Resmetirom in Patients With MASH and HFpEF

Inclusion Criteria

• 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.

Exclusion Criteria

• Patients with cirrhosis and other etiologies of chronic liver disease
• 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.
• Thyroid disease:

• Active hyperthyroidism
• Untreated clinical hypothyroidism defined by TSH >7 IU/L with symptoms of hypothyroidism or >10 IU/L without symptoms
• 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
• HbA1c >9.0%
• Diagnosis of HCC
• 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
• 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.
• 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
• Confirmed QTcF >450 msec for males and >470 msec for females at the Screening ECG assessment;
• Presence of sustained atrial fibrillation at time of Screening or history of paroxysmal atrial fibrillation episodes for the last 3 months prior to Screening