Madrigal Pharmaceuticals is conducting a Phase 3 clinical research study, MAESTRO-NASH designed to examine the effect of the investigational drug resmetirom (also known as MGL-3196) in patients with fatty liver disease, more specifically patients with Nonalcoholic Steatohepatitis (NASH), and evidence of liver scarring, or liver fibrosis.
Fatty liver diseases or non-alcoholic fatty liver disease (NAFLD) is a common liver disease characterized by a buildup of fat in the liver. NAFLD tends to develop in people who are overweight or obese or have diabetes, high cholesterol or high triglycerides. NAFLD affects up to 25% of people in the United States.
Typically 3-5%, and in some studies up to 12%, of patients with a fatty liver may progress to a more serious form of fatty liver called, non-alcoholic steatohepatitis (NASH). NASH is a liver disease that is associated with an increased amount of inflammation in the liver. NASH can lead to a buildup of scar tissue in the liver called cirrhosis and increase the chances of getting heart disease. About 25% of NASH patients may develop liver-related disease or death. Frequently, the earliest forms of NAFLD and even NASH have no symptoms, and people can have NASH for years before symptoms occur. No therapies have been approved for the treatment of NASH. For more information see American Liver Foundation article on NAFLD and NASH.
Resmetirom works by interacting with a form of thyroid hormone receptor in the liver thereby decreasing the amount of fat that has built up in the liver and potentially reducing the inflammation that is associated with NASH. In Phase 2 studies in patients with NASH, patients received resmetirom or placebo (a pill that looks like resmetirom but has no active ingredient). As compared with placebo, resmetirom reduced NASH as determined by a test, called a liver biopsy. Resmetirom also had multiple other potentially beneficial effects such as reducing the fat in the liver, reducing the level of “bad cholesterol” and triglycerides in the blood, and reducing the level in the blood of markers that are signs of liver injury or scarring. Resmetirom was well-tolerated in the NASH study and other human studies.
The MAESTRO-NASH Phase 3 study is to test the safety and effectiveness of the study drug called resmetirom in a larger number of patients with NASH and fibrosis (scar tissue in the liver). About two-thirds of patients will receive resmetirom and one third placebo by random assignment. The study is blinded, meaning that doctors, patients or other study personnel involved in the study will not know whether resmetirom or placebo was assigned to a given patient.
The purpose of this study is to determine:
- How well resmetirom works for the treatment of NASH with scarring compared to a placebo.
- The safety of the study drug in participants with NASH.
The study lasts up to four and a half years. After about 900 patients complete the first year of the trial, additional information about the effect of the drug may become available.
You may be eligible to participate if you are likely to have NASH or have been diagnosed with NASH. In the first part of the study your study doctor will run some tests to determine if you have NASH and evidence of liver fibrosis.
Resmetirom is an investigational drug. This means that it is still being studied and that it has not been approved by the U.S. Food and Drug Administration (FDA) for the treatment of NASH. The FDA only allows resmetirom to be used in research.