Rezdiffra® With Concomitant Therapies Commonly Used to Treat Comorbidities in Adults With MASH and F2-F3 Fibrosis
A Phase 4, Open-label, Multi-group Study of Rezdiffra® in Combination With Concomitant Therapies Commonly Used to Treat Comorbidities in Adults With MASH and Moderate to Advanced (F2-F3) Fibrosis, Administered According to Their Approved Labeling
To determine the safety of Rezdiffra (Resmetirom) when administered alongside common prescriptions for Diabetes Metellus (Farxiga/dapagliflozin & Actos/pioglitazone)
Aperçu de l'étude
Statut
Intervention / Traitement
Description détaillée
This Phase 4 study will evaluate the safety and tolerability of REZDIFFRA® (resmetirom) when used in combination with concomitant therapies commonly used to treat diabetes in adults with metabolic dysfunction-associated steatohepatitis (MASH) and noncirrhotic, moderate-to-advanced (F2-F3) fibrosis. The concomitant therapies evaluated in this study will include ACTOS®/pioglitazone and FARXIGA®/dapagliflozin. All study medications will be administered according to their approved labeling.
Participants will be assigned to one of six cohorts based on their existing therapy and the concomitant medication being evaluated. In Group A, participants who are receiving a stable dose of pioglitazone or dapagliflozin will initiate resmetirom. In Group B, participants who are receiving a stable dose of REZDIFFRA will initiate pioglitazone or dapagliflozin. In Group C, participants who are not currently receiving either treatment will initiate resmetirom and either pioglitazone or dapagliflozin in a staggered manner, with a 4- to 6-week run-in period between initiation of the first and second medications.
Approximately 25 participants are planned for each of the six cohorts, for a maximum planned enrollment of approximately 150 participants. Following initiation of combination treatment, participants will be followed for 24 weeks, with a safety follow-up visit approximately 4 weeks after completion of treatment.
Safety and tolerability will be characterized through assessment of treatment-emergent adverse events, physical examinations, vital signs, clinical laboratory parameters, treatment discontinuations, and dose interruptions or reductions. Exploratory assessments will evaluate changes in liver fat by MRI-PDFF, noninvasive measures of hepatic steatosis and fibrosis, and biomarkers related to MASH disease state, insulin resistance, glucose homeostasis, body weight, and liver function.
Type d'étude
Inscription (Estimé)
Phase
- Phase 4
Contacts et emplacements
Coordonnées de l'étude
- Nom: Tom Hare
- Numéro de téléphone: 267-406-0611
- E-mail: info@madrigalpharma.com
Lieux d'étude
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Arizona
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Chandler, Arizona, États-Unis, 85224
- Pas encore de recrutement
- Arizona Liver Health - Chandler
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Arkansas
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North Little Rock, Arkansas, États-Unis, 72117
- Pas encore de recrutement
- Arkansas Gastroenterology
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California
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Coronado, California, États-Unis, 92118
- Pas encore de recrutement
- Southern California Research Center
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Rialto, California, États-Unis, 37411
- Pas encore de recrutement
- Inland Empire Liver Foundation
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Florida
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Lakewood Rch, Florida, États-Unis, 34211
- Pas encore de recrutement
- Florida Research Institute
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Miami, Florida, États-Unis, 33176
- Recrutement
- Gastro Health PLLC Galloway
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Miami, Florida, États-Unis, 33186
- Pas encore de recrutement
- Med Research of Florida, LLC
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Louisiana
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Lake Charles, Louisiana, États-Unis, 70605
- Recrutement
- Elevate Clinical Research
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North Carolina
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Morehead City, North Carolina, États-Unis, 28557
- Pas encore de recrutement
- Centricity Research - Morehead City - Multispecialty - PPDS
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Ohio
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Cincinnati, Ohio, États-Unis, 45219
- Recrutement
- Gastro Health Research
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Tennessee
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Chattanooga, Tennessee, États-Unis, 37411
- Pas encore de recrutement
- University Diabetes and Endocrine Consultants
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Texas
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Arlington, Texas, États-Unis, 76012-3216
- Pas encore de recrutement
- Texas Clinical Research Institute
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Corpus Christi, Texas, États-Unis, 78414
- Pas encore de recrutement
- South Texas Endocrinology & Metabolism Center
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Dallas, Texas, États-Unis, 75234
- Pas encore de recrutement
- The Liver Institute at Methodist Dallas Medical Center
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McAllen, Texas, États-Unis, 78504
- Pas encore de recrutement
- Elevate Clinical Research - McAllen - PPDS
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San Antonio, Texas, États-Unis, 78229
- Pas encore de recrutement
- Diabetes and Glandular Disease Clinic, PA
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria
All Subjects:
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Willing to participate in the study and provide written informed consent.
