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

September 5, 2019 updated by: Vijay Shah, M.D., Mayo Clinic

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Minnesota
      • Rochester, Minnesota, United States, 55905
        • Mayo Clinic in Rochester

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: F-652
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.
Drug: F-652
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The Number of Subjects With Unexpected Serious Adverse Events.
Time Frame: From day 1 up to 42 days following administration of last dose of study drug
The count of subjects who experience serious adverse events
From day 1 up to 42 days following administration of last dose of study drug

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Collaborators

Virginia Commonwealth University
Indiana University
Hennepin County Medical Center, Minneapolis

Investigators

  • Principal Investigator: Vijay Shah, MD, Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2016

Primary Completion (Actual)

June 30, 2018

Study Completion (Actual)

June 30, 2018

Study Registration Dates

First Submitted

January 7, 2016

First Submitted That Met QC Criteria

January 12, 2016

First Posted (Estimate)

January 14, 2016

Study Record Updates

Last Update Posted (Actual)

September 9, 2019

Last Update Submitted That Met QC Criteria

September 5, 2019

Last Verified

September 1, 2019

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 15-003249

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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