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A Phase 3 Study to Evaluate the Effect of Resmetirom on Clinical Outcomes in Patients With Well-compensated NASH Cirrhosis (MAESTRO-NASH-OUTCOMES)

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ClinicalTrials.gov Identifier: NCT05500222
Recruitment Status : Recruiting
First Posted : August 15, 2022
Last Update Posted : March 25, 2024
Sponsor:
Information provided by (Responsible Party):
Madrigal Pharmaceuticals, Inc.

Brief Summary:
This study will determine the effect of oral 80 mg resmetirom administered once daily on participants with well-compensated non-alcoholic steatohepatitis (NASH) cirrhosis by measuring the time to experiencing a Composite Clinical Outcome event.

Condition or disease Intervention/treatment Phase
NASH Cirrhosis, Liver Drug: Resmetirom Drug: Placebo Phase 3

Detailed Description:
This is a multi-national, multicenter, double-blind, randomized, placebo-controlled study in participants with well-compensated NASH cirrhosis. Participants will be randomized 3:1 in a blinded manner to receive 80 mg resmetirom or matching placebo given orally once daily in the morning for the duration of the study (until the required number of Composite Clinical Outcome events are achieved). Composite Clinical Outcome events are defined as any of the following: liver-related and CV mortality, liver transplant, and significant hepatic events, including potential hepatic decompensation events (ascites, hepatic encephalopathy, or gastroesophageal variceal hemorrhage), and confirmed increase of Model for End-stage Liver Disease (MELD) score from <12 to ≥15. The study comprises an up to 60-day screening period and an approximately 3-year treatment period.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 700 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Effect of Resmetirom on Liver-related Outcomes in Patients With Well-compensated (Child-Pugh A) Non-alcoholic Steatohepatitis (NASH) Cirrhosis (MAESTRO-NASH-OUTCOMES)
Actual Study Start Date : August 26, 2022
Estimated Primary Completion Date : December 2026
Estimated Study Completion Date : January 2027

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Resmetirom
80 mg daily
Drug: Resmetirom
Randomized 80 mg
Other Name: MGL-3196

Placebo Comparator: Placebo
matching placebo daily
Drug: Placebo
randomized matching placebo




Primary Outcome Measures :
  1. Incidence Of adjudicated Composite Clinical Outcome event [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Definitive (by histologic documentation) or probable NASH as causative agent for cirrhosis, following a modified version of the NASH Cirrhosis: Liver Forum Consensus Definitions for Clinical Trials.
  • a. Most recent biopsy (within last 5 years) shows cirrhosis with a NAS of ≥ 2, and at least two components: one being steatosis and at least one other component; OR NAS of ≥ 2, if steatosis = 0 or is ungraded with inflammation and/or ballooning, eligible with an MRI-PDFF >5%. If steatosis and ballooning and/or steatosis and inflammation are noted by the local pathologist, then the biopsy qualifies even if a NAS is not provided (Approximately 70% of the study patient population) b. Historical biopsy (within last 5 years) showed NASH with significant fibrosis with pathology report documenting "F2" or "F3", with at least steatosis either by biopsy with no minimal percentage required or by MRI-PDFF >5%, AND inflammation or ballooning. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (see Appendix 7) (Up to approximately 20% of study patient population) c. Historical biopsy (within last 5 years) shows steatosis. Pathology report documents steatosis with no minimal percentage required. Now with cirrhosis, either by clinical history or current features, imaging, noninvasive tests, or biopsy (see Appendix 7). Prescreening metabolic risk factors must include obesity and/or T2D. (Up to approximately 10% of study patient population.)
  • Well-compensated NASH cirrhosis at screening and baseline with Child-Pugh A (score of 5-6) (no history of hepatic decompensation event).
  • At least 3 metabolic risk factors
  • Magnetic Resonance Imaging Proton Density Fat Fraction (MRI-PDFF) that is obtained during the Screening period or a historic MRI-PDFF at ≤8 weeks old at the time of randomization with no weight change ≥5% weight change in that interval.
  • MRE ≥4.2 where MRE is available.
  • Enhanced liver function (ELF) ≥9.8, only if MRE is unavailable or contraindicated.

Exclusion Criteria:

  • Participants with a chronic liver diseases other than NASH cirrhosis, such as primary biliary cholangitis, primary sclerosing cholangitis, Hepatitis B positive, Hepatitis C, history or evidence of current active autoimmune hepatitis, history or evidence of Wilson's disease, history or evidence of alpha-1-antitrypsin deficiency, history or evidence of genetic hemochromatosis (hereditary, primary), evidence of drug-induced liver disease, as defined on the basis of typical exposure and history, known bile duct obstruction, or suspected or confirmed liver cancer, are excluded.
  • Participants with MELD score ≥12 due to liver disease are excluded.
  • Participants with a history of hepatic decompensation or impairment are excluded.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05500222


Contacts
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Contact: Thomas Hare 267-520-0252 info@madrigalpharma.com

Locations
Show Show 55 study locations
Sponsors and Collaborators
Madrigal Pharmaceuticals, Inc.
Investigators
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Study Director: Thomas Hare VP, Clinical Research
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Responsible Party: Madrigal Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT05500222    
Other Study ID Numbers: MGL-3196-19
First Posted: August 15, 2022    Key Record Dates
Last Update Posted: March 25, 2024
Last Verified: March 2024
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Liver Cirrhosis
Fibrosis
Pathologic Processes
Liver Diseases
Digestive System Diseases