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Use of F-652 in Patients With Alcoholic Hepatitis (TREAT 008)

Primary Purpose

Alcoholic Hepatitis

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
F-652
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alcoholic Hepatitis

Eligibility Criteria

21 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

3.1 Inclusion Criteria

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.

Exclusion Criteria

  1. Other or concomitant cause of liver disease as a result of:

    1. Autoimmune liver disease
    2. Wilson disease
    3. Vascular liver disease
    4. Drug induced liver disease Note: Concurrent viral hepatitis is not excluded.
  2. Co-infection with human immunodeficiency virus (HIV)
  3. 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.
  4. Active tuberculosis on chest x-ray at study entry
  5. 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
  6. Patients requiring the use of vasopressors or inotropic support
  7. Liver biopsy, if carried out, showing findings not compatible with alcoholic hepatitis
  8. 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.
  9. If female, known pregnancy, or has a positive urine or serum pregnancy test, or lactating/breastfeeding
  10. Serum creatinine >2.5 mg/dL

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

F-652

Arm Description

Participants will receive 10 μg/kg, 30 μg/kg or 45 μg/kg of F-652 on Day 1 and Day 7 via slow intravenous infusion. Three patients with MELD 11-20 will receive 10 μg/kg of F-652. Pharmacokinetic testing will be completed on these subjects. If evaluations demonstrate safety and efficacy signals, the next 3 patients will receive 30 μg/kg. If pharmacokinetic testing demonstrates safety and efficacy signals, the next 3 patients will receive 45 μg/kg. After demonstrating absence of side effects in this group, patients in MELD 21-28 will follow the same dose escalation regiment as the MELD 11-20 group.

Outcomes

Primary Outcome Measures

The Number of Subjects With Unexpected Serious Adverse Events.
The count of subjects who experience serious adverse events

Secondary Outcome Measures

Full Information

First Posted
January 7, 2016
Last Updated
September 5, 2019
Sponsor
Mayo Clinic
Collaborators
Indiana University, Virginia Commonwealth University, Hennepin County Medical Center, Minneapolis
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1. Study Identification

Unique Protocol Identification Number
NCT02655510
Brief Title
Use of F-652 in Patients With Alcoholic Hepatitis
Acronym
TREAT 008
Official Title
An Open-Label, Cohort Dose Escalation Study to Assess the Safety and Efficacy of F-652 in Patients With Alcoholic Hepatitis
Study Type
Interventional

2. Study Status

Record Verification Date
September 2019
Overall Recruitment Status
Completed
Study Start Date
February 2016 (undefined)
Primary Completion Date
June 30, 2018 (Actual)
Study Completion Date
June 30, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Indiana University, Virginia Commonwealth University, Hennepin County Medical Center, Minneapolis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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 Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alcoholic Hepatitis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Sequential Assignment
Model Description
A phase 2 dose escalating study was carried out. F-652 (10, 30 or 45 μg/kg) administered on day 1 and 7 was tested in 3 patients each with moderate (MELD scores: 11-20) and severe AH (MELD scores: 21-28).
Masking
None (Open Label)
Enrollment
18 (Actual)

8. Arms, Groups, and Interventions

Arm Title
F-652
Arm Type
Experimental
Arm Description
Participants will receive 10 μg/kg, 30 μg/kg or 45 μg/kg of F-652 on Day 1 and Day 7 via slow intravenous infusion. Three patients with MELD 11-20 will receive 10 μg/kg of F-652. Pharmacokinetic testing will be completed on these subjects. If evaluations demonstrate safety and efficacy signals, the next 3 patients will receive 30 μg/kg. If pharmacokinetic testing demonstrates safety and efficacy signals, the next 3 patients will receive 45 μg/kg. After demonstrating absence of side effects in this group, patients in MELD 21-28 will follow the same dose escalation regiment as the MELD 11-20 group.
Intervention Type
Drug
Intervention Name(s)
F-652
Intervention Description
Participants will receive 10 μg/kg, 30 μg/kg or 45 μg/kg of F-652 on Day 1 and Day 7 via slow intravenous infusion. Three patients will receive 10 μg/kg of F-652. Pharmacokinetic testing will be completed on these subjects. If evaluations demonstrate safety and efficacy signals, the next 3 patients will receive 30 μg/kg. If pharmacokinetic testing demonstrates safety and efficacy signals, the next 3 patients will receive 45 μg/kg.
Primary Outcome Measure Information:
Title
The Number of Subjects With Unexpected Serious Adverse Events.
Description
The count of subjects who experience serious adverse events
Time Frame
From day 1 up to 42 days following administration of last dose of study drug

10. Eligibility

Sex
All
Minimum Age & Unit of Time
21 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Vijay Shah, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
http://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Use of F-652 in Patients With Alcoholic Hepatitis

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