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NCT Number: NCT07830758

Resmetirom in Patients With MASH and HFpEF

This Phase 1b multicenter randomized double-blind placebo-controlled study evaluates the safety, tolerability and hepatic pharmacodynamic effects of resmetirom in adults with metabolic dysfunction-associated steatohepatitis (MASH) and heart failure with preserved ejection fraction (HFpEF). Participants are randomized 2:1 to resmetirom or placebo for 24 weeks.

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Key information

Conditions

MASH - Metabolic Dysfunction-Associated Steatohepatitis Heart Failure With Preserved Ejection Fraction (HFpEF)

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Resmetirom

Drug

Resmetirom (80 mg or 100 mg orally once daily based on body weight)

Placebo

Drug

Matching placebo orally once daily

Primary outcomes

  1. Incidence of treatment-emergent adverse events (TEAEs)

    Time frame: From first dose through End of Study follow-up (28 days after last dose)

  2. Incidence of treatment-emergent serious adverse events (SAES)

    Time frame: From first dose through End of Study follow-up (28 days after last dose)

  3. Change from baseline in physical examination findings assessed by investigator physical examination

    Time frame: Baseline to Week 24

    Physical examination findings will be assessed by the Investigator and include general appearance, skin, head and neck, heart, lungs, abdomen, extremities, and neuromuscular assessments. After Screening and successful Randomization, physical examinations may be targeted to evaluation of new symptoms or signs.

  4. Change from baseline in body temperature

    Time frame: Baseline to Week 24

    Body temperature will be measure in °C, resting heart rate in beats per minute, respiratory rate in breaths per minute, systolic blood pressure in mmHg, and diastolic blood pressure in mmHg

  5. Change from baseline resting heart rate

    Time frame: Baseline to Week 24

    Resting heart rate will be measured in beats per minute (bpm)

  6. Change from baseline in respiratory rate

    Time frame: Baseline to Week 24

    Respiratory rate will be measured in breaths per minute.

  7. Change from baseline in seated systolic blood pressure

    Time frame: Baseline to Week 24

    Resting seated systolic blood pressure will be measured in millimeters of mercury (mmHg)

  8. Change from baseline in seated diastolic blood pressure

    Time frame: Baseline to Week 24

    Resting seated diastolic blood pressure will be measured in millimeters of mercury (mmHg)

  9. Change from baseline in PR interval on 12-lead ECG in milliseconds (ms)

    Time frame: Baseline to Week 24

  10. Change from baseline in QRS interval on 12-lead ECG in milliseconds (ms)

    Time frame: Baseline to Week 24

  11. Change from baseline in heart rate on 12-lead ECG in beats per minute (bpm)

    Time frame: Baseline to Week 24

  12. Change from baseline in RR interval on 12-lead ECG in milliseconds (ms)

    Time frame: Baseline to Week 24

  13. Change from baseline in QT interval on 12-lead ECG in milliseconds (ms)

    Time frame: Baseline to Week 24

  14. Change from baseline in QT interval corrected using Bazett's formula (QTcB) in milliseconds (ms)

    Time frame: Baseline to Week 24

  15. Change from baseline in QT interval corrected using Fridericia's formula (QTcF) in milliseconds (ms)

    Time frame: Baseline to Week 24

  16. Number of participants with clinically significant abnormalities in hematology laboratory parameters

    Time frame: Baseline to Week 24

    Hematology laboratory parameters include hemoglobin, hematocrit, red blood cell count, white blood cell count, platelet count, red blood cell indices, and differential leukocyte counts. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.

  17. Number of participants with clinically significant abnormalities in blood chemistry laboratory parameters

    Time frame: Baseline to Week 24

    Blood chemistry laboratory parameters include measures of hepatic function, renal function, glucose metabolism, pancreatic function, electrolytes, bilirubin, and serum proteins. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.

  18. Number of participants with clinically significant abnormalities in urinalysis parameters

    Time frame: Baseline to Week 24

    Urinalysis parameters include pH, specific gravity, protein, glucose, ketones, bilirubin, blood, nitrite, urobilinogen, and leukocyte esterase. The number of participants with clinically significant abnormalities, as determined by the Investigator, will be summarized by treatment group.

  19. Percent change from baseline in liver fat content measured by MRI-Proton Density Fat Fraction (MRI-PDFF)

    Time frame: Baseline to Week 24

Study contacts

Contact information is provided by the study sponsor or research team.

Ashley Magnavita

CONTACT

[email protected]

+1 267-806-1293

Sponsors and collaborators

Lead sponsor

Madrigal Pharmaceuticals, Inc.

Industry

Registry information

Official study title

A Phase 1b, Multi-Center, Double-Blind (Sponsor Unblinded), Randomized, Placebo-Controlled Study of the Safety, Tolerability, and Hepatic Pharmacodynamics of Resmetirom in Patients With Metabolic Dysfunction-Associated Steatohepatitis (MASH) and Heart Failure With Preserved Ejection Fraction (HFpEF)

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Sep 21, 2026
Registry last updated
Sep 21, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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