Leronlimab (PRO 140) in Patients With Nonalcoholic Steatohepatitis

Inclusion Criteria: Subjects are required to meet ALL of the following criteria for enrollment into the study:

• Subject is a male or female between 18 to 75 years of age inclusive.
• Evidence of nonalcoholic steatohepatitis (NASH) based on one of the following criteria:
• Criteria 1: Histologically-confirmed diagnosis of NASH on a liver biopsy, or
• Criteria 2: FibroScan or Shearwave US during screening (or within 6 months before screening) shows kPa ≥7 but ULN
• Screening Liver enzymes (AST, ALT, and ALK PHOS) < 5 x ULN.
• Total Bilirubin ≤ 1.3 mg/dL (except if Gilbert's Disease)
• Platelet count ≥ 150,000/mm3
• International normalized ratio (INR) < 1.3
• Estimated Glomerular Filtration Rate (eGFR) ≥ 60/mL/min
• Glycosylated hemoglobin (HbA1c) < 9%.
• Thyroid-Stimulating Hormone (TSH) within normal reference range. Note: Any subject with a non-clinically significant TSH value outside of the normal range may be enrolled if their T3 and free T4 values are within the normal range.
• Subjects with pre-diabetes or type 2 diabetes will be allowed to participate if the following criteria is met:
• Subjects who are taking anti-diabetic medications should be on a stable dose for a period of at least 3 months prior to Screening and do not anticipate clinically significant dose adjustments during the course of study.
• Subjects must be on a stable diet/lifestyle regimen for at least 3 months prior to screening and do not anticipate a clinically significant change during the course of study.
• Subjects who are taking Vitamin E should be on a stable dose of Vitamin E (if ≥ 400 IU) for a period of at least 4 weeks prior to Screening and do not anticipate dose adjustments for the duration of the study.
• Both male and female patients and their partners of childbearing potential must agree to use two medically accepted methods of contraception (e.g., barrier contraceptives [male condom, female condom, or diaphragm with a spermicidal gel], hormonal contraceptives [implants, injectables, combination oral contraceptives, transdermal patches, or contraceptive rings], or one of the following methods of birth control (intrauterine devices, tubal sterilization or vasectomy) or must practice complete abstinence from intercourse of reproductive potential from study entry to 6 months after the last day of treatment (excluding women who are not of childbearing potential and men who have been sterilized).
• Females of child-bearing potential must have a negative serum pregnancy test at Screening Visit and negative urine pregnancy test prior to receiving the first dose of study drug; and Male participants must agree to use contraception and refrain from donating sperm for at least 90 days after the last dose of study intervention.
• Subject is willing and able to give informed consent prior to any study specific procedures being performed.
• Subject is willing and able to comply with scheduled visits, drug administration plan, laboratory tests, other study procedures and study restrictions

Exclusion Criteria: Subjects meeting ANY of the following criteria will be excluded from enrollment:

• Any concurrent clinically significant liver disease with an etiology other than NASH including autoimmune hepatitis, alcoholic hepatitis, hypoxic/ischemic hepatopathy, and biliary tract disease.
• History of alcohol consumption greater than 21/units/week (for males) and 14/units/week (for females) within the last 2 years prior to screening.

Note: Use of online unit calculator for alcohol consumption is recommended (e.g., https://alcoholchange.org.uk/alcohol-facts/interactive-tools/unit-calculator)

• Any drug-induced steatohepatitis secondary to amiodarone, corticosteroids, estrogens, methotrexate, tetracycline, or other medications known to cause hepatic steatosis.
• Undergone major surgery, including liver surgery, within 6 months prior to screening deemed clinically significant by the investigator.
• Prior or pending liver transplanta