Safety, Tolerability, and Efficacy of Saroglitazar Mg 4 mg in Liver Transplant Recipients With Nonalcoholic Fatty Liver Disease (NAFLD)

This is a phase 2A, single center, open-label, single-arm, 24-week study to evaluate the safety, tolerability and efficacy of Saroglitazar Magnesium 4 mg in liver transplant recipients with NAFLD.

The study will be conducted over a period of up to 33 weeks and will include 5 weeks screening, a 24 week treatment period and 4 week follow-up period. The primary end point of the study is to assess the safety of Saroglitazar Magnesium 4 mg in liver transplant recipients with NAFLD over 24 weeks of treatment.

Inclusion criteria

• Able and willing to give written informed consent.
• Males or females, 18 to 75 years of age.
• Patients who are at least 6 months post-transplant for nonalcoholic steatohepatitis (NASH) or cryptogenic cirrhosis thought to be secondary to NASH are eligible for enrolment.
• The presence of NAFLD determined by Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) prior to enrollment.
• Patients with ≤20% variance in the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin between Visit 1 and Visit 1.1.
• History of medical compliance with immunosuppression.
• Female subjects of non-child bearing potential or on highly effective contraception. For male subjects with female partners of childbearing potential, willing to follow highly effective contraception measures during the study, either by the male participant or his female partner or both.

Exclusion criteria

• Pregnant or lactating females.
• Patient with abnormal transaminases due to secondary intercurrent illness.
• Patients with bile duct strictures.
• Other causes of chronic liver disease after liver transplantation including autoimmune, viral, and alcoholic liver disease.
• Graft cirrhosis as defined by:

• Cirrhosis on historical liver biopsy.
• Evidence of cirrhosis on imaging including portal venous collaterals.
• Prior history of decompensated liver disease including ascites, hepatic encephalopathy or variceal bleeding.
• Evidence of esophageal varices on prior endoscopy.
• Body mass index (BMI) <18 kg/m².
• Subjects with change in body weight >5% in the 3 months prior to enrollment.
• Subjects requiring corticosteroid or anticoagulation therapy.
• History of myopathies or evidence of active muscle diseases.
• Unstable cardiovascular disease.
• History of bladder disease and/or hematuria or has current hematuria unless due to a urinary tract infection.
• Active malignancy post-liver transplantation.
• History of malignancy in the past 5 years and/or active neoplasm.
• History of chronic rejection of liver transplant graft.
• Acute cellular rejection of liver transplant graft within the past 6 months.
• Evidence of Acute cellular rejection (ACR) or chronic rejection (CR) or alternative etiologies to NAFLD.
• Poorly controlled diabetes as defined by an HbA1c >8.5% within the past 6 months.
• History of excessive alcohol intake.
• Subject tests positive for a urine drug screen.
• Subject has a history of chronic (uncontrolled) pain.