NCT07335601RecruitingPhase 2
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
Madrigal Pharmaceuticals, Inc.19 sites in 2 countries120 target enrollmentStarted: December 29, 2025Last updated:
Interventions
Drugs
Trial Snapshot
- Phase
- Phase 2
- Status
- Recruiting
- Enrollment
- 120
- Locations
- 19
- Primary Endpoint
- Percent change from baseline in liver fat content (LFC) as assessed by MRI-PDFF at Week 28
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Arm 3: Placebo - Cohort 1
Placebo Comparator
Intervention: Placebo (Drug)
Arm 2: Resmetirom 80 or 100 mg daily - Cohort 2
Active Comparator
Intervention: Resmetirom (Drug)
Arm 4: Placebo - Cohort 2
Placebo Comparator
Intervention: Placebo (Drug)
Arm 1: Resmetirom 80 or 100 mg daily - Cohort 1
Active Comparator
Intervention: Resmetirom (Drug)
Outcomes
Primary Outcomes
Percent change from baseline in liver fat content (LFC) as assessed by MRI-PDFF at Week 28
Time Frame: 28 weeks
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%.
Secondary Outcomes
- 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)
Investigators
Study Sites (19)
Loading locations...
Similar Trials
Withdrawn
Phase 1
Phase I, double-blind, randomized, placebo-controlled study investigating the safety, tolerability and concentrations of the study product KAND145 in healthy volunteersOvarian cancer2023-503909-11-00Kancera AB80
Active, not recruiting
Phase 2
A Study to Evaluate the Efficacy, Safety, and Tolerability of ASC30 Tablets in Participants With Type 2 Diabetes MellitusNCT07321678Ascletis Pharma (China) Co., Limited100
Recruiting
Phase 2
A Study of SRSD107 in Participants With Chronic Coronary and/or Peripheral Arterial DiseasePeripheral Arterial DiseaseNCT07318155Sirius Therapeutics Co., Ltd.104
Terminated
Phase 2
A Clinical Trial of TQH2929 Injection in Patients With Acute Flare-up of Generalized Pustular PsoriasisGeneralized Pustular PsoriasisNCT07314060Chia Tai Tianqing Pharmaceutical Group Co., Ltd.36
Recruiting
Phase 3
Study of Oral Deucrictibant XR Tablet for Prophylaxis and Deucrictibant IR Capsule for On-Demand Treatment of Angioedema Attacks in Adults With Acquired Angioedema Due to C1 Inhibitor DeficiencyNCT07266805Pharvaris Netherlands B.V.32