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

Official title

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

Overview

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.

Interventions

• Drug Resmetirom
  Randomized 80 or 100 mg
• Drug Placebo
  Placebo

Primary outcome measures

• Percent change from baseline in liver fat content (LFC) as assessed by MRI-PDFF at Week 28 [Time frame: 28 weeks]

Secondary outcome measures (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 [Time frame: 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) [Time frame: 28 and 52 Weeks]
• 2. To determine the effect of MGL-3196/resmetirom versus matching placebo on serum lipid parameters [Time frame: 28 and 52 Weeks]
• 3. To determine the effect of MGL-3196/resmetirom versus matching placebo on liver biochemistries [Time frame: 28 and 52 weeks]

Eligibility criteria

Inclusion criteria

• 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 3 months 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 at least 30 days after the last dose; females not of childbearing potential are eligible.

Exclusion criteria

• 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.
• Current substance abuse or drug addiction.
• Significant psychiatric, cognitive, or social conditions that would interfere with study participation or compliance, in the Investigator's judgment.
• Known hypersensitivity to study drug or any of its excipients.
• 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.
• Use of statins above protocol-allowed doses or unstable lipid-lowering therapy prior to randomization.
• Contraindications to MRI, including implanted devices incompatible with MRI, severe claustrophobia, or inability to undergo MRI procedures.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Triple blind

Primary purpose

Treatment

Study locations

United States · 16 centers

• University of California San Diego — La Jolla
• University of California Los Angeles Medical Center — Los Angeles
• University of California, San Francisco — San Francisco
• University of Colorado — Aurora
• Medstar Georgetown University Hospital — Washington D.C.
• Northwestern University — Chicago
• The University of Chicago Medicine — Chicago
• Mayo Clinic — Rochester
• … and 8 more centers

Canada · 1 center

• University Health Network - Toronto General Hospital (TGH) — Toronto

Identifiers

NCT: NCT07335601 · MGL-3196-27

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