A clinical trial to evaluate the safety and effectiveness of MGL-3196 (resmetirom) in patients with Non-Alcoholic Steatohepatitis (NASH) and reduce progression of liver damage and resolve NASH

INTERVENTION: Product Name: Matching placebo MGL‐3196 60 mg film‐coated tablet, Matching placebo MGL‐3196 80 mg film‐coated tablet, Matching placebo MGL‐3196 100 mg film‐coated tablet., Product Code:N/A, Pharmaceutical Form: N/A, Other descriptive name: N/A , Strength: , Pharmaceutical form of the placebo: N/A , Product Name: MGL‐3196 100 mg oral, Product Code:PRD10931295, Pharmaceutical Form: FILM‐COATED TABLET, Other descriptive name: , Strength: , Product Name: MGL‐3196 80 mg oral, Product Code:PRD10931294, Pharmaceutical Form: FILM‐COATED TABLET, Other descriptive name: , Strength: , Product Name: MGL‐3196 60 mg oral, Product Code:PRD4683991, Pharmaceutical Form: FILM‐COATED TABLET, Other descriptive name: , Strength: CONDITION: MedDRA version: 24.1Level: PTClassification code: 10053219Term: Non‐alcoholic steatohepatitis Class: 100000004871 Non‐Alcoholic Steatohepatitis (NASH) ; MedDRA version: 24.1Level: PTClassification code: 10053219Term: Non‐alcoholic steatohepatitis Class: 100000004871 Therapeutic area: Diseases [C] ‐ Digestive System Diseases [C06] PRIMARY OUTCOME: Main Objective: Week 52 Dual Primary Objectives: ; To determine the effect once‐daily, oral administration of 80 mg or 100 mg MGL‐3196 versus matching placebo on NASH, as measured by:; 1. The resolution of NASH associated with an at least 2‐point reduction in NAFLD activity score (NAS) and without worsening of fibrosis by liver biopsy after 52 weeks of treatment (Week 52 Primary endpoint) in the mITT‐LB‐W52 population.; Resolution includes:; ‐ The absence of balloning (score = 0) and absent or mild lobular inflammation (score 0 to 1; associated with at least 2‐point reduction in NAS).; ‐ No worsening of fibrosis: worsening of fibrosis is defined as any progression = 1 stage.; 2. The histological improvement from Baseline demonstrated by at least a 1‐point improvement in fibrosis by liver biopsy with no worsening of NAS at Week 52.; Month 54 Primary Objective:; Time to experiencing an adjudicated Composite Clinical Outcome event Primary end point(s): Week 52 Dual Primary endpoints: NASH Resolution Response at Week 52 Fibrosis = 1 Stage Responder at Week 52, Time to Composite Clinical Outcome Event at Month 54 Secondary Objective: Key Secondary objective: For the Week 52 analysis, the key secondary objective is to determine the effect of once‐daily, oral administration of 80 mg or 100 mg MGL‐3196 versus matching placebo on the percent change from Baseline at 24 weeks in directly measured low‐density lipoprotein cholesterol (LDL‐C). SECONDARY OUTCOME: Secondary end point(s):Percent change from baseline in directly measured LDL‐C at Week 24 and Week 52 INCLUSION CRITERIA: Must be willing to participate in the study and provide written informed consent, Male and female adults =18 years of age., Female patients are eligible if they are of reproductive potential and have a negative serum pregnancy test, are not breastfeeding, and do not plan to become pregnant during the study and agree to use 2 highly effective birth control methods during the study OR if they are not of child bearing potential or naturally sterile. Highly effective birth control methods include condoms with spermicide, diaphragm with spermicide, hormonal and non‐hormonal intrauterine device, hormonal contraception (estrogens stable = 3 months), a vasectomized or sterile male partner, or sexual abstinence (defined as refraining from heterosexual intercourse), from Screening throughout the study and for at least 30 days after study drug administration. Reliance on abstinence from heterosexual intercourse is acceptable only if it is subject`s habitual practice., Male sub