Use of F-652 in Patients With Alcoholic Hepatitis
| Status: | Completed |
|---|---|
| Conditions: | Hepatitis |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 21 - Any |
| Updated: | 8/18/2018 |
| Start Date: | February 2016 |
| End Date: | June 30, 2018 |
An Open-Label, Cohort Dose Escalation Study to Assess the Safety and Efficacy of F-652 in Patients With Alcoholic Hepatitis
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.
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.
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.
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.
To participate in this study, patients must meet all of the following criteria:
1. Able to provide written informed consent (either from patient or patient's legally
acceptable representative)
2. Male or female patients 21 years of age or older
3. Patients with alcoholic hepatitis defined as:
1. History of heavy alcohol abuse use: >40 g/day in females and >60 g/day in males
for a minimum period of 6 months
2. Consumed alcohol within 6 weeks of entry into the study
3. Serum bilirubin > 3mg/dL AND AST >ALT, but less than 500 U/L
4. MELD score between 11-28
5. 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).
4. Women of child-bearing potential must utilize appropriate birth control.
- Patients on steroids and/or pentoxifylline will not be excluded from the study.
We found this trial at
1
site
200 First Street SW
Rochester, Minnesota 55905
Rochester, Minnesota 55905
507-284-2511
Phone: 507-284-2698
Mayo Clinic Rochester Mayo Clinic is a nonprofit worldwide leader in medical care, research and...
Click here to add this to my saved trials
