Ultrasound Biomarkers for Assessing Eligibility and Response to Resmetirom Therapy
Accuracy of Ultrasound Biomarkers for Assessing Eligibility and Response to Resmetirom Therapy Using MRI as the Reference Standard
This is a prospective, non-interventional, observational study to evaluate the accuracy of 2 US (ultrasound) biomarkers that quantify liver tissue fat and stiffness: UDFF (ultrasound-derived fat fraction) and pSWE (point shear wave elastography) for determining MRI-defined eligibility for resmetirom (REZDIFFRA®) treatment and for monitoring treatment response using MRI-PDFF (proton density fat fraction) and MRE (magnetic resonance elastography) as reference standards.
Study Centers Planned:
3 clinical practice facilities in Houston TX .
Study Rationale:
MASLD (metabolic dysfunction-associated steatotic liver disease ) is a growing global epidemic and the most common liver disease worldwide. Approximately 25% of adults in the United States alone have hepatic steatosis in the absence of significant alcohol consumption and 1 in 4 of these adults are presumed to have MASH.
MASH has a higher likelihood of progression to irreversible liver damage including cirrhosis and hepatocellular carcinoma.
Despite advancements in the field, there is still a high unmet need for technologies to accurately and reliably grade liver steatosis and stage liver fibrosis for applications related to patient identification and monitoring response to therapeutic intervention.
The association between hepatic steatosis and fibrosis progression underscores the need to have accurate and reliable noninvasive tools to aid in the assessment and monitoring of both liver steatosis and fibrosis.
The combination of 2 US (ultrasound) biomarkers that quantify liver tissue fat and stiffness (UDFF and pSWE) may aid clinicians in streamlining patient care pathways and potentially avoid unwanted and invasive medical intervention.
Přehled studie
Postavení
Detailní popis
This study will consist of 3 phases:
- Technologist Training: Pre-study training will be conducted for all US (ultrasound) and MRI technologists to ensure standardized image acquisition across study sites.
- A Pilot Study will be conducted in healthy adult participants to qualify imaging centers to participate in the Main Study.
- The Main Study will be conducted in adult participants suspected of MASH (metabolic dysfunction-steatohepatitis) (with moderate to advanced fibrosis consistent with F2-F3 to evaluate the diagnostic performance of the combination of 2 US (ultrasound) biomarkers (UDFF and pSWE) for determining MRI-defined eligibility for resmetirom treatment and for monitoring treatment response over time .
A Pilot Study will be conducted before the Main Study to verify image acquisition quality and data completeness, and to assess repeatability (US) and reproducibility (US and MRI). The Pilot Study will include 24 adult participants (n=8 participants/site across 3 imaging centers).
Each participant in the pilot study will undergo 4 US (ultrasound) scans (2 scans each by 2 Certified US Technologists).
All US scans will be performed on SIEMENS ACUSON Sequoia systems using the 5C1 transducer and the same software version throughout the study. Repeated US scans will be separated by ≥5 minutes, with participants repositioned between scans by the Certified US Technologists.
Each participant in the pilot study will also undergo 2 MRI scans (1 scan each by 2 Certified MRI Technologists):
MR scans will be performed using either the SIEMENS MAGNETOM Skyra 3T or GE SIGNA PIONEER 3T, depending on scheduling and site availability. The MR scanner will be running the same software version throughout the study.
Data from participants in the Pilot Study will not be included in the analysis of the Main Study.
Data Quality Verification :
All pilot data will be reviewed by Siemens to verify image acquisition quality, completeness, and adherence to the imaging protocol.
Repeatability and reproducibility will be evaluated in the Pilot Study.
Main Study
Participants will be recruited from clinical practices in the Houston, Texas area by hepatologists, gastroenterologists, and other referring clinicians. US (ultrasound) and MRI examinations will be performed across 3 Sponsor imaging centers in the Houston area. All participants will undergo Baseline US (ultrasound) biomarkers (UDFF, pSWE) and MRI biomarkers (MRI-PDFF, MRE) on the same day.
Blinding
- Referring physicians will be blinded to US (ultrasound) (UDFF and pSWE) results, and thus decisions to prescribe resmetirom will be made based solely on MRI biomarkers (ie, MRI-PDFF and MRE) and clinical assessment.
- US (ultrasound) operators will be blinded to results from MRI biomarkers (MRI-PDFF and MRE).
- MRI operators will be blinded to results from US (ultrasound) biomarkers (UDFF and pSWE).
