 Weeks

• 2. To determine the effect of MGL-3196/resmetirom versus matching placebo on serum lipid parameters

  28 and 52 Weeks

• 3. To determine the effect of MGL-3196/resmetirom versus matching placebo on liver biochemistries

  28 and 52 weeks

Study Arms (4)

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

ACTIVE COMPARATOR

Drug: Resmetirom

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

ACTIVE COMPARATOR

Drug: Resmetirom

Arm 3: Placebo - Cohort 1

PLACEBO COMPARATOR

Drug: Placebo

Arm 4: Placebo - Cohort 2

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Resmetirom DRUG

Randomized 80 or 100 mg

Arm 1: Resmetirom 80 or 100 mg daily - Cohort 1; Arm 2: Resmetirom 80 or 100 mg daily - Cohort 2

Placebo DRUG

Placebo

Arm 3: Placebo - Cohort 1; Arm 4: Placebo - Cohort 2

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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.
• 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.
• Stable renal function with estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² prior to and during screening.
• Stable liver enzymes at screening, without clinically significant worsening compared with recent historical values.
• Stable immunosuppressive regimen for at least 4 weeks prior to screening.
• 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.
• 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.

You may not qualify if:

• Participation in another interventional clinical trial with investigational drug exposure within 30 days (or 5 half-lives, whichever is longer) prior to screening.
• Phosphatidylethanol (PEth) value of ≥20 ng/mL measured at screening or clinically significant alcohol use within 1 year prior to screening.
• FibroScan VCTE \>20 kPa, a baseline biopsy demonstrating fibrosis consistent with F4, or MRE \> 5 kPa.
• Uncontrolled or clinically significant thyroid disease, including active hyperthyroidism or untreated hypothyroidism.
• Evidence of active liver disease other than MASH.
• History of liver transplantation for an inborn error of metabolism.
• Evidence of hepatic impairment or decompensation at screening.
• 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.
• Chronic rejection or chronic plasma-cell hepatitis.
• Significant post-transplant vascular or biliary complications.
• Significant cardiovascular or cerebrovascular disease within 6 months prior to randomization.
• Uncontrolled hypertension at screening or randomization.
• Current hepatocellular carcinoma.
• Known human immunodeficiency virus (HIV) infection or other clinically significant immunocompromised state.
• Any serious medical condition with a life expectancy of less than 5 years.

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

Study Sites (15)

University of California San Diego

La Jolla, California, 92037, United States

NOT YET RECRUITING

University of California Los Angeles Medical Center

Los Angeles, California, 90095, United States

NOT YET RECRUITING

University of California, San Francisco

San Francisco, California, 94143, United States

NOT YET RECRUITING

University of Colorado

Aurora, Colorado, 80045, United States

NOT YET RECRUITING

Northwestern University

Chicago, Illinois, 60208, United States

RECRUITING

The University of Chicago Medicine

Chicago, Illinois, 60637, United States

NOT YET RECRUITING

Mayo Clinic

Rochester, Minnesota, 55905, United States

NOT YET RECRUITING

Northwell Health Inc, Center for Liver Disease and Transplantation

Manhasset, New York, 11030, United States

NOT YET RECRUITING

New York Presbyterian Hospital

New York, New York, 10065, United States

NOT YET RECRUITING

Vanderbilt University Medical Center (VUMC)

Nashville, Tennessee, 37212, United States

NOT YET RECRUITING

Dallas Methodist

Dallas, Texas, 75203, United States

NOT YET RECRUITING

Houston Methodist Hospital

Houston, Texas, 77030, United States

NOT YET RECRUITING

Intermountain Medical Center

Murray, Utah, 84107, United States

NOT YET RECRUITING

University of Virginia Health System

Charlottesville, Virginia, 22903, United States

NOT YET RECRUITING

University Health Network - Toronto General Hospital (TGH)

Toronto, Ontario, M5G 2C4, Canada

NOT YET RECRUITING

MeSH Terms

Conditions

Fibrosis

Interventions

resmetirom

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Tom Hare, MS

  Madrigal Pharmaceuticals, Inc.

  STUDY DIRECTOR

Central Study Contacts

David Hernandez, MD

CONTACT

302-640-2217; dhernandez@madrigalpharma.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Randomized matching placebo

Study Record Dates

• First Submitted: January 7, 2026
• First Posted: January 13, 2026
• Study Start: December 29, 2025
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: April 30, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (14); CA (1)