Resmetirom in Patients With MASH and HFpEF

NCT07830758 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: MGL-3196-34
• Study Type: interventional
• Target: 90
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

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

Keywords

MASH; HFPEF

Outcome Measures

Primary Outcomes (19)

• Incidence of treatment-emergent adverse events (TEAEs)

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

• Incidence of treatment-emergent serious adverse events (SAES)

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

• Change from baseline in physical examination findings assessed by investigator physical examination

  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.

  Baseline to Week 24

• Change from baseline in body temperature

  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

  Baseline to Week 24

• Change from baseline resting heart rate

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

  Baseline to Week 24

• Change from baseline in respiratory rate

  Respiratory rate will be measured in breaths per minute.

  Baseline to Week 24

• Change from baseline in seated systolic blood pressure

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

  Baseline to Week 24

• Change from baseline in seated diastolic blood pressure

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

  Baseline to Week 24

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

  Baseline to Week 24

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

  Baseline to Week 24

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

  Baseline to Week 24

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

  Baseline to Week 24

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

  Baseline to Week 24

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

  Baseline to Week 24

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

  Baseline to Week 24

• Number of participants with clinically significant abnormalities in hematology laboratory parameters

  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.

  Baseline to Week 24

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

  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.

  Baseline to Week 24

• Number of participants with clinically significant abnormalities in urinalysis parameters

  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.

  Baseline to Week 24

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

  Baseline to Week 24

Study Arms (2)

Arm 1 - Resmetirom

EXPERIMENTAL

Participants will receive resmetirom orally once daily for 24 weeks. Resmetirom dose will be based on actual body weight: 80 mg once daily for participants weighing \<100 kg and 100 mg once daily for participants weighing ≥100 kg. Dose reduction by 20 mg will be implemented for concomitant use of a moderate CYP2C8 inhibitor, as specified in the protocol

Drug: Resmetirom

Arm 2 - Placebo Comparator

PLACEBO COMPARATOR

Participants will receive matching placebo orally once daily for 24 weeks.

Drug: Placebo

Interventions

Resmetirom DRUG

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

Arm 1 - Resmetirom

Placebo DRUG

Matching placebo orally once daily

Arm 2 - Placebo Comparator

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

MeSH Terms

Interventions

resmetirom

Study Officials

• Uli Frevert, MD

  Madrigal Pharmaceuticals, Inc.

  STUDY DIRECTOR

Central Study Contacts

Ashley Magnavita

CONTACT

+1 267-806-1293; amagnavita@madrigalpharma.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: September 21, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: September 21, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share