a study of bos-580 in obese subjects at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (nash) with an extension

Conditions: Nonalcoholic Steatohepatitis (NASH)

Summary: this is a randomized, blinded, placebo-controlled study of efimosfermin in obese participants at risk for, or with biopsy-confirmed, nonalcoholic steatohepatitis (nash), with a single arm open-label extension. it includes parts a, b, c and d.


Eligibility criteria:
inclusion criteria (part a and part b): * 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, controlled attenuation parameter (cap) score criteria and ast 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). * history or presence of at least 2 of 4 components of metabolic syndrome: obesity/overweight, dyslipidemia (high triglycerides and/or low high density lipoprotein \[hdl\]), type 2 diabetes with elevated glycated hemoglobin (hba1c), and hypertension. inclusion criteria (part c): * participant must have completed the part b of the study. * participant willing to undergo liver biopsy at week 56 * nash f stage \<f4 at 24 week assessment in part b inclusion criteria (part d): * bmi of ≥ 25 kg/m\^2 * liver fibrosis based on assessments taken during screening visit * participant should be willing and able to undergo liver biopsy during screening (if a historical biopsy within 12 months prior to screening is not available) and per protocol as judged by the investigator. * other inclusion criteria may apply exclusion criteria (part a and part b): * 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% * participants with a condition that requires substantial anticoagulant medication may not be eligible for the study enrollment (e.g., deep vein thrombosis). exclusion criteria (part c): • participants that received their 24 week dose in part b \> 10 weeks prior to enrollment into part c exclusion criteria (part d): * other causes of chronic liver disease * documented evidence or history of decompensated liver cirrhosis. * history of type 1 diabetes or poorly controlled type 2 diabetes. * history of malignancy. * use of other investigational drugs. * other exclusion criteria may apply

Keywords: bos-580 safety tolerability pharmacokinetics efimosfermin