Clinical Trial: Use of F-652 in Patients With Alcoholic Hepatitis
Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional
Official Title: An Open-Label, Cohort Dose Escalation Study to Assess the Safety and Efficacy of F-652 in Patients With Alcoholic Hepatitis
Brief Summary:
Alcoholic hepatitis is a syndrome of progressive inflammatory liver injury associated with long-term heavy intake of ethanol. The pathogenesis is not completely understood. Patients who are severely affected present with subacute onset of fever, hepatomegaly, leukocytosis, marked impairment of liver function (e.g., jaundice, coagulopathy), and manifestations of portal hypertension (e.g., ascites, hepatic encephalopathy, variceal hemorrhage). However, milder forms of alcoholic hepatitis often do not cause any symptoms.
Alcoholic hepatitis usually persists and progresses to cirrhosis if heavy alcohol use continues. If alcohol use ceases, alcoholic hepatitis resolves slowly over weeks to months, sometimes without permanent sequelae but often with residual cirrhosis.
F-652 is a recombinant fusion protein containing human interleukin 22 (IL-22) and human Immunoglobulin G2 (IgG2)-Fc produced in CHO cells in serum-free culture. F-652 under development is intended to treat patients with graft vs host disease (GvHD) after bone marrow transplantation, and acute alcoholic hepatitis (AAH), a severe form of alcoholic liver disease (ALD). Both GvHD and AAH are diseases with unmet medical need. The current investigational new drug (IND) application is to conduct a phase Ia clinical study in GvHD patients to evaluate the safety and pharmacokinetic profile, and biomarkers of F-652 treatment by intravenous infusion (IV).
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.
Detailed Summary:
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.
Sponsor: Mayo Clinic
Current Primary Outcome: Absence of unexpected serious adverse events. [ Time Frame: Day 42 of study ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Total exposure (area under the curve) [ Time Frame: Day 42 of study ]
- Maximum serum concentration [ Time Frame: Day 42 of study ]
- Time at maximum serum concentration [ Time Frame: Day 42 of study ]
- Last measurable serum concentration [ Time Frame: Day 42 of study ]
- Time at last measurable serum concentration [ Time Frame: Day 42 of study ]
- Mean plasma clearance [ Time Frame: Day 42 of study ]
- Volume of distribution [ Time Frame: Day 42 of study ]
- Elimination half-life [ Time Frame: Day 42 of study ]
- Accumulation ratio [ Time Frame: Day 42 of study ]
- Dose proportionality [ Time Frame: Day 42 of study ]
Original Secondary Outcome: Same as current
Information By: Mayo Clinic
Dates:
Date Received: January 7, 2016
Date Started: February 2016
Date Completion: June 2018
Last Updated: November 9, 2016
Last Verified: November 2016
