Study of Resmetirom in Children and Adolescents With MASH

A Phase 2a, Multicenter, Open-label, Multiple Ascending Dose Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of Resmetirom in Pediatric Subjects Ages 6-17 Years With MASH With Fibrosis Stage F1-F3

This study will evaluate the safety, pharmacokinetics (how the body absorbs, distributes, metabolizes, and eliminates the drug), and pharmacodynamics (how the drug affects the body) of resmetirom in children and adolescents with metabolic dysfunction-associated steatohepatitis (MASH) and liver fibrosis. Participants will receive oral resmetirom once daily for approximately 14 days at one of several dose levels. The information from this study will help determine appropriate dosing and further evaluate the safety and biological effects of resmetirom in pediatric participants with MASH.

Study Overview

• Status: Recruiting
• Conditions: MASH; MASH - Metabolic Dysfunction-Associated Steatohepatitis
• Intervention / Treatment: Drug: Resmetirom

• Study Type: Interventional
• Enrollment (Estimated): 61
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Tom Hare; Phone Number: 267-406-0611; Email: info@madrigalpharma.com

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46402
      • Recruiting
      • Riley Hospital for Children at IU Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female participants 6 to 17 years of age, inclusive.
2. Parent(s) or legal guardian(s) able to provide written informed consent (as required by local regulations), with participant assent obtained as applicable.
3. Diagnose of MASH with fibrosis stage F1-F3 based on a liver biopsy obtained within 24 months before Screening.
4. Hepatic fat fraction ≥8% by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) obtained during the Screening period.
5. Able to swallow study tablets.
6. Females of childbearing potential must have a negative pregnancy test at screening, must not be pregnant or breastfeeding, and must agree to use a highly effective method of contraception during the study and for at least 30 days after the last dose of study drug. Premenarchal participants and those not of childbearing potential are eligible without contraception.

Exclusion Criteria:

1. Previous exposure to resmetirom.
2. Clinically significant liver disease other than MASH or evidence of cirrhosis (F4), decompensated liver disease, or other hepatic conditions that may interfere with study participation or interpretation of results.
3. Clinically significant thyroid disease or use of thyroid replacement therapy, triiodothyronine, thyroxine, or other prohibited thyroid medications.
4. Use of prohibited concomitant medications, including medications known to affect hepatic steatosis or liver function, lipid-lowering therapies, CYP2C8 inhibitors, OATP1B1/OATP1B3/BCRP inhibitors, protease inhibitors, St. John's Wort, or other medications prohibited by the protocol.
5. Use of glucagon-like peptide-1 (GLP-1) receptor agonists unless on a stable dose for at least 24 weeks before screening.
6. Clinically significant alcohol or substance abuse, or regular use of tobacco/nicotine products within 6 months before screening.
7. Active or clinically significant infection, including chronic hepatitis B or hepatitis C infection, HIV infection, or other immunocompromising conditions.
8. History or presence of clinically significant cardiovascular, pulmonary, renal, gastrointestinal, neurologic, hematologic, endocrine, psychiatric, or other medical conditions that, in the opinion of the Investigator, could interfere with study participation or interpretation of study results.
9. History of malignancy within the past 5 years (except adequately treated non-melanoma skin cancer or other protocol-permitted exceptions).
10. History of organ transplantation or known immunocompromised status.
11. Participation in another investigational study within 60 days or 5 half-lives (whichever is longer) before screening, unless permitted by the protocol.
12. Major surgery within 6 weeks before screening.
13. Known hypersensitivity to resmetirom or any excipient.
14. Females who are pregnant or breastfeeding.
15. Any condition that, in the opinion of the Investigator, would compromise participant safety, compliance, or the integrity of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

9

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Adolescent Dose-Escalation Cohort 1; Adolescents participants 12 to 17 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Adolescent Dose-Escalation Cohort 2; Adolescent participants 12 to 17 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Adolescent Dose-Escalation Cohort 3; Adolescent participants 12 to 17 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Adolescent Dose-Escalation Cohort 4; Adolescent participants 12 to 17 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Adolescent Dose-Escalation Cohort 5; Adolescent participants 12 to 17 years of age receive the fifth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Child Dose-Escalation Cohort 6; Children participants 6 to 11 years of age receive the first planned dose level of oral resmetirom once daily for approximately 14 days.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Child Dose-Escalation Cohort 7; Children participants 6 to 11 years of age receive the second planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Child Dose-Escalation Cohort 8; Children participants 6 to 11 years of age receive the third planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.
Experimental: Child Dose-Escalation Cohort 9; Children participants 6 to 11 years of age receive the fourth planned dose level of oral resmetirom once daily for approximately 14 days following review of safety and PK data.	Drug: Resmetirom; Resmetirom (MGL-3196) : Oral resmetirom administered once daily. Participants receive one of several protocol-defined dose levels assigned according to the sequential multiple ascending-dose study design. Dose escalation proceeds following review of available safety, pharmacokinetic, and pharmacodynamic data.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and tolerability of multiple ascending doses of resmetirom	Safety and tolerability will be assessed by the incidence and severity of adverse events, serious adverse events, clinical laboratory evaluations, vital signs, 12-lead electrocardiograms, physical examinations, and other protocol-defined safety assessments.	Baseline through approximately Day 21 (or the protocol-defined safety follow-up period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacokinetic parameters of resmetirom (MGL-3196) and its metabolite (MGL-3623)	Pharmacokinetic parameters of resmetirom and MGL-3623 following single and repeated dosing, including CL/F (parent only), Vz/F (parent only), Cmax, AUC0-24, and AUC0-∞ after the first dose, and CL/F (parent only), Cmax, and AUC0-24 following repeated dosing, as applicable.	Day 1 through Day 14
Pharmacodynamic biomarkers associated with resmetirom exposure	Changes in pharmacodynamic biomarkers, including thyroid axis markers, sex hormone-binding globulin, and lipid parameters and their relationship to dose and/or plasma concentrations of resmetirom.	Baseline through Day 21

Collaborators and Investigators

• Sponsor: Madrigal Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2026
• Primary Completion (Estimated): July 1, 2029
• Study Completion (Estimated): July 1, 2029

Study Registration Dates

• First Submitted: August 10, 2026
• First Submitted That Met QC Criteria: August 10, 2026
• First Posted (Actual): August 13, 2026

Study Record Updates

• Last Update Posted (Actual): September 11, 2026
• Last Update Submitted That Met QC Criteria: September 10, 2026
• Last Verified: September 1, 2026

More Information

Terms related to this study

• Keywords: Fibrosis; Pediatric; Liver Disease; Resmetirom; MASLD; MASH
• Additional Relevant MeSH Terms: Pathologic Processes; Digestive System Diseases; Pathological Conditions, Signs and Symptoms; Fibrosis; Liver Diseases; resmetirom
• Other Study ID Numbers: MGL-3196-29

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No