Rezdiffra® With Concomitant Therapies Commonly Used to Treat Comorbidities in Adults With MASH and F2-F3 Fibrosis

NCT07848191 | Not Yet Recruiting Phase 4 FDA Drug

• 1 other identifier: MGL-3196-33
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine the safety of Rezdiffra (Resmetirom) when administered alongside common prescriptions for Diabetes Metellus (Farxiga/dapagliflozin \& Actos/pioglitazone)

Conditions

MASH - Metabolic Dysfunction-Associated Steatohepatitis

Outcome Measures

Primary Outcomes (3)

• Number and Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)

  The total number of TEAEs and the number and percentage of participants with at least 1 TEAE will be summarized by study group. TEAEs will also be summarized by System Organ Class and Preferred Term.

  From First Dose of newly introduced medication up to 28 weeks

• Number and Percentage of Participants With TEAEs by Maximum Severity

  The number and percentage of participants with TEAEs will be summarized by maximum severity using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0.

  From First Dose of newly introduced medication up to 28 weeks

• Number and Percentage of Participants With TEAEs by Relationship to Study Medication

  The number and percentage of participants with TEAEs assessed as Related or Not Related to each applicable study medication (REZDIFFRA/resmetirom, ACTOS/pioglitazone, or FARXIGA/dapagliflozin) will be summarized by study group.

  From First Dose of newly introduced medication up to 28 weeks

Study Arms (6)

Actos (pioglitazone) [Ongoing] | Resmetirom [New]

OTHER

Experienced Actos/Pioglitazone + Resmetirom Naive (A1)

Drug: Resmetirom; Drug: ACTOS/pioglitazone

Farxiga (dapagliflozin) [Ongoing] | Resmetirom [New]

OTHER

Experienced Farxiga/Dapagliflozin + Resmetirom Naive (A2)

Drug: Resmetirom; Drug: FARXIGA/dapagliflozin

REZDIFFRA [Ongoing] | Actos (pioglitazone) [New]

OTHER

Experienced REZDIFFRA + Actos/Pioglitazone Naive (B1)

Drug: Rezdiffra; Drug: ACTOS/pioglitazone

REZDIFFRA [Ongoing] | Farxiga (dapagliflozin) [New]

OTHER

Experienced REZDIFFRA + Farxiga/Dapagliflozin Naive (B2)

Drug: Rezdiffra; Drug: FARXIGA/dapagliflozin

Actos (pioglitazone) [New] | Resmetirom [New]

OTHER

Naive Actos/Pioglitazone + Resmetirom Naive (C2)

Drug: Resmetirom; Drug: ACTOS/pioglitazone

Farxiga (dapagliflozin) [New] | Resmetirom [New]

OTHER

Naïve Farxiga/dapagliflozin + Resmetirom Naïve (C2)

Drug: Resmetirom; Drug: FARXIGA/dapagliflozin

Interventions

Rezdiffra DRUG

All study medications will be administered according to their labels: • REZDIFFRA- Label weight-based dosing: * \<100 kg: 80 mg orally once daily. * ≥100 kg: 100 mg orally once daily

REZDIFFRA [Ongoing] | Actos (pioglitazone) [New]; REZDIFFRA [Ongoing] | Farxiga (dapagliflozin) [New]

Resmetirom DRUG

Resmetirom - weight-based dosing: * \<100 kg: 80 mg orally once daily. * ≥100 kg: 100 mg orally once daily

Actos (pioglitazone) [New] | Resmetirom [New]; Actos (pioglitazone) [Ongoing] | Resmetirom [New]; Farxiga (dapagliflozin) [New] | Resmetirom [New]; Farxiga (dapagliflozin) [Ongoing] | Resmetirom [New]

ACTOS/pioglitazone DRUG

Label dosing recommendations indicated for patients without congestive heart failure (15 or 30 mg orally once daily; if tolerated, increase by 15 mg increments up to a maximum of 45 mg orally once daily for additional glycemic control

Actos (pioglitazone) [New] | Resmetirom [New]; Actos (pioglitazone) [Ongoing] | Resmetirom [New]; REZDIFFRA [Ongoing] | Actos (pioglitazone) [New]

