MASH - Metabolic Dysfunction-Associated SteatohepatitisPhase 1NCT07830758
Resmetirom in Patients With MASH and HFpEF
A Phase 1 study testing Resmetirom in people with MASH - Metabolic Dysfunction-Associated Steatohepatitis and Heart Failure With Preserved Ejection Fraction (HFPEF), run by Madrigal Pharmaceuticals, Inc. at 5 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- MASH - Metabolic Dysfunction-Associated Steatohepatitis, Heart Failure With Preserved Ejection Fraction (HFPEF)
- What is being tested?
- Resmetirom
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 90 participants
- Where
- 5 sitesUnited States
- Study dates
- Sep 2026to Dec 2027
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
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- 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
Trial locations and contacts
5 sites in 1 country. Contact the study team or a site near you to ask about taking part.
5 sites in 1 country
United States5 sites, 5 recruiting
- Recruiting
Covenant Metabolic Specialist
Fort Myers, Florida, 33912
- Recruiting
FOMAT - Clinicas Mi Salud
Oxnard, California, 93030
- Recruiting
Arizona Clinical Trials
Peoria, Arizona, 85382
- Recruiting
Covenant Metabolic Specialist
Riverview, Florida, 33578
- Recruiting
Covenant Metabolic Specialist
University Park, Florida, 34201
About this study
Official 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)
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
- MASH - Metabolic Dysfunction-Associated Steatohepatitis, Heart Failure With Preserved Ejection Fraction (HFPEF)
- Being tested
- Resmetirom, Placebo
- Keywords
- MASH, HFPEF
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ResmetiromDrug
Resmetirom (80 mg or 100 mg orally once daily based on body weight)
PlaceboDrug
Matching placebo orally once daily
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: Drug: Resmetirom |
| Arm 2 - Placebo Comparator | Placebo comparator | Participants will receive matching placebo orally once daily for 24 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-emergent adverse events (TEAEs)
Measured: From first dose through End of Study follow-up (28 days after last dose)
Incidence of treatment-emergent serious adverse events (SAES)
Measured: 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.
Measured: 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
Measured: Baseline to Week 24
Change from baseline resting heart rate
Resting heart rate will be measured in beats per minute (bpm)
Measured: Baseline to Week 24
Change from baseline in respiratory rate
Respiratory rate will be measured in breaths per minute.
Measured: 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)
Measured: 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)
Measured: Baseline to Week 24
Change from baseline in PR interval on 12-lead ECG in milliseconds (ms)
Measured: Baseline to Week 24
Change from baseline in QRS interval on 12-lead ECG in milliseconds (ms)
Measured: Baseline to Week 24
Change from baseline in heart rate on 12-lead ECG in beats per minute (bpm)
Measured: Baseline to Week 24
Change from baseline in RR interval on 12-lead ECG in milliseconds (ms)
Measured: Baseline to Week 24
Change from baseline in QT interval on 12-lead ECG in milliseconds (ms)
Measured: Baseline to Week 24
Change from baseline in QT interval corrected using Bazett's formula (QTcB) in milliseconds (ms)
Measured: Baseline to Week 24
Change from baseline in QT interval corrected using Fridericia's formula (QTcF) in milliseconds (ms)
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline to Week 24
Percent change from baseline in liver fat content measured by MRI-Proton Density Fat Fraction (MRI-PDFF)
Measured: Baseline to Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2026
- Study startSep 2026 (estimated)
- Primary completionNov 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MASH - Metabolic Dysfunction-Associated SteatohepatitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 90 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Madrigal Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Uli Frevert, MD, Study director, Madrigal Pharmaceuticals, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07830758
- Sponsor's protocol ID
- MGL-3196-34
- Status last verified
- Oct 2026
- First submitted
- 25 Aug 2026
- Last updated
- 16 Oct 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No