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Meets all requirements per REZDIFFRA Prescribing Information, in the opinion of the PI.
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Male and female adults ≥18 of age at time of screening.
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Evidence of hepatic steatosis consistent with MASH demonstrated by an MRI-PDFF fat fraction >5% obtained during second screening period.
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Evidence of moderate-to-advanced fibrosis (F2-F3) without cirrhosis.
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Stable medical conditions and background medications (non-concomitant medications as defined in this protocol) per PI judgement.
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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.
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Must be taking a stable dose of ACTOS/pioglitazone for at least 2 months prior to Baseline. (Group A1)
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Must be taking a stable dose of FARXIGA/dapagliflozin for at least 2 months prior to Baseline. (Group A2)
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Must be taking a stable dose of REZDIFFRA for at least 2 months prior to Baseline. (Groups B1 and B2)
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Must not have previously taken RESMETIROM or ACTOS/pioglitazone or FARXIGA/dapagliflozin. (Group C)
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For Groups A1, B1, and C1: Meets all requirements per ACTOS/pioglitazone Prescribing Information, in the opinion of the PI.
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For Groups B1 and C1: (ie, naïve to ACTOS/pioglitazone): HbA1c at screening ≥7.0% and ≤10.0%.
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For Groups A2, B2, and C2: Meets all requirements per FARXIGA/dapagliflozin Prescribing Information, in the opinion of the PI.
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For Groups B2 and C2 (ie, naïve to FARXIGA/dapagliflozin): HbA1c at screening ≥7.0% and ≤10.0%.
Exclusion Criteria All subjects
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Off label use of the commercially available study medications.
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Evidence of cirrhosis demonstrated by clinical, imaging, histologic, or NIT thresholds consistent with cirrhosis.
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Other chronic liver diseases (eg, viral hepatitis, autoimmune hepatitis, hemochromatosis).
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Documented history of decompensated liver disease.
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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.
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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.
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Active or suspected bladder cancer.
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Diagnosis of heart failure.
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eGFR < 60mL/min/1.73 m2
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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.
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Individuals who are currently incarcerated or who are anticipated to be incarcerated during the study period.
Groups B and C:
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Unable to secure a prescription for a concomitant medication.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Autre: Actos (pioglitazone) [Ongoing] | Resmetirom [New]
Experienced Actos/Pioglitazone + Resmetirom Naive (A1) |
Resmetirom - weight-based dosing:
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 |
|
Autre: Farxiga (dapagliflozin) [Ongoing] | Resmetirom [New]
Experienced Farxiga/Dapagliflozin + Resmetirom Naive (A2) |
Resmetirom - weight-based dosing:
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) |
|
Autre: REZDIFFRA [Ongoing] | Actos (pioglitazone) [New]
Experienced REZDIFFRA + Actos/Pioglitazone Naive (B1) |
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 All study medications will be administered according to their labels: • REZDIFFRA- Label weight-based dosing:
|
|
Autre: REZDIFFRA [Ongoing] | Farxiga (dapagliflozin) [New]
Experienced REZDIFFRA + Farxiga/Dapagliflozin Naive (B2) |
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) All study medications will be administered according to their labels: • REZDIFFRA- Label weight-based dosing:
|
|
Autre: Actos (pioglitazone) [New] | Resmetirom [New]
Naive Actos/Pioglitazone + Resmetirom Naive (C2) |
Resmetirom - weight-based dosing:
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 |
|
Autre: Farxiga (dapagliflozin) [New] | Resmetirom [New]
Naïve Farxiga/dapagliflozin + Resmetirom Naïve (C2) |
Resmetirom - weight-based dosing:
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) |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
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Number and Percentage of Participants With Treatment-Emergent Adverse Events (TEAEs)
Délai: From First Dose of newly introduced medication up to 28 weeks
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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
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Number and Percentage of Participants With TEAEs by Maximum Severity
Délai: From First Dose of newly introduced medication up to 28 weeks
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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
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Number and Percentage of Participants With TEAEs by Relationship to Study Medication
Délai: From First Dose of newly introduced medication up to 28 weeks
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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
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Directeur d'études: Tom Hare, Madrigal Pharmaceuticals, Inc.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Réel)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- MGL-3196-33
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
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