A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)

A Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)

A Phase 2a, Randomized, Blinded, Placebo-controlled Study of BOS-580 in Obese Subjects at Risk for, or With Biopsy-confirmed, Nonalcoholic Steatohepatitis (NASH)

This is a safety study to evaluate BOS-580 administered subcutaneously over 12 weeks in Part A or 24 weeks in Part B.

Part A and Part B: Number of participants with treatment-emergent adverse events (TEAE) and treatment-emergent serious adverse events (TESAE)

Part A and Part B: Changes from Baseline to Week 12 (Day 85) in systolic and diastolic blood pressure (BP)

Part A and Part B: Number of participants with Grade 3 and Grade 4 laboratory abnormalities at Week 12 (Day 85)

Part B only: Changes from Baseline to Week 24 (Day 169) and Week 28 (Day 197) in systolic and diastolic BP

Part B only: Number of participants with Grade 3 and Grade 4 laboratory abnormalities at Week 24 (Day 169) and Week 28 (Day 197)

Pre-dose at Days 15, 29, 43, 57, 71, 85 and 113 (End of study/Early termination) for bi-weekly schedule; pre-dose on Days 29, 57, 85 and 113 (End of study/Early termination) for the monthly schedule

Part B Only: Area under the serum concentration-time curve (AUC) for BOS-580 for one dosing interval at steady state

Inclusion Criteria: Participant is either male or female and 18 to 75 years of age inclusive, at the time of signing the informed consent Obese participants with body mass index (BMI) of ≥ 27 kg/m^2 Hepatic fat fraction (HFF) measured by magnetic resonance imaging derived proton density fat fraction (MRI-PDFF) ≥8% Liver fibrosis assessment based on a vibration controlled transient elastography (VCTE) liver stiffness measurement (LSM) score of 7.0 to 9.9 kPa (Part A only) inclusive or 7.0 to 20.0 kPa (Part B only) inclusive and Liver injury assessment measured by aspartate aminotransferase (AST) >25U/L. A qualifying historical biopsy (confirmed eligibility based on the central pathology read) supersedes the LSM and controlled attenuation parameter (CAP) score criteria. Histopathologically confirmed F2 or F3 stage NASH on a diagnostic liver biopsy performed during Screening or within 6 months prior to the first day of dosing for historical biopsies (Part B only). Exclusion Criteria: Documented clinical, laboratory or radiologic evidence of cirrhosis (compensated or decompensated) Triglycerides ≥ 500 mg/dL Change in body weight (more than 5% self-reported OR 5 kg self-reported change during the previous 3 months from Screening, whichever is smaller) History of type 1 diabetes, diabetic ketoacidosis, or positive glutamic acid decarboxylase (GAD) auto-antibodies (latent autoimmune diabetes in adults) Hemoglobin A1c > 9.5% Subjects with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis).