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

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ClinicalTrials.gov Identifier: NCT02655510
Recruitment Status : Recruiting
First Posted : January 14, 2016
Last Update Posted : December 14, 2017
Sponsor:
Collaborators:
Indiana University
Virginia Commonwealth University
Hennepin County Medical Center, Minneapolis
Information provided by (Responsible Party):
Vijay Shah, M.D., Mayo Clinic

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.


Condition or disease Intervention/treatment Phase
Alcoholic Hepatitis Drug: F-652 Phase 1 Phase 2

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  (Clinical Trial)
Estimated Enrollment : 24 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-Label, Cohort Dose Escalation Study to Assess the Safety and Efficacy of F-652 in Patients With Alcoholic Hepatitis
Study Start Date : February 2016
Estimated Primary Completion Date : June 2018
Estimated Study Completion Date : June 2018

Resource links provided by the National Library of Medicine


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 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.
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.




Primary Outcome Measures :
  1. Absence of unexpected serious adverse events. [ Time Frame: Day 42 of study ]

Secondary Outcome Measures :
  1. Total exposure (area under the curve) [ Time Frame: Day 42 of study ]
  2. Maximum serum concentration [ Time Frame: Day 42 of study ]
  3. Time at maximum serum concentration [ Time Frame: Day 42 of study ]
  4. Last measurable serum concentration [ Time Frame: Day 42 of study ]
  5. Time at last measurable serum concentration [ Time Frame: Day 42 of study ]
  6. Mean plasma clearance [ Time Frame: Day 42 of study ]
  7. Volume of distribution [ Time Frame: Day 42 of study ]
  8. Elimination half-life [ Time Frame: Day 42 of study ]
  9. Accumulation ratio [ Time Frame: Day 42 of study ]
  10. Dose proportionality [ Time Frame: Day 42 of study ]

Other Outcome Measures:
  1. Change in Model for End Stage Liver Disease (MELD) score [ Time Frame: baseline, Day 42 of study ]
  2. Change in Lille Model for Alcoholic Hepatitis Score [ Time Frame: baseline, Day 42 of study ]
  3. Change in Triglycerides [ Time Frame: baseline, Day 42 of study ]
  4. Change in C-Reactive Protein (CRP) [ Time Frame: baseline, Day 42 of study ]
  5. Change in Aspartate Aminotransferase (AST) [ Time Frame: baseline, Day 42 of study ]
  6. Change in Alanine Aminotransferase (ALT) [ Time Frame: baseline, Day 42 of study ]
  7. Change in Serum Amyloid A1 (SAA1) [ Time Frame: baseline, Day 42 of study ]


Information from the National Library of Medicine

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Ages Eligible for Study:   21 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02655510


Contacts
Contact: Vijay Shah, MD 507-255-6028 shah.vijay@mayo.edu
Contact: Sarah Wilder, RN 507-284-2698 wilder.sarah@mayo.edu

Locations
United States, Minnesota
Mayo Clinic in Rochester Recruiting
Rochester, Minnesota, United States, 55905
Contact: Sarah Wilder, RN    507-284-2698    wilder.sarah@mayo.edu   
Sponsors and Collaborators
Mayo Clinic
Indiana University
Virginia Commonwealth University
Hennepin County Medical Center, Minneapolis
Investigators
Principal Investigator: Vijay Shah, MD Mayo Clinic

Responsible Party: Vijay Shah, M.D., PI, Mayo Clinic
ClinicalTrials.gov Identifier: NCT02655510     History of Changes
Other Study ID Numbers: 15-003249
First Posted: January 14, 2016    Key Record Dates
Last Update Posted: December 14, 2017
Last Verified: December 2017

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis, Alcoholic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Liver Diseases, Alcoholic
Alcohol-Induced Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders