Use of F-652 in Patients With Alcoholic Hepatitis

IL-22 is a member of the IL-10 family of cytokines which control bacterial infection, homeostasis, and tissue repair. IL-22 may be used to treat patients with ALD because of its antioxidant, anti-apoptotic, anti-steatotic, anti-microbial, and proliferative effect that have been demonstrated in various experimental systems.

The sponsor has developed F-652, a recombinant human IL-22 IgG2 Fc fusion protein produced in serum-free culture of Chinese Hamster Ovary (CHO) cells. F-652 is able to protect tissue from damage and enhance tissue repair during the inflammation process and infection by activation of STAT3 mediated by the interleukin-22 receptor subunit 1 (IL-22R1) expressed on epithelial cells such as hepatocytes.

3.1 Inclusion Criteria

To participate in this study, patients must meet all of the following criteria:

• Able to provide written informed consent (either from patient or patient's legally acceptable representative)
• Male or female patients 21 years of age or older
• Patients with alcoholic hepatitis defined as:

• History of heavy alcohol abuse use: >40 g/day in females and >60 g/day in males for a minimum period of 6 months
• Consumed alcohol within 6 weeks of entry into the study
• Serum bilirubin > 3mg/dL AND AST >ALT, but less than 500 U/L
• MELD score between 11-28
• Liver biopsy will be carried out to confirm diagnosis in all patients except those who meet criteria a-c and in whom other causes of liver disease have been excluded (viral, drug, autoimmune etc).
• Women of child-bearing potential must utilize appropriate birth control. *Patients on steroids and/or pentoxifylline will not be excluded from the study.

Exclusion criteria

• Other or concomitant cause of liver disease as a result of:

• Autoimmune liver disease
• Wilson disease
• Vascular liver disease
• Drug induced liver disease Note: Concurrent viral hepatitis is not excluded.
• Co-infection with human immunodeficiency virus (HIV)
• Any active malignancies other than curatively treated skin cancer (basal cell or squamous cell carcinomas) or any other malignancy diagnosed within the last five years.
• Active tuberculosis on chest x-ray at study entry
• Significant systemic or major illness other than liver disease, including coronary artery disease, cerebrovascular disease, pulmonary disease, renal failure, serious psychiatric disease, that, in the opinion of the Investigator would preclude the patient from participating in and completing the study
• Patients requiring the use of vasopressors or inotropic support
• Liver biopsy, if carried out, showing findings not compatible with alcoholic hepatitis
• Any patient that has received any investigational drug or device within 30 days of dosing or who is scheduled to receive another investigational drug or device in the course of the study Note: Investigational drug includes any drug that is used off-label.
• If female, known pregnancy, or has a positive urine or serum pregnancy test, or lactating/breastfeeding
• Serum creatinine >2.5 mg/dL