FARXIGA/dapagliflozin DRUG

Label dosing recommendations indicated for glycemic control in type 2 diabetes (5 mg orally once daily; if tolerated, increase to 10 mg orally once daily for additional glycemic control)

Farxiga (dapagliflozin) [New] | Resmetirom [New]; Farxiga (dapagliflozin) [Ongoing] | Resmetirom [New]; REZDIFFRA [Ongoing] | Farxiga (dapagliflozin) [New]

Eligibility Criteria

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

You may qualify if:

• All Subjects:
• Willing to participate in the study and provide written informed consent.
• Meets all requirements per REZDIFFRA Prescribing Information, in the opinion of the PI.
• Male and female adults ≥18 of age at time of screening.
• Evidence of hepatic steatosis consistent with MASH demonstrated by an MRI-PDFF fat fraction \>5% obtained during second screening period.
• Evidence of moderate-to-advanced fibrosis (F2-F3) without cirrhosis.
• Stable medical conditions and background medications (non-concomitant medications as defined in this protocol) per PI judgement.
• Female subjects 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 newly introduced medication 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 newly introduced medication administration. Reliance on abstinence from heterosexual intercourse is acceptable only if it is the subject's habitual practice. NOTE: Female subjects who are not of child-bearing potential (ie, surgically \[bilateral oophorectomy, hysterectomy\] or naturally sterile \[\>12 consecutive months without menses\]) do not require contraception during the study.
• Must be taking a stable dose of ACTOS/pioglitazone for at least 2 months prior to Baseline. (Group A1)
• Must be taking a stable dose of FARXIGA/dapagliflozin for at least 2 months prior to Baseline. (Group A2)
• Must be taking a stable dose of REZDIFFRA for at least 2 months prior to Baseline. (Groups B1 and B2)
• Must not have previously taken RESMETIROM or ACTOS/pioglitazone or FARXIGA/dapagliflozin. (Group C)
• For Groups A1, B1, and C1: Meets all requirements per ACTOS/pioglitazone Prescribing Information, in the opinion of the PI.
• For Groups B1 and C1: (ie, naïve to ACTOS/pioglitazone): HbA1c at screening ≥7.0% and ≤10.0%.

You may not qualify if:

• Off label use of the commercially available study medications.
• Evidence of cirrhosis demonstrated by clinical, imaging, histologic, or NIT thresholds consistent with cirrhosis.
• Other chronic liver diseases (eg, viral hepatitis, autoimmune hepatitis, hemochromatosis).
• Documented history of decompensated liver disease.
• Use of rosuvastatin or simvastatin at a dose greater than 20 mg/day, or pravastatin or atorvastatin at a dose greater than 40 mg/day, at the time of the first dose of resmetirom. Subjects receiving a statin dose above the applicable limit during the screening period may remain eligible if the dose is reduced to the applicable maximum permitted dose before the first dose of resmetirom.
• Any other condition which, in the opinion of the investigator, would impede compliance, hinder completion of the study, compromise the well-being of the subject, or interfere with the study outcomes.
• Active or suspected bladder cancer.
• Diagnosis of heart failure.
• eGFR \< 60mL/min/1.73 m2
• Developmental/intellectual disability, limited capacity of recognition, any history of clinically important emotional and/or psychiatric illness, inability to follow the study procedures, or any other condition which, in the opinion of the Investigator, would impede compliance, hinder completion of the study, compromise the well-being of the patient, or interfere with the study outcomes.
• Individuals who are currently incarcerated or who are anticipated to be incarcerated during the study period.
• Groups B and C:
• Unable to secure a prescription for a concomitant medication.

Sponsors & Collaborators

• Madrigal Pharmaceuticals, Inc.: lead

MeSH Terms

Interventions

resmetirom; Pioglitazone; dapagliflozin

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Tom Hare

  Madrigal Pharmaceuticals, Inc.

  STUDY DIRECTOR

Central Study Contacts

Tom Hare

CONTACT

267-406-0611; info@madrigalpharma.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2026
• First Posted: September 29, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: September 29, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share