Resmetirom treatment for adults with MASLD and HIV

A Randomized, Double-Blind, Placebo-Controlled, Multicenter Trial of Resmetirom for the Treatment of Metabolic Dysfunction- Associated Steatotic Liver Disease (MASLD) in People Living With Human Immunodeficiency Virus (HIV)

This study will test whether taking resmetirom daily for 24 weeks lowers liver fat in adults who have MASLD and well-controlled HIV on antiretroviral therapy.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 120 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Indiana University (other)
• Locations: 10 sites (Birmingham, Alabama and 9 other locations)
• Trial ID: NCT07143968 on ClinicalTrials.gov

What this trial studies

This randomized, placebo-controlled Phase 2 trial enrolls adults with MASLD and documented HIV who are on stable antiretroviral therapy. Participants will be assigned to resmetirom or a matching placebo and take the study drug daily for 24 weeks, with MRI-PDFF scans before treatment and at week 24 to measure liver fat. Safety and adherence are monitored with three scheduled clinic visits, three phone calls, and routine bloodwork; eligibility requires hepatic fat ≥8% by MRI-PDFF and HIV-1 RNA <200 copies/mL. The trial is being run at three U.S. academic centers and excludes participants with recent significant alcohol use.

Who should consider this trial

Good fit: Adults aged 18 or older with diagnosed MASLD (hepatic fat ≥8% by MRI-PDFF), documented HIV with HIV-1 RNA <200 copies/mL on a stable ART regimen, and no recent significant alcohol use are ideal candidates.

Not a fit: People with uncontrolled HIV, recent heavy alcohol use, advanced or decompensated liver disease, or unstable ART are unlikely to qualify or benefit from this study.

Why it matters

Potential benefit: If successful, resmetirom could reduce liver fat and improve liver-related outcomes for people with MASLD who also have HIV.

How similar studies have performed: Previous resmetirom trials in people without HIV have shown reductions in liver fat and improvements in liver biomarkers, but its effects specifically in people with HIV have not been previously established.

Eligibility criteria

Inclusion Criteria:

1. Adults (≥18 years of age) with documented HIV.
2. Documented diagnosis of MASLD established by imaging (ultrasound, CT scan or MRI) or vibration-controlled transient elastography (VCTE) or liver biopsy within 12 months before screening.
3. Hepatic fat fraction ≥8% by MRI-PDFF.
4. Liver stiffness by VCTE ≥8 kPa and CAP≥263 dB/m
5. HIV-1 RNA \<200 copies/mL for ≥6 months on antiretroviral therapy (ART) (must have screening HIV-1 RNA value and one clinical care value within 6 months prior to screening and up to the randomization that meet the criteria).
6. Stable ART regimen for ≥3 months prior to screening and stable up to the randomization and no active plans to change ART while on study.
7. Willingness to participate in the study.

Exclusion Criteria:

1. History of significant alcohol consumption (defined as \>2 drinks/day on average for men, \>1 drinks/day on average for women) for at least 3 consecutive months (12 consecutive weeks) within 5 year before screening
2. History of other acute or chronic liver disease, including, but not limited to autoimmune, primary biliary cholangitis, Wilson's disease, alpha 1 antitrypsin deficiency, hemochromatosis, hepatitis B virus (HBV), and ongoing or recent (within the past 3 years) hepatitis C RNA positivity.
3. History of liver transplant.
4. Liver biopsy or radiologic imaging consistent with the clinical presence of cirrhosis or portal hypertension at screening.
5. Participants whose Visit 2 ALT, AST, or alkaline phosphatase (ALP) values exceed their Visit 1 values by more than 50%.
6. Inability to undergo MRI testing
7. Uncontrolled T2DM defined as glycated hemoglobin (HbA1c) \>9.5% at screening.
8. Any of the following laboratory values at screening:

   1. ALT or AST \>250 U/L.
   2. Total bilirubin (TBL) \>1.5 mg/dL and direct bilirubin \> 0.5 mg/dL (unless due to Gilbert's disease or atazanavir use, per the opinion of the site investigator).
   3. Platelet count \<150,000/mm3.
   4. Estimated glomerular filtration rate (e-GFR) \<60 mL/min/1.73m2 using the chronic kidney disease-epidemiology collaboration (CKD-EPI) equation
   5. International normalized ratio (INR) \>1.3.
   6. Albumin \< 3.6 g/dL
9. Liver stiffness measurement (LSM) by VCTE \> 20 kPa
10. Further exclusion criteria apply

Where this trial is running

Birmingham, Alabama and 9 other locations

• University of Alabama Birmingham — Birmingham, Alabama, United States (NOT_YET_RECRUITING)
• UC San Diego Altman Clinical and Translational Research Institute — La Jolla, California, United States (NOT_YET_RECRUITING)
• University of California, San Francisco — San Francisco, California, United States (NOT_YET_RECRUITING)
• Atlantic Clinical Research Institute — West Palm Beach, Florida, United States (NOT_YET_RECRUITING)
• Indiana University — Indianapolis, Indiana, United States (RECRUITING)
• Johns Hopkins University — Baltimore, Maryland, United States (NOT_YET_RECRUITING)
• Mt Sinai Health System — New York, New York, United States (NOT_YET_RECRUITING)
• Duke University Medical Center — Durham, North Carolina, United States (NOT_YET_RECRUITING)
• UT Health Houston — Houston, Texas, United States (NOT_YET_RECRUITING)
• Virginia Commonwealth University — Richmond, Virginia, United States (NOT_YET_RECRUITING)

Study contacts

• Study coordinator: Holly Crandall, BSN

Conditions: MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, HIV