Duration of Study Participation
- Pilot Study: 1 day, in addition to the Screening Visit
- Main Study :
- Participants NOT treated with resmetirom: Screening(consenting)and day 1 baseline MRI and US(2 visits total);
- Participants treated with resmetirom (prescribed by their referring physician based on Baseline MRI results and clinical assessment): Screening (consenting), day 1 baseline MRI and US then at months 6, 12 and 24 (5 visits total).
Study Assessments
- Record demographics
- Record medication history since last visit
- Record laboratory test results since last visit
- Perform US (ultrasound)
- Perform MRI
- Record/report SAEs
Typ studie
Zápis (Odhadovaný)
Kontakty a umístění
Studijní kontakt
- Jméno: Senior Vice President of Research
- Telefonní číslo: +1 562-981-6101
- E-mail: Kristi.Maya@radnet.com
Studijní záloha kontaktů
- Jméno: Clinical Research Regulatory Specialist
- Telefonní číslo: +1 562-206-7701
- E-mail: Jacqueline.Bral@radnet.com
Studijní místa
-
-
Texas
-
Houston, Texas, Spojené státy, 77055
- HMI/Campbell
-
Kontakt:
- Senior Vice President of Research
- Telefonní číslo: +1 562-981-6101
- E-mail: Kristi.Maya@radnet.com
-
Kontakt:
- Clinical Research Regulatory Specialist
- Telefonní číslo: +1 562-206-7701
- E-mail: Jacqueline.Bral@radnet.com
-
Vrchní vyšetřovatel:
- Randall Stenoien, MD
-
Houston, Texas, Spojené státy, 77079
- HMI/Energy Corridor
-
Kontakt:
- Senior Vice President of Research
- Telefonní číslo: +1 562-981-6101
- E-mail: Kristi.Maya@radnet.com
-
Kontakt:
- Clinical Research Regulatory Specialist
- Telefonní číslo: +1 562-206-7701
- E-mail: Jacqueline.Bral@radnet.com
-
Vrchní vyšetřovatel:
- Randall Stenoien, MD
-
Pearland, Texas, Spojené státy, 77581
- HMI/Pearland
-
Kontakt:
- Senior Vice President of Research
- Telefonní číslo: +1 562-981-6101
- E-mail: Kristi.Maya@radnet.com
-
Kontakt:
- Clinical Research Regulatory Specialist
- Telefonní číslo: +1 562-206-7701
- E-mail: Jacqueline.Bral@radnet.com
-
Vrchní vyšetřovatel:
- Randall Stenoien, MD
-
-
Kritéria účasti
Kritéria způsobilosti
Věk způsobilý ke studiu
Přijímá zdravé dobrovolníky
Pohlaví způsobilá ke studiu
Metoda odběru vzorků
Studijní populace
Participants must be fully informed of the potential benefits of approved products and make an informed decision that they prefer to participate in a clinical study. Regulatory, ethical, and study oversight considerations are provided in the protocol.
Participants will be recruited from clinical practices in the Houston, Texas area by hepatologists, gastroenterologists, and other referring clinicians.
- Participants in the Pilot Study will be healthy adult males or females, age ≥18 years.
- Participants in the Main Study will be adult males or females, age ≥18 years, suspected of MASH with moderate to advanced fibrosis consistent with F2-F3.
Participants will be eligible if they meet ALL inclusion criteria and NONE of the exclusion criteria at Screening.
Popis
Enrollment Criteria
Participants will be recruited from clinical practices in the Houston, Texas area by hepatologists, gastroenterologists, and other referring clinicians.
Inclusion Criteria (Pilot Study):
- Participants must meet the following criteria:
- Healthy adults (≥18 years) with no known liver diseases
Inclusion Criteria (Main Study):
- Participants must meet the following criteria:
- Adults (≥18 years) suspected of MASH with moderate to advanced fibrosis consistent with F2-F3 with no other known liver disease
Exclusion Criteria (Pilot Study, Main Study):
Participants meeting ANY of the following criteria will be excluded:
- Use of steatogenic or hepatotoxic medications (eg, corticosteroids such as prednisone, amiodarone, methotrexate, tamoxifen)
- Contraindications to MRI
- Pregnancy
Studijní plán
Jak je studie koncipována?
