MGL-3196-34

Currently Recruiting: Participants

Study Drug/Intervention: Resmetirom

Anticipated Sample Size: 90 Participants

Study Timeline: This study is expected to conclude in May 2027.

ClinicalTrials.gov ID: NCT07830758

Study Objective

The goals of this study are to: (1) enhance currently available resmetirom safety, tolerability, and hepatic pharmacodynamic data and (2) explore the impact of resmetirom on cardiac function in a cohort of patients with MASH and HFpEF. Descriptive observations of these data will be used to generate testable working hypotheses for future research.

Key Inclusion Criteria

1. Must be willing to participate in the study and provide written informed consent.
2. Male and female adults ≥18 years of age.
3. Suspected or confirmed diagnosis of fibrotic MASH suggested by the historical data and meets at least 1 criteria for fibrotic MASH
4. Confirmed diagnosis of HFpEF
5. Structural and/or functional heart disease based on echocardiographic evaluation.
6. eGFR ≥45 mL/min/1.73 m2
7. 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.

Key Exclusion Criteria

1. Patients with cirrhosis and other etiologies of chronic liver disease
2. 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.
3. Thyroid disease:
   1. Active hyperthyroidism
   2. Untreated clinical hypothyroidism defined by TSH >7 IU/L with symptoms of hypothyroidism or >10 IU/L without symptoms
4. History of bariatric surgery or intestinal bypass surgery within the 5 years prior to randomization or planned during the conduct of the study
5. Weight gain or loss >5% total body weight within 12 weeks prior to randomization
6. HbA1c >9.0%
7. Diagnosis of HCC
8. MELD score ≥12, as determined at Screening, due to liver disease
9. Hepatic decompensation or impairment.
10. 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
11. Serum ALT >250 U/L
12. Platelet count <140,000/mm3. Patients with platelets <140,000 and ≥120,000/mm3 are eligible if FIB-4 score <3.5.
13. History of biliary diversion
14. Uncontrolled hypertension (either treated or untreated) defined as systolic blood pressure >170 mmHg or a diastolic blood pressure >100 mmHg at Screening
15. Confirmed QTcF >450 msec for males and >470 msec for females at the Screening ECG assessment;
16. Presence of sustained atrial fibrillation at time of Screening or history of paroxysmal atrial fibrillation episodes for the last 3 months prior to Screening

Note: Other protocol-defined Inclusion/ Exclusion criteria may apply

Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as protocol waivers or exemptions, is not permitted. Patients are eligible to be included if all of the following inclusion criteria and none of the following exclusion criteria apply. Patients who do not initially meet eligibility criteria may be retested or rescreened once, based on Investigator judgment, to determine if they qualify to participate.

Duration of Study Participation

Up to 8 weeks for screening; up to 6 months

Study Sites

Five locations in the United States: Arizona, California, and Florida. Visit the ClinicalTrials.gov Study Details page to view all locations.

Individual participants could be in the study for approximately 14 to 39 months. The overall study duration is expected to be approximately 39 months.

Follow-Up

The 90-day follow-up period includes open-label apixaban administration from the end-of-treatment visit to the end-of-study visit.

Madrigal Pharmaceuticals

• Project Lead: Corbin Lynch