Study of ADI-PEG 20 Versus Placebo in Subjects With NASH

Launched by POLARIS GROUP · Apr 24, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a medication called ADI-PEG 20 to see how well it works and how safe it is for people with a liver condition known as Nonalcoholic Steatohepatitis (NASH). NASH is a type of liver disease that can cause inflammation and damage to the liver without the influence of alcohol. The trial is currently looking for participants aged 18 to 80 who have been diagnosed with NASH through a liver biopsy and meet specific criteria, such as having a certain amount of liver fat and a body mass index (BMI) over 25.

If you decide to participate, you'll be randomly assigned to receive either the ADI-PEG 20 medication or a placebo (a treatment that has no active ingredients) for a certain period. Throughout the trial, you'll have regular check-ups and tests to monitor your health. It’s important to be aware that there are some criteria that might exclude you from joining, such as having certain other liver conditions, severe diabetes, or recent significant weight changes. Overall, this study aims to find a better treatment option for people living with NASH, and your participation could help advance medical knowledge in this area.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Males and non-lactating, pregnancy test negative females between 18 - 80 years of age with biopsy proven F1 - F3 NASH. Limit F1 fibrosis to ≤ 20% of total subject population.
• • 2. Willingness to use appropriate contraceptive measures though out study treatment and for 90 days thereafter (see Appendix A).
• • 3. Body mass index (BMI) \> 25 kg/m2
• • 4. Must have confirmation of ≥ 10% liver fat content on MRI-PDFF at screening.
• 5. Biopsy-proven NASH. Must have had a liver biopsy within 4 weeks of randomization with fibrosis stage 1 to 3 and a non-alcoholic fatty liver disease (NAFLD) activity score (NAS) of ≥ 4 with at least a score of 1 in each of the following NAS components:
• • 1. Steatosis (scored 0 to 3),
• • 2. Ballooning degeneration (scored 0 to 2), and
• • 3. Lobular inflammation (scored 0 to 3).
• • 6. Must have no evidence of worsening of ALT and AST (within 50%) measurements at the screening (-4 weeks) and pre-baseline (-2 weeks) visits.
• 7. Screening laboratory parameters, as determined by the central laboratory:
• • 1. Estimated glomerular filtration rate (eGFR) ≥ 60 mL/min, as calculated by the Cockcroft- Gault equation;
• • 2. HbA1c ≤ 9.5% (or serum fructosamine ≤ 381 µmol if HbA1c is unable to be resulted);
• • 3. Hemoglobin ≥ 11 g/dL;
• • 4. INR ≤ 1.3, unless due to therapeutic anticoagulation;
• • 5. Direct bilirubin ≤ 0.5 mg/dL;
• • 6. Total bilirubin ≤ 1.3 x upper limit of normal (ULN), unless due to an alternate etiology such as Gilbert's syndrome or hemolytic anemia;
• • 7. Creatinine kinase \< 3 x ULN;
• • 8. Platelet count ≥ 150,000/µL;
• • 9. Serum triglyceride level ≤ 500 mg/dL;
• • 10. ALT \< 5 x ULN;
• • 11. AST \< 5 x ULN;
• • 12. ALP \< 2 x ULN.
• • 8. FibroScan® measurement \> 7.0 kPa
• • 9. Subjects on non-insulin dependent diabetic, weight loss, or lipid-modifying medication(s) must be on stable dose(s) for at least 3 months prior to the diagnostic liver biopsy through randomization.
• Exclusion Criteria:
• • 1. Weight gain or loss \> 5% in the 3 months prior to randomization or \> 10% in the 6 months prior to screening.
• • 2. Type 1 and insulin-dependent Type 2 diabetes.
• • 3. Presence of cirrhosis on liver biopsy (stage 4 fibrosis).
• • 4. Poorly controlled hypertension (blood pressure \[BP\] \> 160/100 mmHg).
• • 5. Prior history of decompensated liver disease including ascites, hepatic encephalopathy (HE), or variceal bleeding.
• • 6. Chronic hepatitis B virus (HBV) infection (hepatitis B surface antigen \[HBsAg\] positive).
• • 7. Chronic hepatitis C virus (HCV) infection (HCV antibody \[Ab\] and HCV ribonucleic acid \[RNA\] positive). Subjects cured of HCV infection less than 2 years prior (based on date of RNA polymerase chain reaction \[PCR\] negative confirmation following conclusion of treatment) to the screening visit are not eligible.
• • 8. Prior or planned (during the study period) bariatric surgery (e.g., gastroplasty, roux-en-Y gastric bypass), surgery reversal or removal of intragastric balloon \> 2 years prior to enrollment would be eligible.
• • 9. Other causes of liver disease based on medical history and/or centralized review of liver histology, including but not limited to: alcoholic liver disease, autoimmune disorders (e.g., primary biliary cholangitis \[PBC\], primary sclerosing cholangitis \[PSC\], autoimmune hepatitis), drug-induced hepatotoxicity, Wilson disease, clinically significant iron overload, or alpha-1-antitrypsin deficiency requiring treatment.
• • 10. History of liver transplantation.
• • 11. Current or prior history of hepatocellular carcinoma (HCC).
• • 12. Alcohol intake above an average limit of 2 drinks per day for women and 3 drinks per day for men.
• • 13. Human immunodeficiency virus (HIV) infection.
• • 14. Unstable cardiovascular disease in the 6 months prior to screening.
• • 15. Life expectancy less than 2 years.
• • 16. Use of any investigational medication within 30 days or within 5 half-lives of the investigational medication, whichever is longer, prior to screening and throughout the study is prohibited.
• • 17. Subjects with a history of (12 months prior to screening) or current use of prescription drugs associated with liver steatosis (e.g. methotrexate, amiodarone, high-dose estrogen, tamoxifen, systemic steroids, anabolic steroids, valproic acid) should be excluded.