GILEAD NASH Trial
Objective: To evaluate the safety and tolerability of GS-0976 in subjects with nonalcoholic steatohepatitis (NASH) as assessed by magnetic resonance imaging proton-density fat fraction (MRI-PDFF) and magnetic resonance elastography (MRE).
GS-0796 is a small molecule allosteric inhibitor that acts at the protein-protein homodimer interface of acetyl Co-A carboxylases ACC1 and ACC2, to prevent dimerization. ACC1 catalyzes the first step of the de novo lipogenesis (DNL) by converting acetyl CoA to malonyl CoA while ACC2 regulates the entry of fatty acids into the mitochondria where beta oxidation can occur. Therefore, inhibition of ACC1 and ACC2 will reduce DNL and increase fatty acid beta oxidation.
Participation in the study can last up to 21 weeks, including a 4-week Screening period, a 12-week treatment period during which study drugs will be administered, and a 4-week follow-up period. Subjects meeting the study’s entry criteria will be randomized assigned in a 2:2:1 ratio to 3 treatment groups, as follows:
- A clinical diagnosis of nonalcoholic fatty liver disease (NAFLD) with imaging documenting fatty liver within two years prior to screening. If necessary an ultrasound may be performed during screening to confirm NAFLD.
- Screening MR-PDFF with ≥ 10 % steatosis.
- Screening MRE with liver stiffness ≥ 2.90 kPa.
Please note: Historical biopsies within 1 year can be used for study entry. All patients will receive study drug as described above.