Recruiting
Phase 4
Rezdiffra® With Concomitant Therapies Commonly Used to Treat Comorbidities in Adults With MASH and F2-F3 Fibrosis
Condition(s) studied
MASH - Metabolic Dysfunction-Associated Steatohepatitis
Investigational drug(s) / intervention(s)
Rezdiffra: 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
Resmetirom: Resmetirom - weight-based dosing:
* \<100 kg: 80 mg orally once daily.
* ≥100 kg: 100 mg orally once daily
ACTOS/pioglitazone: 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
FARXIGA/dapagliflozin: 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)
Study summary
To determine the safety of Rezdiffra (Resmetirom) when administered alongside common prescriptions for Diabetes Metellus (Farxiga/dapagliflozin \& Actos/pioglitazone)
Eligibility
Inclusion Criteria
All Subjects:
1. Willing to participate in the study and provide written informed consent.
2. Meets all requirements per REZDIFFRA Prescribing Information, in the opinion of the PI.
3. Male and female adults ≥18 of age at time of screening.
4. Evidence of hepatic steatosis consistent with MASH demonstrated by an MRI-PDFF fat fraction \>5% obtained during second screening period.
5. Evidence of moderate-to-advanced fibrosis (F2-F3) without cirrhosis.
6. Stable medical conditions and background medications (non-concomitant medications as defined in this protocol) per PI judgement.
7. 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.
8. Must be taking a stable dose of ACTOS/pioglitazone for at least 2 months prior to Baseline. (Group A1)
9. Must be taking a stable dose of FARXIGA/dapagliflozin for at least 2 months prior to Baseline. (Group A2)
10. Must be taking a stable dose of REZDIFFRA for at least 2 months prior to Baseline. (Groups B1 and B2)
11. Must not have previously taken RESMETIROM or ACTOS/pioglitazone or FARXIGA/dapagliflozin. (Group C)
12. For Groups A1, B1, and C1: Meets all requirements per ACTOS/pioglitazone Prescribing Information, in the opinion of the PI.
13. For Groups B1 and C1: (ie, naïve to ACTOS/pioglitazone): HbA1c at screening ≥7.0% and ≤10.0%.
14. For Groups A2, B2, and C2: Meets all requirements per FARXIGA/dapagliflozin Prescribing Information, in the opinion of the PI.
15. For Groups B2 and C2 (ie, naïve to FARXIGA/dapagliflozin): HbA1c at screening ≥7.0% and ≤10.0%.
Exclusion Criteria All subjects
1. Off label use of the commercially available study medications.
2. Evidence of cirrhosis demonstrated by clinical, imaging, histologic, or NIT thresholds consistent with cirrhosis.
3. Other chronic liver diseases (eg, viral hepatitis, autoimmune hepatitis, hemochromatosis).
4. Documented history of decompensated liver disease.
5. 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.
6. 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.
7. Active or suspected bladder cancer.
8. Diagnosis of heart failure.
9. eGFR \< 60mL/min/1.73 m2
10. 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.
11. Individuals who are currently incarcerated or who are anticipated to be incarcerated during the study period.
Groups B and C:
12. Unable to secure a prescription for a concomitant medication.
Primary outcome measure(s)
- Number and Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs) — From First Dose of newly introduced medication up to 28 weeks
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.
- Number and Percentage of Participants With TEAEs by Maximum Severity — From First Dose of newly introduced medication up to 28 weeks
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.
- Number and Percentage of Participants With TEAEs by Relationship to Study Medication — From First Dose of newly introduced medication up to 28 weeks
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.
Trial sites (16)
| Facility | City | Region | Status |
| Arizona Liver Health - Chandler |
Chandler |
Arizona |
Not Yet Recruiting |
| Arkansas Gastroenterology |
North Little Rock |
Arkansas |
Not Yet Recruiting |
| Southern California Research Center |
Coronado |
California |
Not Yet Recruiting |
| Inland Empire Liver Foundation |
Rialto |
California |
Not Yet Recruiting |
| Florida Research Institute |
Lakewood Rch |
Florida |
Not Yet Recruiting |
| Gastro Health PLLC Galloway |
Miami |
Florida |
Recruiting |
| Med Research of Florida, LLC |
Miami |
Florida |
Not Yet Recruiting |
| Elevate Clinical Research |
Lake Charles |
Louisiana |
Recruiting |
| Centricity Research - Morehead City - Multispecialty - PPDS |
Morehead City |
North Carolina |
Not Yet Recruiting |
| Gastro Health Research |
Cincinnati |
Ohio |
Recruiting |
| University Diabetes and Endocrine Consultants |
Chattanooga |
Tennessee |
Not Yet Recruiting |
| Texas Clinical Research Institute |
Arlington |
Texas |
Not Yet Recruiting |
| South Texas Endocrinology & Metabolism Center |
Corpus Christi |
Texas |
Not Yet Recruiting |
| The Liver Institute at Methodist Dallas Medical Center |
Dallas |
Texas |
Not Yet Recruiting |
| Elevate Clinical Research - McAllen - PPDS |
McAllen |
Texas |
Not Yet Recruiting |
| Diabetes and Glandular Disease Clinic, PA |
San Antonio |
Texas |
Not Yet Recruiting |
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