Study of Resmetirom in Children and Adolescents With MASH
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age6-17
SponsorMadrigal Pharmaceuticals, Inc.
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Male or female participants 6 to 17 years of age, inclusive.
Parent(s) or legal guardian(s) able to provide written informed consent (as required by local regulations), with participant assent obtained as applicable.
Diagnose of MASH with fibrosis stage F1-F3 based on a liver biopsy obtained within 24 months before Screening.
Hepatic fat fraction ≥8% by magnetic resonance imaging-proton density fat fraction (MRI-PDFF) obtained during the Screening period.
Disqualifiers
Previous exposure to resmetirom.
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.
Clinically significant thyroid disease or use of thyroid replacement therapy, triiodothyronine, thyroxine, or other prohibited thyroid medications.
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.
Trial design
Design model
Sequential
Treatments tested in this trial
Resmetirom
DrugResmetirom (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.
Treatment groups
61 Participants
are divided into 9 treatment groups9
Treatment groupsSee each treatment group below.
Group A: Adolescent Dose-Escalation Cohort 1Experimental treatment 1 intervention
Group B: Adolescent Dose-Escalation Cohort 2Experimental treatment 1 intervention
Group C: Adolescent Dose-Escalation Cohort 3Experimental treatment 1 intervention
Group D: Adolescent Dose-Escalation Cohort 4Experimental treatment 1 intervention
Group E: Adolescent Dose-Escalation Cohort 5Experimental treatment 1 intervention
Group F: Child Dose-Escalation Cohort 6Experimental treatment 1 intervention
Group G: Child Dose-Escalation Cohort 7Experimental treatment 1 intervention
Group H: Child Dose-Escalation Cohort 8Experimental treatment 1 intervention
Group I: Child Dose-Escalation Cohort 9Experimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
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.
Time frame
Baseline through approximately Day 21 (or the protocol-defined safety follow-up period)Secondary outcomes
1
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.
Time frame
Day 1 through Day 142
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.
Time frame
Baseline through Day 21Sponsors and contacts
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Source ClinicalTrials.gov