Clinical Research Studies

This is a multi-national, multicenter, double-blind, randomized, placebo-controlled study in patients with well-compensated NASH cirrhosis (CP-A, see Child-Pugh Classification, Appendix 6). Study subjects must have at least three metabolic risk factors for NASH cirrhosis, as defined in Section 6.1 Pre-Screening Criteria. The diagnosis of histologic NASH cirrhosis is defined as one of the following: (A) NASH cirrhosis on most recent biopsy (within last 5 years). This group is estimated to be approximately 70% of the study population. (B) Historical biopsy shows NASH with significant fibrosis, now with progression to cirrhosis based on clinical diagnosis. This group is estimated to be approximately 20% of the study population. (C) Historical biopsy shows NASH with steatosis, now with progression to cirrhosis based on clinical diagnosis. This group is estimated to be approximately 10% of the study population (see Section 6.2 for additional details). To be eligible for this study, patients must have a diagnosis of well-compensated NASH cirrhosis (CP-A) with either normal liver function or mild hepatic impairment, and no history of a hepatic decompensation event. A CP-A (score of 5 to 6) is considered well-compensated disease. Patients who qualify for study inclusion 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 events are achieved, approximately 3 years). The randomization will be stratified by 3 factors: (1) baseline Type 2 diabetes (T2D) status (presence/absence); (2) MRI-PDFF (=5%, >5%) or, when MRI-PDFF is unavailable/contraindicated, CAP (<300, =300); and (3) MRE (<6, =6) or, when MRE is unavailable/contraindicated, ELF (<11.3, =11.3). This study comprises an up to 60-day screening period and an approximately 3-year treatment period. However, the study will continue until a sufficient number of confirmed adjudicated Composite Clinical Outcome events (primary endpoint) have accrued in patients. This is estimated to be approximately 92 events. Study assessments will be performed every 4 weeks through the first 16 weeks of the study treatment period, and then every 12 weeks until Week 52 and every 3 months thereafter for the duration of the study.