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Resmetirom

Phase 3

Non-Alcoholic Fatty Liver Disease | Small molecule | Gastrointestinal |Madrigal Pharmaceuticals, Inc.|Last Updated: Jul 8, 2026

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Trial Design
RandomizedDouble-BlindCONTROLLEDDMC
Total Trials2
Total Enrollment2,153
FDA Designations
BREAKTHROUGH_THERAPYACCELERATED_APPROVALPRIORITY_REVIEW
Clinical trial landscape

Resmetirom · 5 trials · 5 indications

Phase 3 3Phase 2 1Phase 1 1
NCT05500222A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)NASH
ACTIVE NOT_RECRUITING845 Analytics
NCT04951219A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)Non-Alcoholic Fatty Liver Disease
ACTIVE NOT_RECRUITING810 Analytics
NCT04197479A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease PatientsNon-Alcoholic Fatty Liver Disease
COMPLETED1,343 Analytics
PHASE3ACTIVE NOT_RECRUITING
A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)
NASHUnlock trial analytics
PHASE3ACTIVE NOT_RECRUITING
A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Patients With Non-alcoholic Fatty Liver Disease (NAFLD), MAESTRO-NAFLD-Open-Label-Extension (MAESTRO-NAFLD-OLE)
Non-Alcoholic Fatty Liver DiseaseUnlock trial analytics
PHASE3COMPLETED
A Phase 3 Study to Evaluate Safety and Biomarkers of Resmetirom (MGL-3196) in Non Alcoholic Fatty Liver Disease Patients
Non-Alcoholic Fatty Liver DiseaseUnlock trial analytics
Study Endpoints
Primary Endpoints
Incidence Of adjudicated Composite Clinical Outcome event
Baseline up to Month 36

Any event of all-cause mortality, liver transplant, ascites, hepatic encephalopathy, gastroesophageal variceal hemorrhage, and confirmed increase of MELD score from \<12 to \>/= 15 due to liver disease

The effect of once daily, oral administration of resmetirom on the incidence of adverse events.
52 weeks
The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the incidence of adverse events.
52 weeks
Percent change from baseline in liver fat content (LFC) as assessed by MRI-PDFF at Week 28
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%.

Plasma pharmacokinetics - Cmax
8 days

Cmax after administration

Plasma pharmacokinetics - Tmax
8 days

Tmax after administration

Plasma pharmacokinetics - AUC(0-Last)
8 days

AUC(0-Last) after administration

Plasma pharmacokinetics - t1/2
8 days

t1/2 after administration

Secondary Endpoints
Percent change in the hepatic fat fraction as determined by MRI-PDFF from baseline
16 weeks
Percent change in LDL-C from baseline
28 weeks
The effect of once daily, oral administration of 80 or 100 mg resmetirom versus placebo on the percent change in low density lipoprotein C (LDL-C) from baseline to Week 24
24 weeks
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Study Design & Arms
AllocationRANDOMIZED
MaskingTRIPLE
ModelPARALLEL
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
ResmetiromACTIVE_COMPARATOR80 mg daily
PlaceboPLACEBO_COMPARATORmatching placebo daily
Double-blind 80 mg DailyEXPERIMENTALFor patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 80 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52
Double-blind 100 mg DailyEXPERIMENTALFor patients assigned to double-blind treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, double-blind resmetirom 100 mg for first 12 weeks followed by open-label resmetirom 100 mg for weeks 12-52
Open-labelEXPERIMENTALFor patients assigned to open-label treatment and who completed Week 52 and 56 of MAESTRO-NAFLD-1, open-label resmetirom at same dose as MGL-3196-14 for an additional 52 weeks. NASH cirrhosis patients may receive open-label resmetirom for up to an additional 66 months (ie, 52 weeks in MGL-3196-14 and up to 66 months in MGL-3196-18).
Open-Label 80 mgEXPERIMENTALFor patients with NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 80 mg for up to 66 months.
Open Label 100 mgEXPERIMENTALFor patients without NASH cirrhosis who were screen failures from MGL-3196-11, open-label resmetirom 100 mg for 52 weeks
Open-Label 40 mgEXPERIMENTALFor NASH cirrhosis patients who enter MGL-3196-18 directly or were screen failures from MGL-3196-19, open-label resmetirom 40 mg for up to 66 months.
Open label: resmetiromEXPERIMENTAL100 mg daily
Double blinded: matching placeboPLACEBO_COMPARATORPlacebo daily
Double blinded: resmetirom 80 mgEXPERIMENTAL80 mg daily
Double blinded: resmetirom 100 mgEXPERIMENTAL100 mg daily
Arm 1: Resmetirom 80 or 100 mg daily - Cohort 1ACTIVE_COMPARATOR -
Arm 2: Resmetirom 80 or 100 mg daily - Cohort 2ACTIVE_COMPARATOR -
Arm 3: Placebo - Cohort 1PLACEBO_COMPARATOR -
Arm 4: Placebo - Cohort 2PLACEBO_COMPARATOR -
Severe renal impairmentEXPERIMENTAL -
Normal Healthy MatchEXPERIMENTALMatched to severe renal impairment
Interventions
NameTypeDescription
ResmetiromDRUGRandomized 80 mg
PlaceboDRUGrandomized matching placebo
100 mg Resmetirom TabletDRUGOnce daily oral dose for 6 days
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Eligibility Criteria
Age Range18 Years to N/A
SexALL
Healthy VolunteersNo
Study Sites141

Inclusion Criteria: * A clinical diagnosis of NASH cirrhosis * At least 3 metabolic risk factors * Historical liver biopsy read as consistent with NASH cirrhosis. * Historical biopsy consistent with NASH with significant fibrosis, now with progression to cirrhosis. Or, no historical biopsy, with a ...

Countries:United StatesBelgiumCanadaFranceGermanyItalyPuerto RicoSpainUnited Kingdom
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Recent Changes (Last 90 Days)
LOWJul 8, 2026NCT05500222lastUpdatePostDate: changed
LOWJul 8, 2026NCT05500222lastUpdatePostDate: changed
LOWJun 16, 2026NCT07335601lastUpdatePostDate: changed
LOWJun 16, 2026NCT07335601lastUpdatePostDate: changed
LOWJun 16, 2026NCT07335601lastUpdatePostDate: changed
LOWJun 2, 2026NCT05500222Enrollment: 700 → 845
LOWJun 2, 2026NCT05500222Enrollment: 700 → 845
LOWJun 2, 2026NCT05500222Enrollment: 700 → 845
MEDIUMMay 29, 2026NCT07335601primaryCompletionDate: changed
MEDIUMMay 29, 2026NCT07335601primaryCompletionDate: changed
MEDIUMMay 29, 2026NCT07335601primaryCompletionDate: changed
MEDIUMMay 28, 2026NCT04951219Enrollment: 1000 → 810
MEDIUMMay 28, 2026NCT04951219Enrollment: 1000 → 810
LOWMay 26, 2026NCT07335601Status: ACTIVE_NOT_RECRUITING → RECRUITING
LOWMay 26, 2026NCT05500222primaryCompletionDate: changed
LOWMay 26, 2026NCT04951219primaryCompletionDate: changed
LOWMay 24, 2026NCT07335601studyFirstPostDate: changed
LOWMay 24, 2026NCT05500222studyFirstPostDate: changed
LOWMay 24, 2026NCT04951219studyFirstPostDate: changed