Detaily designu
- Observační modely: COHORT
- Časové perspektivy: PROSPECTIVE
Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
Diagnostic performance of UDFF (ultrasound-derived fat fraction)
Časové okno: Enrollment Day 1 Baseline
|
Ultrasound criteria associated with elevated liver fat at baseline: UDFF ≥8% |
Enrollment Day 1 Baseline
|
|
Diagnostic performance of Ultrasound pSWE (point shear wave elastography)
Časové okno: Enrollment Day 1 Baseline
|
Ultrasound criteria consistent with MASH F2-F3 fibrosis at baseline: pSWE ≥7 and <17 kPa |
Enrollment Day 1 Baseline
|
Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
The accuracy of the Ultrasound biomarker pSWE (point shear wave elastography) for monitoring resmetirom treatment response over time.
Časové okno: 6 months to 24 months of follow-up period
|
Percent changes in Ultrasound pSWE from baseline to follow-up period are tested for statistical equivalence. |
6 months to 24 months of follow-up period
|
|
The accuracy of the Ultrasound biomarker UDFF (ultrasound-derived fat fraction) for monitoring resmetirom treatment response over time.
Časové okno: 6 months to 24 months of follow-up period
|
Percent changes in UDFF from baseline to follow-up period are tested for statistical equivalence |
6 months to 24 months of follow-up period
|
|
Corresponding percent changes in MRI-PDFF (proton density fat fraction) from baseline to follow- up period are tested for statistical equivalence
Časové okno: 6 months to 24 months follow-up period
|
MR criteria associated with elevated liver fat at baseline: PDFF ≥8% |
6 months to 24 months follow-up period
|
|
Corresponding percent changes in MRE (magnetic resonance elastography) from baseline to followup period are tested for statistical equivalence
Časové okno: 6 months to 24 months follow-up period
|
MR criteria consistent with MASH F2-F3 fibrosis at baseline: MRE ≥3.3 and <5 kPa |
6 months to 24 months follow-up period
|
|
Correlation between percent changes in imaging biomarkers for monitoring resmetirom treatment response over time.
Časové okno: 6 months to 24 months follow-up period
|
Percent changes in UDFF and MRI-PDFF values from baseline to follow-up period and Percent changes in pSWE and MRE values from baseline to follow-up period. |
6 months to 24 months follow-up period
|
Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
|
To evaluate factors influencing imaging biomarkers MRI-PDFF, MRE, UDFF and pSWE.
Časové okno: Enrollment Day 1 Baseline to 24 months follow-up period
|
• Assessment of the influence of GLP-1 therapy use using a subgroup analysis. |
Enrollment Day 1 Baseline to 24 months follow-up period
|
|
To evaluate factors influencing imaging biomarkers MRI-PDFF, MRE, UDFF and pSWE.
Časové okno: Enrollment Day 1 Baseline to 24 months followup period
|
• Assessment of the influence of weight change using a subgroup analysis. |
Enrollment Day 1 Baseline to 24 months followup period
|
|
To evaluate factors influencing imaging biomarkers MRI-PDFF, MRE, UDFF and pSWE.
Časové okno: Enrollment Day 1 Baseline to 24 months follow-up period
|
• Assessment of the association of BMI |
Enrollment Day 1 Baseline to 24 months follow-up period
|
|
To evaluate factors influencing imaging biomarkers MRI-PDFF, MRE, UDFF and pSWE.
Časové okno: Enrollment Day 1 Baseline to 24 months follow-up period.
|
• Assessment of the association of MR-R2 (speed of signal delay) |
Enrollment Day 1 Baseline to 24 months follow-up period.
|
|
To evaluate factors influencing imaging biomarkers MRI-PDFF, MRE, UDFF and pSWE.
Časové okno: Enrollment Day 1 Baseline to 24 months follow-up period
|
Assessment of association of laboratory findings |
Enrollment Day 1 Baseline to 24 months follow-up period
|
Spolupracovníci a vyšetřovatelé
Sponzor
Vyšetřovatelé
- Vrchní vyšetřovatel: Randall Stenoien, MD, RadNet Research
Termíny studijních záznamů
Hlavní termíny studia
Začátek studia (Odhadovaný)
Primární dokončení (Odhadovaný)
Dokončení studie (Odhadovaný)
Termíny zápisu do studia
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První předloženo, které splnilo kritéria kontroly kvality
První zveřejněno (Aktuální)
Aktualizace studijních záznamů
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Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
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Klíčová slova
Další relevantní podmínky MeSH
Další identifikační čísla studie
- MSR-001
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