Resmetirom in Patients With MASH and HFpEF

Prior treatment

• PEth value of ≥20 ng/mL measured at Screening OR history of significant alcohol consumption for a period of more than 3 consecutive months within 1 year prior to Screening.
• History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study
• Weight gain or loss \>5% total body weight within 12 weeks prior to randomization
• Presence of sustained atrial fibrillation at time of Screening or history of paroxysmal atrial fibrillation episodes for the last 3 months prior to Screening

Other illness

• Patients with cirrhosis and other etiologies of chronic liver disease
• Thyroid disease:
  • Active hyperthyroidism
  • Untreated clinical hypothyroidism defined by TSH \>7 IU/L with symptoms of hypothyroidism or \>10 IU/L without symptoms
• MELD score ≥12, as determined at Screening, due to liver disease
• Hepatic decompensation or impairment.
• Has an active autoimmune disease, including actively treated lupus, rheumatoid arthritis, inflammatory bowel disease, or autoimmune hepatitis, requiring systemic treatment within the past 12 weeks or a documented history of clinically severe autoimmune disease, including autoimmune liver disease, or a syndrome that requires systemic steroids or immunosuppressive agents
• History of biliary diversion
• Uncontrolled hypertension (either treated or untreated) defined as systolic blood pressure \>170 mmHg or a diastolic blood pressure \>100 mmHg at Screening

Lab values

• HbA1c \>9.0%
• Serum ALT \>250 U/L
• Platelet count \<140,000/mm3. Patients with platelets \<140,000 and ≥120,000/mm3 are eligible if FIB-4 score \<3.5.

Other

• Diagnosis of HCC
• Confirmed QTcF \>450 msec for males and \>470 msec for females at the Screening ECG assessment;

• Must be willing to participate in the study and provide written informed consent.
• Male and female adults ≥18 years of age.
• Suspected or confirmed diagnosis of fibrotic MASH suggested by the historical data and meets at least 1 criteria for fibrotic MASH
• Confirmed diagnosis of HFpEF
• Structural and/or functional heart disease based on echocardiographic evaluation.
• eGFR ≥45 mL/min/1.73 m2
• Female patients of reproductive potential are eligible if they have a negative serum pregnancy test (beta human chorionic gonadotropin), are not breastfeeding, and do not plan to become pregnant during the study and agree to use 1 highly effective birth control method during the study and for at least 30 days after study drug administration. Highly effective birth control methods include hormonal and non-hormonal intrauterine device, combination estrogen-progesterone hormonal contraception (oral, transdermal, or vaginal), tubal ligation, 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.