Phase 2a Study of HPG1860 in Subjects With NASH

This is a Phase 2a, randomized, double-blind, placebo-controlled, parallel group, multiple arm, multicenter study of 3 different doses of HPG1860 versus placebo in subjects with biopsy-confirmed or phenotypic NASH. Screening will occur up to 5 weeks prior to randomization; all eligible subjects will have baseline hepatic imaging during Screening, prior to randomization. Approximately 80 eligible subjects will be randomized 1:1:1:1 on Day 1/Week 0 (T1) to receive either HPG1860 3 mg (n = 20), or 5 mg (n = 20), or 8 mg (n = 20), or placebo (n = 20) for 12 weeks. Following a preplanned interim analysis, a dose cohort may be dropped and/or added.

Inclusion criteria

• Provision of written informed consent prior to any study-specific procedure.
• Males and females between 18 and 75 years of age
• Nonpregnant, nonlactating women.
• Male subjects must agree to utilize a highly effective method of contraception.
• Body mass index (BMI) of ≥25 kg/m2 at Screening.
• Non-cirrhotic NASH subjects.
• NASH subjects with hepatic fat assessed by a central reader
• Willing and able to adhere to study restrictions and agree to comply with study protocol.

Exclusion criteria

• Pregnant or lactating females
• Current significant alcohol consumption
• Elevated LDL-C with stable dose of statin an or PCSK9 inhibitor
• Renal dysfunction or nephritic syndrome or a history of nephritis
• Recent infarction, unstable angina leading to hospitalization, uncontrolled, symptomatic cardiac arrhythmia
• Uncontrolled hypertension
• Type 1 diabetes or uncontrolled T2DM
• Uncontrolled hypothyroidism
• Liver transplant and/or other significant liver disease or dysfunction
• HIV antibody positive
• Known hypersensitivity or formulation excipient
• Gastrointestinal conditions or procedures that may affect drug absorption
• Hematologic or coagulation disorders
• Unstable weight within the last 3 months
• Active malignancy
• Unexplained creatine kinase (CK) >3 × ULN
• Blood donation, blood transfusion
• Unable to undergo or contraindication to MRI procedure
• A medical or situational finding that in the investigator's opinion may compromise the subject's safety or ability to complete the study.